AU2004235755A1

AU2004235755A1 - Nucleic acids and corresponding proteins entitled 109P1D4 useful in treatment and detection of cancer

Info

Publication number: AU2004235755A1
Application number: AU2004235755A
Authority: AU
Inventors: Pia M. Challita-Eid; Wangmao Ge; Aya Jakobovits; Steven B. Kanner; Juan J. Perez-Villar; Arthur B. Raitano
Original assignee: Agensys Inc
Current assignee: Agensys Inc
Priority date: 2003-04-30
Filing date: 2004-04-30
Publication date: 2004-11-18
Also published as: JP2007525183A; AU2008212020B2; EP1622571A4; CA2522994C; WO2004098515A3; EP1622571A2; CA2522994A1; AU2008212020A1; WO2004098515A2; JP2011152132A

Description

WO 2004/098515 PCT/US2004/013568 1 NUCLEIC ACIDS AND CORRESPONDING PROTEINS ENTITLED 109P1D4 USEFUL IN TREATMENT AND DETECTION OF CANCER STATEMENT OF RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH Not applicable. FIELD OF THE INVENTION The invention described herein relates to genes and their encoded proteins, termed 109P1 D4 and variants thereof, expressed in certain cancers, and to diagnostic and therapeutic methods and compositions useful in the management of cancers that express 109P1 D4. BACKGROUND OF THE INVENTION Cancer is the second leading cause of human death next to coronary disease. Worldwide, millions of people die from cancer every year. In the United States alone, as reported by the American Cancer Society, cancer causes the death of well over a half-million people annually, with over 1.2 million new cases diagnosed per year. While deaths from heart disease have been declining significantly, those resulting from cancer generally are on the rise. In the early part of the next century, cancer is predicted to become the leading cause of death. Worldwide, several cancers stand out as the leading killers. In particular, carcinomas of the lung, prostate, breast, colon, pancreas, and ovary represent the primary causes of cancer death. These and virtually all other carcinomas share a common lethal feature. With very few exceptions, metastatic disease from a carcinoma is fatal. Moreover, even for those cancer patients who initially survive their primary cancers, common experience has shown that their lives are dramatically altered. Many cancer patients experience strong anxieties driven by the awareness of the potential for recurrence or treatment failure. Many cancer patients experience physical debilitations following treatment. Furthermore, many cancer patients experience a recurrence. Worldwide, prostate cancer is the fourth most prevalent cancer in men. In North America and Northern Europe, it is by far the most common cancer in males and is the second leading cause of cancer death in men. In the United States alone, well over 30,000 men die annually of this disease - second only to lung cancer. Despite the magnitude of these figures, there is still no effective treatment for metastatic prostate cancer. Surgical prostatectomy, radiation therapy, hormone ablation therapy, surgical castration and chemotherapy continue to be the main treatment modalities. Unfortunately, these treatments are ineffective for many and are often associated with undesirable consequences. On the diagnostic front, the lack of a prostate tumor marker that can accurately detect early-stage, localized tumors remains a significant limitation in the diagnosis and management of this disease. Although the serum prostate specific antigen (PSA) assay has been a very useful tool, however its specificity and general utility is widely regarded as lacking in several important respects.

WO 2004/098515 PCT/US2004/013568 2 Progress in identifying additional specific markers for prostate cancer has been improved by the generation of prostate cancer xenografts that can recapitulate different stages of the disease in mice. The LAPC (Los Angeles Prostate Cancer) xenografts are prostate cancer xenografts that have survived passage in severe combined immune deficient (SCID) mice and have exhibited the capacity to mimic the transition from androgen dependence to androgen independence (Klein et al., 1997, Nat. Med. 3:402). More recently identified prostate cancer markers include PCTA-1 (Su et al., 1996, Proc. Nati. Acad. Sci. USA 93: 7252), prostate-specific membrane (PSM) antigen (Pinto et al., Clin Cancer Res 1996 Sep 2 (9): 1445 51), STEAP (Hubert, et al., Proc Natl Acad Sci U S A. 1999 Dec 7; 96(25): 14523-8) and prostate stem cell antigen (PSCA) (Reiter et al., 1998, Proc. Nat. Acad. Sci. USA 95: 1735). While previously identified markers such as PSA, PSM, PCTA and PSCA have facilitated efforts to diagnose and treat prostate cancer, there is need for the identification of additional markers and therapeutic targets for prostate and related cancers in order to further improve diagnosis and therapy. Renal cell carcinoma (RCC) accounts for approximately 3 percent of adult malignancies. Once adenomas reach a diameter of 2 to 3 cm, malignant potential exists. In the adult, the two principal malignant renal tumors are renal cell adenocarcinoma and transitional cell carcinoma of the renal pelvis or ureter. The incidence of renal cell adenocarcinoma is estimated at more than 29,000 cases in the United States, and more than 11,600 patients died of this disease in 1998. Transitional cell carcinoma is less frequent, with an incidence of approximately 500 cases per year in the United States. Surgery has been the primary therapy for renal cell adenocarcinoma for many decades. Until recently, metastatic disease has been refractory to any systemic therapy. With recent developments in systemic therapies, particularly immunotherapies, metastatic renal cell carcinoma may be approached aggressively in appropriate patients with a possibility of durable responses. Nevertheless, there is a remaining need for effective therapies for these patients. Of all new cases of cancer in the United States, bladder cancer represents approximately 5 percent in men (fifth most common neoplasm) and 3 percent in women (eighth most common neoplasm). The incidence is increasing slowly, concurrent with an increasing older population. In 1998, there was an estimated 54,500 cases, including 39,500 in men and 15,000 in women. The age-adjusted incidence in the United States is 32 per 100,000 for men and eight per 100,000 in women. The historic malelfemale ratio of 3:1 may be decreasing related to smoking patterns in women. There were an estimated 11,000 deaths from bladder cancer in 1998 (7,800 in men and 3,900 in women). Bladder cancer incidence and mortality strongly increase with age and will be an increasing problem as the population becomes more elderly. Most bladder cancers recur in the bladder. Bladder cancer is managed with a combination of transurethral resection of the bladder (TUR) and intravesical chemotherapy or immunotherapy. The multifocal and recurrent nature of bladder cancer points out the limitations of TUR. Most muscle-invasive cancers are not cured by TUR alone. Radical cystectomy and urinary diversion is the most effective means to eliminate the cancer but carry an undeniable impact on urinary and sexual function. There continues to be a significant need for treatment modalities that are beneficial for bladder cancer patients. An estimated 130,200 cases of colorectal cancer occurred in 2000 in the United States, including 93,800 cases of colon cancer and 36,400 of rectal cancer. Colorectal cancers are the third most common cancers in men and women. Incidence rates declined significantly during 1992-1996 (-2.1% per year). Research suggests that these declines have been due to increased screening and polyp removal, preventing progression of polyps to invasive cancers. There were an estimated 56,300 deaths (47,700 from colon cancer, 8,600 from rectal cancer) in 2000, accounting for about 11% of all U.S. cancer deaths. At present, surgery is the most common form of therapy for colorectal cancer, and for cancers that have not spread, it is frequently curative. Chemotherapy, or chemotherapy plus radiation, is given before or after surgery to most WO 2004/098515 PCT/US2004/013568 3 patients whose cancer has deeply perforated the bowel wall or has spread to the lymph nodes. A permanent colostomy (creation of an abdominal opening for elimination of body wastes) is occasionally needed for colon cancer and is infrequently required for rectal cancer. There continues to be a need for effective diagnostic and treatment modalities for colorectal cancer. There were an estimated 164,100 new cases of lung and bronchial cancer in 2000, accounting for 14% of all U.S. cancer diagnoses. The incidence rate of lung and bronchial cancer is declining significantly in men, from a high of 86.5 per 100,000 in 1984 to 70.0 in 1996. In the 1990s, the rate of increase among women began to slow. In 1996, the incidence rate in women was 42.3 per 100,000. Lung and bronchial cancer caused an estimated 156,900 deaths in 2000, accounting for 28% of all cancer deaths. During 1992-1996, mortality from lung cancer declined significantly among men (-1.7% per year) while rates for women were still significantly increasing (0.9% per year). Since 1987, more women have died each year of lung cancer than breast cancer, which, for over 40 years, was the major cause of cancer death in women. Decreasing lung cancer incidence and mortality rates most likely resulted from decreased smoking rates over the previous 30 years; however, decreasing smoking patterns among women lag behind those of men. Of concern, although the declines in adult tobacco use have slowed, tobacco use in youth is increasing again. Treatment options for lung and bronchial cancer are determined by the type and stage of the cancer and include surgery, radiation therapy, and chemotherapy. For many localized cancers, surgery is usually the treatment of choice. Because the disease has usually spread by the time it is discovered, radiation therapy and chemotherapy are often needed in combination with surgery. Chemotherapy alone or combined with radiation is the treatment of choice for small cell lung cancer; on this regimen, a large percentage of patients experience remission, which in some cases is long lasting. There is however, an ongoing need for effective treatment and diagnostic approaches for lung and bronchial cancers. An estimated 182,800 new invasive cases of breast cancer were expected to occur among women in the United States during 2000. Additionally, about 1,400 new cases of breast cancer were expected to be diagnosed in men in 2000. After increasing about 4% per year in the 1980s, breast cancer incidence rates in women have leveled off in the 1990s to about 110.6 cases per 100,000. In the U.S. alone, there were an estimated 41,200 deaths (40,800 women, 400 men) in 2000 due to breast cancer. Breast cancer ranks second among cancer deaths in women. According to the most recent data, mortality rates declined significantly during 1992-1996 with the largest decreases in younger women, both white and black. These decreases were probably the result of earlier detection and improved treatment. Taking into account the medical circumstances and the patient's preferences, treatment of breast cancer may involve lumpectomy (local removal of the tumor) and removal of the lymph nodes under the arm; mastectomy (surgical removal of the breast) and removal of the lymph nodes under the arm; radiation therapy; chemotherapy; or hormone therapy. Often, two or more methods are used in combination. Numerous studies have shown that, for early stage disease, long-term survival rates after lumpectomy plus radiotherapy are similar to survival rates after modified radical mastectomy. Significant advances in reconstruction techniques provide several options for breast reconstruction after mastectomy. Recently, such reconstruction has been done at the same time as the mastectomy. Local excision of ductal carcinoma in situ (DCIS) with adequate amounts of surrounding normal breast tissue may prevent the local recurrence of the DCIS. Radiation to the breast and/or tamoxifen may reduce the chance of DCIS occurring in the remaining breast tissue. This is important because DCIS, if left untreated, may develop into invasive breast cancer. Nevertheless, there are serious side effects or sequelae to these treatments. There is, therefore, a need for efficacious breast cancer treatments. 3 WO 2004/098515 PCT/US2004/013568 4 There were an estimated 23,100 new cases of ovarian cancer in the United States in 2000. It accounts for 4% of all cancers among women and ranks second among gynecologic cancers. During 1992-1996, ovarian cancer incidence rates were significantly declining. Consequent to ovarian cancer, there were an estimated 14,000 deaths in 2000, Ovarian cancer causes more deaths than any other cancer of the female reproductive system. Surgery, radiation therapy, and chemotherapy are treatment options for ovarian cancer. Surgery usually includes the removal of one or both ovaries, the fallopian tubes (salpingo-oophorectomy), and the uterus (hysterectomy). In some very early tumors, only the involved ovary will be removed, especially in young women who wish to have children. In advanced disease, an attempt is made to remove all intra-abdominal disease to enhance the effect of chemotherapy. There continues to be an important need for effective treatment options for ovarian cancer. There were an estimated 28,300 new cases of pancreatic cancer in the United States in 2000. Over the past 20 years, rates of pancreatic cancer have declined in men. Rates among women have remained approximately constant but may be beginning to decline. Pancreatic cancer caused an estimated 28,200 deaths in 2000 in the United States. Over the past 20 years, there has been a slight but significant decrease in mortality rates among men (about -0.9% per year) while rates have increased slightly among women. Surgery, radiation therapy, and chemotherapy are treatment options for pancreatic cancer. These treatment options can extend survival and/or relieve symptoms in many patients but are not likely to produce a cure for most. There is a significant need for additional therapeutic and diagnostic options for pancreatic cancer. SUMMARY OF THE INVENTION The present invention relates to a gene, designated 109P1 D4, that has now been found to be over-expressed in the cancer(s) listed in Table I. Northern blot expression analysis of 109P1D4 gene expression in normal tissues shows a restricted expression pattern in adult tissues. The nucleotide (Figure 2) and amino acid (Figure 2, and Figure 3) sequences of 109P1D4 are provided. The tissue-related profile of 109P1D4 in normal adult tissues, combined with the over-expression observed in the tissues listed in Table I, shows that 109P1 D4 is aberrantly over-expressed in at least some cancers, and thus serves as a useful diagnostic, prophylactic, prognostic, and/or therapeutic target for cancers of the tissue(s) such as those listed in Table I. The invention provides polynucleotides corresponding or complementary to all or part of the 109P1 D4 genes, mRNAs, and/or coding sequences, preferably in isolated form, including polynucleotides encoding 109PI D4-related proteins and fragments of 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or more than 25 contiguous amino acids; at least 30, 35, 40, 45, 50, 55, 60, 65, 70, 80, 85, 90, 95, 100 or more than 100 contiguous amino acids of a 109P1D4-related protein, as well as the peptides/proteins themselves; DNA, RNA, DNA/RNA hybrids, and related molecules, polynucleotides or oligonucleotides complementary or having at least a 90% homology to the 109P1 D4 genes or mRNA sequences or parts thereof, and polynucleotides or oligonucleotides that hybridize to the 109P1 D4 genes, mRNAs, or to 109P1 D4-encoding polynucleotides. Also provided are means for isolating cDNAs and the genes encoding 109P1 D4. Recombinant DNA molecules containing 109P1 D4 polynucleotides, cells transformed or transduced with such molecules, and host-vector systems for the expression of 109P1D4 gene products are also provided. The invention further provides antibodies that bind to 109P1 D4 proteins and polypeptide fragments thereof, including polyclonal and monoclonal antibodies, murine and other mammalian antibodies, chimeric antibodies, humanized and fully human antibodies, and antibodies labeled with a detectable marker or therapeutic agent. In certain embodiments, there is a proviso that the entire nucleic acid sequence of Figure 2 is not encoded and/or the entire amino acid sequence of Figure 2 is not prepared. In certain embodiments, the entire nucleic acid sequence of Figure 2 is encoded and/or the entire amino acid sequence of Figure 2 is prepared, either of which are in respective human unit dose forms.

WO 2004/098515 PCT/US2004/013568 5 The invention further provides methods for detecting the presence and status of 109P1 D4 polynucleotides and proteins in various biological samples, as well as methods for identifying cells that express 109P1 D4. A typical embodiment of this invention provides methods for monitoring 109P1 D4 gene products in a tissue or hematology sample having or suspected of having some form of growth dysregulation such as cancer. The invention further provides various immunogenic or therapeutic compositions and strategies for treating cancers that express 109P1D4 such as cancers of tissues listed in Table I, including therapies aimed at inhibiting the transcription, translation, processing or function of 109P1 D4 as well as cancer vaccines. In one aspect, the invention provides compositions, and methods comprising them, for treating a cancer that expresses 109P1 D4 in a human subject wherein the composition comprises a carrier suitable for human use and a human unit dose of one or more than one agent that inhibits the production or function of 109P1 D4. Preferably, the carrier is a uniquely human carrier. In another aspect of the invention, the agent is a moiety that is immunoreactive with 109P1D4 protein. Non-limiting examples of such moieties include, but are not limited to, antibodies (such as single chain, monoclonal, polyclonal, humanized, chimeric, or human antibodies), functional equivalents thereof (whether naturally occurring or synthetic), and combinations thereof. The antibodies can be conjugated to a diagnostic or therapeutic moiety. In another aspect, the agent is a small molecule as defined herein. In another aspect, the agent comprises one or more than one peptide which comprises a cytotoxic T lymphocyte (CTL) epitope that binds an HLA class I molecule in a human to elicit a CTL response to 109P1 D4 and/or one or more than one peptide which comprises a helper T lymphocyte (HTL) epitope which binds an HLA class Il molecule in a human to elicit an HTL response. The peptides of the invention may be on the same or on one or more separate polypeptide molecules. In a further aspect of the invention, the agent comprises one or more than one nucleic acid molecule that expresses one or more than one of the CTL or HTL response stimulating peptides as described above. In yet another aspect of the invention, the one or more than one nucleic acid molecule may express a moiety that is immunologically reactive with 109P1 D4 as described above. The one or more than one nucleic acid molecule may also be, or encodes, a molecule that inhibits production of 109P1D4. Non-limiting examples of such molecules include, but are not limited to, those complementary to a nucleotide sequence essential for production of 109P1 D4 (e.g. antisense sequences or molecules that form a triple helix with a nucleotide double helix essential for 109P1D4 production) or a ribozyme effective to lyse 109P1D4 mRNA. Note that to determine the starting position of any peptide set forth in Tables VIll-XXI and XXII to XLIX (collectively HLA Peptide Tables) respective to its parental protein, e.g., variant 1, variant 2, etc., reference is made to three factors: the particular variant, the length of the peptide in an HLA Peptide Table, and the Search Peptides in Table VII. Generally, a unique Search Peptide is used to obtain HLA peptides of a particular for a particular variant. The position of each Search Peptide relative to its respective parent molecule is listed in Table VII. Accordingly, if a Search Peptide begins at position "X", one must add the value "X - 1" to each position in Tables VIII-XXI and XXII to XLIX to obtain the actual position of the HLA peptides in their parental molecule. For example, if a particular Search Peptide begins at position 150 of its parental molecule, one must add 150 -1, i.e., 149 to each HLA peptide amino acid position to calculate the position of that amino acid in the parent molecule. One embodiment of the invention comprises an HLA peptide, that occurs at least twice in Tables VIII-XXI and XXII to XLIX collectively, or an oligonucleotide that encodes the HLA peptide. Another embodiment of the invention comprises an HLA peptide that occurs at least once in Tables VIII-XXI and at least once in tables XXII to XLIX, or an oligonucleotide that encodes the HLA peptide. Another embodiment of the invention is antibody epitopes, which comprise a peptide regions, or an oligonucleotide encoding the peptide region, that has one two, three, four, or five of the following characteristics: WO 2004/098515 PCT/US2004/013568 6 i) a peptide region of at least 5 amino acids of a particular peptide of Figure 3, in any whole number increment up to the full length of that protein in Figure 3, that includes an amino acid position having a value equal to or greater than 0.5, 0.6, 0.7, 0.8, 0.9, or having a value equal to 1.0, in the Hydrophilicity profile of Figure 5; ii) a peptide region of at least 5 amino acids of a particular peptide of Figure 3, in any whole number increment up to the full length of that protein in Figure 3, that includes an amino acid position having a value equal to or less than 0.5, 0.4, 0.3, 0.2, 0.1, or having a value equal to 0.0, in the Hydropathicity profile of Figure 6; iii) a peptide region of at least 5 amino acids of a particular peptide of Figure 3, in any whole number increment up to the full length of that protein in Figure 3, that includes an amino acid position having a value equal to or greater than 0.5, 0.6, 0.7, 0.8, 0.9, or having a value equal to 1.0, in the Percent Accessible Residues profile of Figure 7; iv) a peptide region of at least 5 amino acids of a particular peptide of Figure 3, in any whole number increment up to the full length of that protein in Figure 3, that includes an amino acid position having a value equal to or greater than 0.5, 0.6, 0.7, 0.8, 0.9, or having a value equal to 1.0, in the Average Flexibility profile of Figure 8; or v) a peptide region of at least 5 amino acids of a particular peptide of Figure 3, in any whole number increment up to the full length of that protein in Figure 3, that includes an amino acid position having a value equal to or greater than 0.5, 0.6, 0.7, 0.8, 0.9, or having a value equal to 1.0, in the Beta-turn profile of Figure 9. BRIEF DESCRIPTION OF THE FIGURES Figure 1. The 109P1 D4 SSH sequence of 192 nucleotides. Figure 2. A) The cDNA and amino acid sequence of 109P1D4 variant 1 (also called 109P1D4 v.1" or "109P1D4 variant 1") is shown in Figure 2A, The start methionine is underlined. The open reading frame extends from nucleic acid 846-3911 including the stop codon. B) The cDNA and amino acid sequence of 109P1D4 variant 2 (also called "109P1D4 v.2") is shown in Figure 2B. The codon for the start methionine is underlined. The open reading frame extends from nucleic acid 503-3667 including the stop codon. C) The cDNA and amino acid sequence of 109P1 D4 variant 3 (also called "1 09P1 D4 v.3") is shown in Figure 2C. The codon for the start methionine is underlined. The open reading frame extends from nucleic acid 846-4889 including the stop codon. D) The cDNA and amino acid sequence of 109P1 D4 variant 4 (also called "1 09P1 D4 v.4") is shown in Figure 2D. The codon for the start methionine is underlined. The open reading frame extends from nucleic acid 846-4859 including the stop codon. E) The cDNA and amino acid sequence of 109P1D4 variant 5 (also called "109P1D4 v.5") is shown in Figure 2E. The codon for the start methionine is underlined. The open reading frame extends from nucleic acid 846-4778 including the stop codon. F) The cDNA and amino acid sequence of 109P1D4 variant 6 (also called "109P1D4 v.6") is shown in Figure 2F. The codon for the start methionine is underlined. The open reading frame extends from nucleic acid 614-3727 including the stop codon. G) The cDNA and amino acid sequence of 109P1 D4 variant 7 (also called "1 09PI D4 v.7") is shown in Figure 2G. The codon for the start methionine is underlined. The open reading frame extends from nucleic acid 735-3881 including the stop codon. H) The cDNA and amino acid sequence of 109P1D4 variant 8 (also called "1 09P1 D4 v.8") is shown in Figure 2H. The codon for the start methionine is underlined. The open reading frame extends from nucleic acid 735-4757 including the stop codon.

WO 2004/098515 PCT/US2004/013568 7 I) The cDNA and amino acid sequence of 109P1D4 variant 9 (also called "1 09P1D4 v.9") is shown in Figure 21. The codon for the start methionine is underlined. The open reading frame extends from nucleic acid 514-3627 including the stop codon. J) 109PID4 v.1, v.2 and v.3 SNP variants. Though these SNP variants are shown separately, they can also occur in any combinations and in any of the transcript variants listed above. K) IO9PID4 v.6, v.7 and v.8 SNP variants. Though these SNP variants are shown separately, they can also occur in ar combinations and in any of the transcript variants listed above. Figure 3. A) The amino acid sequence of 109P1D4 v.1 is shown in Figure 3A; it has 1021 amino acids. B) The amino acid sequence of 109P1D4 v.2 is shown in Figure 3B; it has 1054 amino acids. C) The amino acid sequence of 109P1D4 v.3 is shown in Figure 3C; it has 1347 amino acids. D) The amino acid sequence of 109P1D4 v.4 is shown in Figure 3D; it has 1337 amino acids. E) The amino acid sequence of 109P1D4 v.5 is shown in Figure 3E; it has 1310 amino acids. F) The amino acid sequence of 109P1D4 v.6 is shown in Figure 3F; it has 1037 amino acids. G) The amino acid sequence of 109P1D4 v.7 is shown in Figure 3G; it has 1048 amino acids. H) The amino acid sequence of 109P1D4 v.8 is shown in Figure 3H; it has 1340 amino acids. 1) The amino acid sequence of 109P1D4 v.9 is shown in Figure 31; it has 1037 amino acids. As used herein, a reference to 109P1D4 includes all variants thereof, including those shown in Figures 2, 3, 10, 11, and 12 unless the context clearly indicates otherwise. Figure 4. Alignment of 109P1D4 v.1 Protein with protocadherin-1 1. Figure 5. Hydrophilicity amino acid profile of 109P1D4 v.1-v.9 determined by computer algorithm sequence analysis using the method of Hopp and Woods (Hopp T.P, Woods K.R., 1981. Proc. Natl. Acad. Sci. U.S.A. 78:3824-3828) accessed on the Protscale website located on the World Wide Web at (expasy.ch/cgi-bin/protscale.pl) through the ExPasy molecular biology server, Figure 6. Hydropathicity amino acid profile of 109P1D4 v.1-v.9 determined by computer algorithm sequence analysis using the method of Kyte and Doolittle (Kyte J., Doolittle R.F., 1982. J. Mol. Biol. 157:105-132) accessed on the ProtScale website located on the World Wide Web at (.expasy.ch/cgi-bin/protscale.pl) through the ExPasy molecular biology server. Figure 7. Percent accessible residues amino acid profile of 109P1D4 v.1-v.9 determined by computer algorithm sequence analysis using the method of Janin (Janin J., 1979 Nature 277:491-492) accessed on the ProtScale website located on the World Wide Web at (.expasy.ch/cgi-bin/protscale.pl) through the ExPasy molecular biology server. Figure 8. Average flexibility amino acid profile of 109P1D4 v.1-v.9 determined by computer algorithm sequence analysis using the method of Bhaskaran and Ponnuswamy (Bhaskaran R., and Ponnuswamy P.K., 1988. Int. J. Pept. Protein Res. 32:242-255) accessed on the ProtScale website located on the World Wide Web at (.expasy.ch/cgi-bin/protscale.pl) through the ExPasy molecular biology server. Figure 9. Beta-turn amino acid profile of 109P1D4 v.1-v.9 determined by computer algorithm sequence analysis using the method of Deleage and Roux (Deleage, G., Roux B. 1987 Protein Engineering 1:289-294) accessed on the ProtScale website located on the World Wide Web at (.expasy.chlcgi-bin/protscale.pl) through the ExPasy molecular biology server. Figure 10. Structure of transcript variants of 109P1D4. Variants 109P1D4 v.2 through v.9 were transcript variants of v.1. Variant v.2 shared middle portion of v.1 sequence (the 3' portion of exon I and 5' portion of exon 2). Variant WO 2004/098515 PCT/US2004/013568 8 v.6 was similar to v.2 but added an extra exon between exons 1 and 2 of v.2. V.3 shared exon 1 and 5' portion of exon 2 with v.1 with five additional exons downstream. Compared with v.3, v.4 deleted exon 4 of v.3 while v.5 deleted exons 3 and 4 of v.3. Variant v.5 lacked exons 3 and 4. This gene (called PCD11) is located in sex chromosomes X and Y. Ends of exons in the transcripts are marked above the boxes. Potential exons of this gene are shown in order as on the human genome. Poly A tails and single nucleotide differences are not shown in the figure. Lengths of introns and exons are not proportional. Figure I. Schematic alignment of protein variants of 109P1D4. Variants 109P1D4 v.2 through v.9 were proteins translated from the corresponding transcript variants. All these protein variants shared a common portion of the sequence, i.e., 3-1011 of v.1, except for a few amino acids different in this segment resulted from SNP in the transcripts. Variant v.6 and v.9 were the same except for two amino acids at 906 and 1001. Variant v.8 was almost the same as v.5, except for the N-terminal end, and a 2-aa deletion at 1117-8. Single amino acid difference was not shown. Numbers in parentheses corresponded to positions in variant v.3. Figure 12. Intentionally Omitted. Figure 13. Figures 13(a)-(i): Secondary structure and transmembrane domains prediction for 109P1D4 protein variants 1-9 (v.1 - (SEQ ID NO: 31); v.2 - (SEQ ID NO: 32); v.3 - (SEQ ID NO: 33); v.4 - (SEQ ID NO: 34); v.5 - (SEQ ID NO: 35); v.6 - (SEQ ID NO: 36); v.7 - (SEQ ID NO: 37); v.8 - (SEQ ID NO: 38); v.9 - (SEQ ID NO: 39)). The secondary structures of 109P1D4 protein variants were predicted using the HNN - Hierarchical Neural Network method (NPS@: Network Protein Sequence Analysis TIBS 2000 March Vol. 25, No 3 [291]:147-150 Combet C., Blanchet C., Geourjon C. and Deleage G., http://pbi.ibcp.fr/cgi-bin/npsaautomat.pl?page=npsa-nn.html), accessed from the ExPasy molecular biology server located on the World Wide Web at (.expasy.ch/tools/). This method predicts the presence and location of alpha helices, extended strands, and random coils from the primary protein sequence. The percent of the protein variant in a given secondary structure is also listed. Figures 13(J)-(R) top panels: Schematic representation of the probability of existence of transmembrane regions of 109P1 D4 variants based on the TMpred algorithm of Hofmann and Stoffel which utilizes TMBASE (K. Hofmann, W. Stoffel. TMBASE -A database of membrane spanning protein segments Biol. Chem. Hoppe-Seyler 374:166, 1993). Figures 13(J)-(R) bottom panels: Schematic representation of the probability of the existence of transmembrane regions of 109P1 D4 variants based on the TMHMM algorithm of Sonnhammer, von Heijne, and Krogh (Erik L.L. Sonnhammer, Gunnar von Heijne, and Anders Krogh: A hidden Markov model for predicting transmembrane helices in protein sequences. In Proc. of Sixth Int. Conf. on Intelligent Systems for Molecular Biology, p 175-182 Ed J. Glasgow, T. Littlejohn, F. Major, R. Lathrop, D. Sankoff, and C. Sensen Menlo Park, CA: AAAl Press, 1998). The TMpred and TMHMM algorithms are accessed from the ExPasy molecular biology server located on the World Wide Web at (.expasy.ch/tools/). Figure 14. Expression of 109P1D4 in Lymphoma Cancer Patient Specimens. RNA was extracted from peripheral blood lymphocytes, cord blood isolated from normal individuals, and from lymphoma patient cancer specimens. Northem blots with I Opg of total RNA were probed with the 109P1 D4 sequence. Size standards in kilobases are on the side. Results show expression of 109P1 D4 in lymphoma patient specimens but not in the normal blood cells tested. Figure 15. Expression of 109P1D4 by RT-PCR. First strand cDNA was prepared from vital pool I (liver, lung and kidney), vital pooi 2 (pancreas, colon and stomach), prostate cancer pool, bladder cancer pool, kidney cancer pool, colon cancer pool, lung cancer pool, ovary cancer pool, breast cancer pool, cancer metastasis pool, and pancreas cancer pool. Normalization was performed by PCR using primers to actin and GAPDH. Semi-quantitative PCR, using primers to 109P1 D4, was performed at 30 cycles of amplification. Results show strong expression of 109P1 D4 in all cancer pools tested. Very low expression was detected in the vital pools. Figure 16. Expression of 109P1D4 in normal tissues. Two multiple tissue northern blots (Clontech), both with 2 pg of mRNMane, were probed with the 1 09P1 D4 SSH fragment. Size standards in kilobases (kb) are indicated on the side.

WO 2004/098515 PCT/US2004/013568 9 Results show expression of approximately 10 kb 109P1D4 transcript in ovary. Weak expression was also detected in placenta and brain, but not in the other normal tissues tested. Figure 17. Expression of 109P1D4 in human cancer cell lines. RNA was extracted from a number of human prostate and bone cancer cell lines. Northern blots with 10 pg of total RNA/lane were probed with the 109P1 D4 SSH fragment. Size standards in kilobases (kb) are indicated on the side. Results show expression of 109P1D4 in LAPC-9AD, LAPC-9Al, LNCaP prostate cancer cell lines, and in the bone cancer cell lines, SK-ES-1 and RD-ES. Figure 18. Figure IBA: 109P1D4 Expression in Human Normal Tissues. An cDNA dot blot containing 76 different samples from human tissues was analyzed using a 109P1D4 SSH probe. Expression was only detected in multiple areas of the brain, placenta, ovary, and fetal brain, amongst all tissues tested. Figure 181B: Expression of 109PIlD4 in patient cancer specimens. Expression of 109P1 D4 was assayed in a panel of human cancers (T) and their respective matched normal tissues (N) on RNA dot blots. Upregulated expression of 109P1 D4 in tumors compared to normal tissues was observed in uterus, lung and stomach. The expression detected in normal adjacent tissues (isolated from diseased tissues) but not in normal tissues (isolated from healthy donors) may indicate that these tissues are not fully normal and that 109P1 D4 may be expressed in early stage tumors. Figure 19. 109P1 D4 Expression in Lung Cancer Patient Specimens. RNA was extracted from normal lung, prostate cancer xenograft LAPC-9AD, bone cancer cell line RD-ES, and lung cancer patient tumors. Northern blots with 10 pg of total RNA were probed with 109P1D4. Size standards in kilobases are on the side. Results show strong expression of 109P1 D4 in lung tumor tissues as well as the RD-ES cell line, but not in normal lung. Figure 20. Expression of soluble secreted Tag5 109P1D4 in 293T cells. 293T cells were transfected with either an empty vector or with the Tag5 secretion vector encoding the extracellular domain (ECD; amino acids 24-812) of 109P1 D4 variant I fused to a Myc/His epitope Tag. 2 days later, cells and media harvested and analyzed for expression of the recombinant Tag5 109P1D4 protein by SDS-PAGE followed by anti-His epitope tag Western blotting. An arrow indicates the immunoreactive band corresponding to the 109P1D4 ECD present in the media and the lysate from Tag5 109P1D4 transfected cells. Figure 21. Expression of 109P1D4 protein in 293T cells. 293T cells were transfected with either an empty vector or with pCDNA3.1 vector encoding the full length cDNA of 109P1 D4 variant 1 fused to a MyclHis epitope Tag. 2 days later, cells were harvested and analyzed for expression of 109P1D4 variant I protein by SDS-PAGE followed by anti-His epitope tag Western blotting. An arrow indicates the immunoreactive band corresponding to the full length 109P1D4 variant I protein expressed in cells transfected with the 109P1 D4 vector but not in control cells. Figure 22. Tyrosine phosphorylation of 109P1D4 after pervanadate treatment. 293T cells were transfected with the neomycin resistance gene alone or with 109P1 D4 in pSRp vector. Twenty four hours after transfection, the cells were either left in 10% serum or grown in 0.1% serum overnight. The cells were then left untreated or were treated with 200 pM pervanadate (1:1 mixture of Na3VO4 and H202) for 30 minutes. The cells were lysed in Triton X-1 00, and the 109P1 D4 protein was immunoprecipitated with anti-His monoclonal antibody. The immunoprecipitates were run on SDS-PAGE and then Westem blotted with either anti-phosphotyrosine (upper panel) or anti-His (lower panel). The 109PI D4 protein is phosphorylated on tyrosine in response to pervanadate treatment, and a large amount of the protein moves to the insoluble fraction following pervanadate-induced activation. Figure 23. Effect of 109P1 D4 RNAi on cell proliferation. LNCaP cells were transfected with Lipofectamine 2000 alone or with siRNA oligonucleotides. The siRNA oligonucleotides included a negative control, Luc4, specific for Luciferase, a positive control, Eg5, specific for the mitotic spindle protein Eg5, or three siRNAs specific for the 109P1D4 protein, 109P1D4.a, 109P1D4.c and 109P1D4.d at 20 nM concentration. Twenty four hours after transfection, the cells were pulsed WO 2004/098515 PCT/US2004/013568 10 with 3 H-thymidine and incorporation was measured after 72 hours. All three siRNAs to 109P1 D4 inhibited the proliferation of LNCaP cells, indicating that 109P1D4 expression is important for the cell growth pathway of these cancer cells. DETAILED DESCRIPTION OF THE INVENTION Outline of Sections 1.) Definitions 11.) 109P1D4 Polynucleotides ll.A.) Uses of 109P1D4 Polynucleotides IL.A.i.) Monitoring of Genetic Abnormalities II.A.2.) Antisense Embodiments II.A.3.) Primers and Primer Pairs lI.A.4.) Isolation of 109PiD4-Encoding Nucleic Acid Molecules IlA.5.) Recombinant Nucleic Acid Molecules and Host-Vector Systems iII.) 109P1D4-related Proteins IlI.A.) Motif-bearing Protein Embodiments IIlB.) Expression of 109P1D4-related Proteins IIlC.) Modifications of 109P1D4-related Proteins Ill.D.) Uses of 109P1D4-related Proteins IV.) 109P1D4 Antibodies V.) 109P1D4 Cellular Immune Responses VI.) 109P104 Transgenic Animals VII.) Methods for the Detection of 109P1 D4 Vill.) Methods for Monitoring the Status of 109P1D4-related Genes and Their Products IX.) Identification of Molecules That Interact With 109P1D4 X.) Therapeutic Methods and Compositions X.A.) Anti-Cancer Vaccines X.B.) 109P1 D4 as a Target for Antibody-Based Therapy X.C.) 109P1D4 as a Target for Cellular Immune Responses X.C.1. Minigene Vaccines X.C.2. Combinations of CTL Peptides with Helper Peptides X.C.3. Combinations of CTL Peptides with T Cell Priming Agents X.C.4. Vaccine Compositions Comprising DC Pulsed with CTL and/or HTL Peptides X.D.) Adoptive Immunotherapy X.E.) Administration of Vaccines for Therapeutic or Prophylactic Purposes XL.) Diagnostic and Prognostic Embodiments of 109P1 D4. XI.) Inhibition of 109P1D4 Protein Function XIIA.) Inhibition of 109P1D4 With Intracellular Antibodies XII.B.) Inhibition of 109P1D4 with Recombinant Proteins XII.C.) Inhibition of 109PI D4 Transcription or Translation XII.D.) General Considerations for Therapeutic Strategies XIII.) Identification, Characterization and Use of Modulators of 109PiD4 XIV.) KITSIArticles of Manufacture WO 2004/098515 PCT/US2004/013568 11 I.) Definitions: Unless otherwise defined, all terms of art, notations and other scientific terms or terminology used herein are intended to have the meanings commonly understood by those of skill in the art to which this invention pertains. In some cases, terms with commonly understood meanings are defined herein for clarity and/or for ready reference, and the inclusion of such definitions herein should not necessarily be construed to represent a substantial difference over what is generally understood in the art. Many of the techniques and procedures described or referenced herein are well understood and commonly employed using conventional methodology by those skilled in the art, such as, for example, the widely utilized molecular cloning methodologies described in Sambrook et al., Molecular Cloning: A Laboratory Manual 2nd. edition (1989) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. As appropriate, procedures involving the use of commercially available kits and reagents are generally carried out in accordance with manufacturer defined protocols and/or parameters unless otherwise noted. The terms "advanced prostate cancer", "locally advanced prostate cancer", "advanced disease" and "locally advanced disease" mean prostate cancers that have extended through the prostate capsule, and are meant to include stage C disease under the American Urological Association (AUA) system, stage CI - C2 disease under the Whitmore-Jewett system, and stage T3 - T4 and N+ disease under the TNM (tumor, node, metastasis) system. In general, surgery is not recommended for patients with locally advanced disease, and these patients have substantially less favorable outcomes compared to patients having clinically localized (organ-confined) prostate cancer. Locally advanced disease is clinically identified by palpable evidence of induration beyond the lateral border of the prostate, or asymmetry or induration above the prostate base. Locally advanced prostate cancer is presently diagnosed pathologically following radical prostatectomy if the tumor invades or penetrates the prostatic capsule, extends into the surgical margin, or invades the seminal vesicles. "Altering the native glycosylation pattern" is intended for purposes herein to mean deleting one or more carbohydrate moieties found in native sequence 109P1 D4 (either by removing the underlying glycosylation site or by deleting the glycosylation by chemical and/or enzymatic means), and/or adding one or more glycosylation sites that are not present in the native sequence 109P1D4. In addition, the phrase includes qualitative changes in the glycosylation of the native proteins, involving a change in the nature and proportions of the various carbohydrate moieties present. The term "analog" refers to a molecule which is structurally similar or shares similar or corresponding attributes with another molecule (e.g. a 109P1D4-related protein). For example, an analog of a 109P1D4 protein can be specifically bound by an antibody orT cell that specifically binds to 109PI D4. The term "antibody" is used in the broadest sense. Therefore, an "antibody" can be naturally occurring or man-made such as monoclonal antibodies produced by conventional hybridoma technology. Ant-109P1D4 antibodies comprise monoclonal and polyclonal antibodies as well as fragments containing the antigen-binding domain and/or one or more complementarity determining regions of these antibodies. An "antibody fragment" is defined as at least a portion of the variable region of the immunoglobulin molecule that binds to its target, i.e., the antigen-binding region. In one embodiment it specifically covers single anti-109P1D4 antibodies and clones thereof (including agonist, antagonist and neutralizing antibodies) and anti-I 09P1 D4 antibody compositions with polyepitopic specificity. The term "codon optimized sequences" refers to nucleotide sequences that have been optimized for a particular host species by replacing any codons having a usage frequency of less than about 20%, Nucleotide sequences that have been optimized for expression in a given host species by elimination of spurious polyadenylation sequences, elimination of exonlintron splicing signals, elimination of transposon-like repeats and/or optimization of GC content in addition to codon WO 2004/098515 PCT/US2004/013568 12 optimization are referred to herein as an "expression enhanced sequences." A "combinatorial library" is a collection of diverse chemical compounds generated by either chemical synthesis or biological synthesis by combining a number of chemical "building blocks" such as reagents. For example, a linear combinatorial chemical library, such as a polypeptide (e.g., mutein) library, is formed by combining a set of chemical building blocks called amino acids in every possible way for a given compound length (i.e., the number of amino acids in a polypeptide compound). Numerous chemical compounds are synthesized through such combinatorial mixing of chemical building blocks (Gallop et al., J. Med. Chem. 37(9): 1233-1251 (1994)). Preparation and screening of combinatorial libraries is well known to those of skill in the art. Such combinatorial chemical libraries include, but are not limited to, peptide libraries (see, e.g., U.S. Patent No. 5,010,175, Furka, Pept. Prot. Res. 37:487-493 (1991), Houghton et al., Nature, 354:84-88 (1991)), peptoids (PCT Publication No WO 91/19735), encoded peptides (PCT Publication WO 93/20242), random bio- oligomers (PCT Publication WO 92/00091), benzodiazepines (U.S. Pat. No. 5,288,514), diversomers such as hydantoins, benzodiazepines and dipeptides (Hobbs et al., Proc. Nat. Acad. Sci. USA 90:6909-6913 (1993)), vinylogous polypeptides (Hagihara et al., J. Amer. Chem. Soc. 114:6568 (1992)), nonpeptidal peptidomimetics with a Beta-D-Glucose scaffolding (Hirschmann et al., J. Amer. Chem. Soc. 114:9217-9218 (1992)), analogous organic syntheses of small compound libraries (Chen et al., J. Amer. Chem. Soc. 116:2661 (1994)), oligocarbarnates (Cho, et al., Science 261:1303 (1993)), and/or peptidyl phosphonates (Campbell et al., J. Org. Chem. 59:658 (1994)). See, generally, Gordon et al., J. Med. Chem. 37:1385 (1994), nucleic acid libraries (see, e.g., Stratagene, Corp.), peptide nucleic acid libraries (see, e.g., U.S. Patent 5,539,083), antibody libraries (see, e.g., Vaughn et al., Nature Biotechnology 14(3): 309-314 (1996), and PCT/US96/10287), carbohydrate libraries (see, e.g., Liang et al., Science 274:1520-1522 (1996), and U.S. Patent No. 5,593,853), and small organic molecule libraries (see, e.g., benzodiazepines, Baum, C&EN, Jan 18, page 33 (1993); isoprenoids, U.S. Patent No. 5,569,588; thiazolidinones and metathiazanones, U.S. Patent No. 5,549,974; pyrrolidines, U.S. Patent Nos. 5,525,735 and 5,519,134; morpholino compounds, U.S. Patent No. 5,506, 337; benzodiazepines, U.S. Patent No. 5,288,514; and the like). Devices for the preparation of combinatorial libraries are commercially available (see, e.g., 357 NIPS, 390 NIPS, Advanced Chem Tech, Louisville KY; Symphony, Rainin, Woburn, MA; 433A, Applied Biosystems, Foster City, CA; 9050, Plus, Millipore, Bedford, NIA). A number of well-known robotic systems have also been developed for solution phase chemistries. These systems include automated workstations such as the automated synthesis apparatus developed by Takeda Chemical Industries, LTD. (Osaka, Japan) and many robotic systems utilizing robotic arms (Zymate H, Zymark Corporation, Hopkinton, Mass.; Orca, Hewlett-Packard, Palo Alto, Calif.), which mimic the manual synthetic operations performed by a chemist. Any of the above devices are suitable for use with the present invention. The nature and implementation of modifications to these devices (if any) so that they can operate as discussed herein will be apparent to persons skilled in the relevant art. In addition, numerous combinatorial libraries are themselves commercially available (see, e.g., ComGenex, Princeton, NJ; Asinex, Moscow, RU; Tripos, Inc., St. Louis, MO; ChemStar, Ltd, Moscow, RU; 3D Pharmaceuticals, Exton, PA; Martek Biosciences, Columbia, MD; etc.). The term "cytotoxic agent" refers to a substance that inhibits or prevents the expression activity of cells, function of cells and/or causes destruction of cells. The term is intended to include radioactive isotopes chemotherapeutic agents, and toxins such as small molecule toxins or enzymatically active toxins of bacterial, fungal, plant or animal origin, including fragments and/or variants thereof. Examples of cytotoxic agents include, but are not limited to auristatins, auromycins, maytansinoids, yttrium, bismuth, ricin, ricin A-chain, combrestatin, duocarmycins, dolostatins, doxorubicin, daunorubicin, taxol, cisplatin, cc1065, ethidium bromide, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicine, dihydroxy anthracin dione, actinomycin, diphtheria toxin, Pseudomonas exotoxin (PE) A, PE40, abrin, abrin A chain, modeccin A chain, WO 2004/098515 PCT/US2004/013568 13 alpha-sarcin, gelonin, mitogellin, retstrictocin, phenomycin, enomycin, curicin, crotin, calicheamicin, Sapaonaria officinalis inhibitor, and glucocorticoid and other chemotherapeutic agents, as well as radioisotopes such as At211, 1131, 1125, Y90, Rei6, ReiB, Sm 1 83 , Bi212or 2 1 3 , p32 and radioactive isotopes of Lu including Lu 1 '. Antibodies may also be conjugated to an anti cancer pro-drug activating enzyme capable of converting the pro-drug to its active form. The "gene product" is sometimes referred to herein as a protein or mRNA. For example, a "gene product of the invention" is sometimes referred to herein as a "cancer amino acid sequence", "cancer protein", "protein of a cancer listed in Table I", a "cancer mRNA", "mRNA of a cancer listed in Table I", etc. In one embodiment, the cancer protein is encoded by a nucleic acid of Figure 2. The cancer protein can be a fragment, or alternatively, be the full-length protein to the fragment encoded by the nucleic acids of Figure 2. In one embodiment, a cancer amino acid sequence is used to determine sequence identity or similarity. In another embodiment, the sequences are naturally occurring allelic variants of a protein encoded by a nucleic acid of Figure 2. In another embodiment, the sequences are sequence variants as further described herein. "High throughput screening" assays for the presence, absence, quantification, or other properties of particular nucleic acids or protein products are well known to those of skill in the art. Similarly, binding assays and reporter gene assays are similarly well known. Thus, e.g., U.S. Patent No. 5,559,410 discloses high throughput screening methods for proteins; U.S. Patent No. 5,585,639 discloses high throughput screening methods for nucleic acid binding (i.e., in arrays); while U.S. Patent Nos. 5,576,220 and 5,541,061 disclose high throughput methods of screening for ligand/antibody binding. In addition, high throughput screening systems are commercially available (see, e.g., Amersham Biosciences, Piscataway, NJ; Zymark Corp., Hopkinton, MA; Air Technical Industries, Mentor, OH; Beckman Instruments, Inc. Fullerton, CA; Precision Systems, Inc., Natick, MA; etc.). These systems typically automate entire procedures, including all sample and reagent pipetting, liquid dispensing, timed incubations, and final readings of the microplate in detector(s) appropriate for the assay. These configurable systems provide high throughput and rapid start up as well as a high degree of flexibility and customization. The manufacturers of such systems provide detailed protocols for various high throughput systems. Thus, e.g., Zymark Corp. provides technical bulletins describing screening systems for detecting the modulation of gene transcription, ligand binding, and the like. The term "homolog" refers to a molecule which exhibits homology to another molecule, by for example, having sequences of chemical residues that are the same or similar at corresponding positions. "Human Leukocyte Antigen" or "HLA" is a human class I or class II Major Histocompatibility Complex (MHC) protein (see, e.g., Stites, et al., IMMUNOLOGY, 8TH ED., Lange Publishing, Los Altos, CA (1994). The terms "hybridize", "hybridizing", "hybridizes" and the like, used in the context of polynucleotides, are meant to refer to conventional hybridization conditions, preferably such as hybridization in 50% formamide/6XSSC/0.1% SDS/100 [ig/ml ssDNA, in which temperatures for hybridization are above 37 degrees C and temperatures for washing in 0.1XSSC/0.1 % SDS are above 55 degrees C. The phrases "isolated" or "biologically pure" refer to material which is substantially or essentially free from components which normally accompany the material as it is found in its native state. Thus, isolated peptides in accordance with the invention preferably do not contain materials normally associated with the peptides in their in situ environment. For example, a polynucleotide is said to be "isolated" when it is substantially separated from contaminant polynucleotides that correspond or are complementary to genes other than the 109P1 D4 genes or that encode polypeptides other than 109P1 D4 gene product or fragments thereof. A skilled artisan can readily employ nucleic acid isolation procedures to obtain an isolated 109P1 D4 polynucleotide. A protein is said to be "isolated," for example, when physical, mechanical or chemical methods are employed to remove the 109P1D4 proteins from cellular constituents that are normally associated with the protein. A skilled artisan can readily WO 2004/098515 PCT/US2004/013568 14 employ standard purification methods to obtain an isolated 109P1 D4 protein. Alternatively, an isolated protein can be prepared by chemical means. The term "mammal" refers to any organism classified as a mammal, including mice, rats, rabbits, dogs, cats, cows, horses and humans. In one embodiment of the invention, the mammal is a mouse. In another embodiment of the invention, the mammal is a human. The terms "metastatic prostate cancer" and "metastatic disease" mean prostate cancers that have spread to regional lymph nodes or to distant sites, and are meant to include stage D disease under the AUA system and stage TxNxM+ under the TNM system. As is the case with locally advanced prostate cancer, surgery is generally not indicated for patients with metastatic disease, and hormonal (androgen ablation) therapy is a preferred treatment modality. Patients with metastatic prostate cancer eventually develop an androgen-refractory state within 12 to 18 months of treatment initiation. Approximately half of these androgen-refractory patients die within 6 months after developing that status. The most common site for prostate cancer metastasis is bone. Prostate cancer bone metastases are often osteoblastic rather than osteolytic (i.e., resulting in net bone formation). Bone metastases are found most frequently in the spine, followed by the femur, pelvis, rib cage, skull and humerus. Other common sites for metastasis include lymph nodes, lung, liver and brain. Metastatic prostate cancer is typically diagnosed by open or laparoscopic pelvic lymphadenectomy, whole body radionuclide scans, skeletal radiography, and/or bone lesion biopsy. The term "modulator" or "test compound" or "drug candidate" or grammatical equivalents as used herein describe any molecule, e.g., protein, oligopeptide, small organic molecule, polysaccharide, polynucleotide, etc., to be tested for the capacity to directly or indirectly alter the cancer phenotype or the expression of a cancer sequence, e.g., a nucleic acid or protein sequences, or effects of cancer sequences (e.g., signaling, gene expression, protein interaction, etc.) In one aspect, a modulator will neutralize the effect of a cancer protein of the invention. By "neutralize" is meant that an activity of a protein is inhibited or blocked, along with the consequent effect on the cell. In another aspect, a modulator will neutralize the effect of a gene, and its corresponding protein, of the invention by normalizing levels of said protein. In preferred embodiments, modulators alter expression profiles, or expression profile nucleic acids or proteins provided herein, or downstream effector pathways. In one embodiment, the modulator suppresses a cancer phenotype, e.g. to a normal tissue fingerprint. In another embodiment, a modulator induced a cancer phenotype. Generally, a plurality of assay mixtures is run in parallel with different agent concentrations to obtain a differential response to the various concentrations. Typically, one of these concentrations serves as a negative control, i.e., at zero concentration or below the level of detection. Modulators, drug candidates or test compounds encompass numerous chemical classes, though typically they are organic molecules, preferably small organic compounds having a molecular weight of more than 100 and less than about 2,500 Daltons. Preferred small molecules are less than 2000, or less than 1500 or less than 1000 or less than 500 D. Candidate agents comprise functional groups necessary for structural interaction with proteins, particularly hydrogen bonding, and typically include at least an amine, carbonyl, hydroxyl or carboxyl group, preferably at least two of the functional chemical groups. The candidate agents often comprise cyclical carbon or heterocyclic structures and/or aromatic or polyaromatic structures substituted with one or more of the above functional groups. Modulators also comprise biomolecules such as peptides, saccharides, fatty acids, steroids, purines, pyrimidines, derivatives, structural analogs or combinations thereof. Particularly preferred are peptides. One class of modulators are peptides, for example of from about five to about 35 amino acids, with from about five to about 20 amino acids being preferred, and from about 7 to about 15 being particularly preferred. Preferably, the cancer modulatory protein is soluble, includes a non-transmembrane region, and/or, has an N terminal Cys to aid in solubility. In one embodiment, the C-terminus of the fragment is kept as a free acid and the N-terminus is a free amine to aid in coupling, i.e., to cysteine. In one embodiment, a cancer protein of the invention is conjugated to an WO 2004/098515 PCT/US2004/013568 immunogenic agent as discussed herein. In one embodiment, the cancer protein is conjugated to BSA. The peptides of the invention, e.g., of preferred lengths, can be linked to each other or to other amino acids to create a longer peptide/protein. The modulatory peptides can be digests of naturally occurring proteins as is outlined above, random peptides, or "biased" random peptides. In a preferred embodiment, peptide/protein-based modulators are antibodies, and fragments thereof, as defined herein. Modulators of cancer can also be nucleic acids. Nucleic acid modulating agents can be naturally occurring nucleic acids, random nucleic acids, or "biased" random nucleic acids. For example, digests of prokaryotic or eukaryotic genomes can be used in an approach analogous to that outlined above for proteins. The term "monoclonal antibody" refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the antibodies comprising the population are identical except for possible naturally occurring mutations that are present in minor amounts. A "motif', as in biological motif of a 109PID4-related protein, refers to any pattern of amino acids forming part of the primary sequence of a protein, that is associated with a particular function (e.g. protein-protein interaction, protein-DNA interaction, etc) or modification (e.g. that is phosphorylated, glycosylated or amidated), or localization (e.g. secretory sequence, nuclear localization sequence, etc.) or a sequence that is correlated with being immunogenic, either humorally or cellularly. A motif can be either contiguous or capable of being aligned to certain positions that are generally correlated with a certain function or property. In the context of HLA motifs, "motif' refers to the pattern of residues in a peptide of defined length, usually a peptide of from about 8 to about 13 amino acids for a class I HLA motif and from about 6 to about 25 amino acids for a class II HLA motif, which is recognized by a particular HLA molecule. Peptide motifs for HLA binding are typically different for each protein encoded by each human HLA allele and differ in the pattern of the primary and secondary anchor residues. A "pharmaceutical excipient" comprises a material such as an adjuvant, a carrier, pH-adjusting and buffering agents, tonicity adjusting agents, wetting agents, preservative, and the like. "Pharmaceutically acceptable" refers to a non-toxic, inert, and/or composition that is physiologically compatible with humans or other mammals. The term "polynucleotide" means a polymeric form of nucleotides of at least 10 bases or base pairs in length, either ribonucleotides or deoxynucleotides or a modified form of either type of nucleotide, and is meant to include single and double stranded forms of DNA and/or RNA. In the art, this term if often used interchangeably with "oligonucleotide". A polynucleotide can comprise a nucleotide sequence disclosed herein wherein thymidine (T), as shown for example in Figure 2, can also be uracil (U); this definition pertains to the differences between the chemical structures of DNA and RNA, in particular the observation that one of the four major bases in RNA is uracil (U) instead of thymidine (T). The term "polypeptide" means a polymer of at least about 4, 5, 6, 7, or 8 amino acids. Throughout the specification, standard three letter or single letter designations for amino acids are used. In the art, this term is often used interchangeably with "peptide" or "protein". An HLA "primary anchor residue" is an amino acid at a specific position along a peptide sequence which is understood to provide a contact point between the immunogenic peptide and the HLA molecule. One to three, usually two, primary anchor residues within a peptide of defined length generally defines a "motif' for an immunogenic peptide. These residues are understood to fit in close contact with peptide binding groove of an HLA molecule, with their side chains buried in specific pockets of the binding groove. In one embodiment, for example, the primary anchor residues for an HLA class I molecule are located at position 2 (from the amino terminal position) and at the carboxyl terminal position of a 8, 9, 10, 11, or 12 residue peptide epitope in accordance with the invention. Alternatively, in another embodiment, the primary anchor WO 2004/098515 PCT/US2004/013568 16 residues of a peptide binds an HLA class il molecule are spaced relative to each other, rather than to the termini of a peptide, where the peptide is generally of at least 9 amino acids in length. The primary anchor positions for each motif and supermotif are set forth in Table IV. For example, analog peptides can be created by altering the presence or absence of particular residues in the primary and/or secondary anchor positions shown in Table IV. Such analogs are used to modulate the binding affinity and/or population coverage of a peptide comprising a particular HLA motif or supermotif. "Radioisotopes" include, but are not limited to the following (non-limiting exemplary uses are also set forth): Examples of Medical Isotopes: Isotope Description of use Actinium-225 See Thorium-229 (Th-229) (AC-225) Actinium-227' Parent of Radium-223 (Ra-223) which is an alpha emitter used to treat metastases in the skeleton (AC-227) resulting from cancer (i.e., breast and prostate cancers), and cancer radioimmunotherapy Bismuth-212 See Thorium-228 (Th-228) (Bi-21 2) Bismuth-213 See Thorium-229 (Th-229) (Bi-21 3) Cadmium-109 Cancer detection (Cd-i 09) Cobalt-60 Radiation source for radiotherapy of cancer, for food irradiators, and for sterilization of medical (Co-60) supplies Copper-64 A positron emitter used for cancer therapy and SPECT imaging (Cu-64) Copper-67 Betalgamma emitter used in cancer radioimmunotherapy and diagnostic studies (i.e., breast and (Cu-67) colon cancers, and lymphoma) Dysprosium-166 Cancer radioimmunotherapy (Dy-i 66) Erbium- 169 Rheumatoid arthritis treatment, particularly for the small joints associated with fingers and toes (Er-1 69) Europium-152 Radiation source for food irradiation and for sterilization of medical supplies (Eu-i 52) Europium-i 54 Radiation source for food irradiation and for sterilization of medical supplies (Eu-l 54) Gadolinium-153 Osteoporosis detection and nuclear medical quality assurance devices (Gd-i 53) Gold-198 Implant and intracavity therapy of ovarian, prostate, and brain cancers (Au-I 98) Holmium-166 Multiple myeloma treatment in targeted skeletal therapy, cancer radioimmunotherapy, bone (Ho-166) marrow ablation, and rheumatoid arthritis treatment Osteoporosis detection, diagnostic imaging, tracer drugs, brain cancer treatment, radiolabeling, Iodine-125 tumor imaging, mapping of receptors in the brain, interstitial radiation therapy, brachytherapy for (1-125) treatment of prostate cancer, determination of glomerular filtration rate (GFR), determination of plasma volume, detection of deep vein thrombosis of the legs Iodine-i3i Thyroid function evaluation, thyroid disease detection, treatment of thyroid cancer as well as other li-131) non-malignant thyroid diseases (i.e., Graves disease, goiters, and hyperthyroidism), treatment of (1-1 leukemia, lymphoma, and other forms of cancer (e.g., breast cancer) using radioimmunotherapy Iridium-192 Brachytherapy, brain and spinal cord tumor treatment, treatment of blocked arteries (i.e., (Ir-192) arteriosclerosis and restenosis), and implants for breast and prostate tumors Lutetium-177 Cancer radioimmunotherapy and treatment of blocked arteries (i.e., arteriosclerosis and (Lu-1 77) restenosis) Parent of Technetium-99m (Tc-99m} which is used for imaging the brain, liver, lungs, heart, and Molybdenum-99 other organs. Currently, Tc-99m is the most widely used radioisotope used for diagnostic imaging (Mo-99) of various cancers and diseases involving the brain, heart, liver, lungs; also used in detection of deep vein thrombosis of the legs Osmium-194 Cancer radioimmunotherapy (Os-i94) WO 2004/098515 PCT/US2004/013568 17 Palladium- 103 Prostate cancer treatment (Pd-i 03) Platinum-195m Studies on biodistribution and metabolism of cisplatin, a chemotherapeutic drug (Pt-195m) Polycythemia rubra vera (blood cell disease) and leukemia treatment, bone cancer Phosphorus-32 diagnosis/treatment; colon, pancreatic, and liver cancer treatment; radiolabeling nucleic acids for (P-32) in vitro research, diagnosis of superficial tumors, treatment of blocked arteries (i.e., arteriosclerosis and restenosis), and intracavity therapy Phosphorus-33 Leukemia treatment, bone disease diagnosis/treatment, radiolabeling, and treatment of blocked (P-33) arteries (i.e., arteriosclerosis and restenosis) Radium-223 See Actinium-227 (Ac-227) (Ra-223) Rhenium-1 86 Bone cancer pain relief, rheumatoid arthritis treatment, and diagnosis and treatment of lymphoma (Re-186) and bone, breast, colon, and liver cancers using radioimmunotherapy Rhenium-188 Cancer diagnosis and treatment using radioimmunotherapy, bone cancer pain relief, treatment of (Re-188) rheumatoid arthritis, and treatment of prostate cancer Rhodium- 105 Cancer radioimmunotherapy (Rh-i O5 Samarium-145 Ocular cancer treatment (Sm-145) Samarium-47 Cancer radioimmunotherapy and bone cancer pain relief (Sm-153) Scandium-47 Cancer radioimmunotherapy and bone cancer pain relief (Sc-47) Radiotracer used in brain studies, imaging of adrenal cortex by gamma-scintigraphy, lateral Selenium-75 locations of steroid secreting tumors, pancreatic scanning, detection of hyperactive parathyroid (Se-75) glands, measure rate of bile acid loss from the endogenous pool Strontium-85- Bone cancer detection and brain scans (Sr-85), Strontium-89 Bone cancer pain relief, multiple myeloma treatment, and osteoblastic therapy (Sr-89) Technetium-99m See Molybdenum-99 (Mo-99) (Tc-ggm) Thorium-228 Parent of Bismuth-212 (Bi-212) which is an alpha emitter used in cancer radioimmunotherapy (Th-228) Thorium-229 Parent of Actinium-225 (Ac-225) and grandparent of Bismuth-213 (Bi-213) which are alpha (Th-229) emitters used in cancer radioimmunotherapy Thulium-170 Gamma source for blood irradiators, energy source for implanted medical devices ( Tm-170) (Sn-i 7m Cancer immunotherapy and bone cancer pain relief Parent for Rhenium-1 88 (Re-188) which is used for cancer diagnostics/treatment, bone cancer Tungsten-1 88 pain relief, rheumatoid arthritis treatment, and treatment of blocked arteries (i.e., arteriosclerosis (W-188) and restenosis) Xenon-127 Neuroimaging of brain disorders, high resolution SPECT studies, pulmonary function tests, and (Xe-127) cerebral blood flow studies Ytterbium-175 Cancer radioimmunotherapy (Yb-i 75) Yttrium-90 Microseeds obtained from irradiating Yttrium-89 (Y-89) for liver cancer treatment (Y-90) Yttrium- i A gamma-emitting label for Yttrium-90 (Y-90) which is used for cancer radioimmunotherapy (i.e., Ym-91 lymphoma, breast, colon, kidney, lung, ovarian, prostate, pancreatic, and inoperable liver (Y-91) cancers) WO 2004/098515 PCT/US2004/013568 18 By "randomized" or grammatical equivalents as herein applied to nucleic acids and proteins is meant that each nucleic acid and peptide consists of essentially random nucleotides and amino acids, respectively. These random peptides (or nucleic acids, discussed herein) can incorporate any nucleotide or amino acid at any position. The synthetic process can be designed to generate randomized proteins or nucleic acids, to allow the formation of all or most of the possible combinations over the length of the sequence, thus forming a library of randomized candidate bioactive proteinaceous agents. In one embodiment, a library is "fully randomized," with no sequence preferences or constants at any position. In another embodiment, the library is a "biased random" library. That is, some positions within the sequence either are held constant, or are selected from a limited number of possibilities. For example, the nucleotides or amino acid residues are randomized within a defined class, e.g., of hydrophobic amino acids, hydrophilic residues, sterically biased (either small or large) residues, towards the creation of nucleic acid binding domains, the creation of cysteines, for cross-linking, prolines for SH-3 domains, serines, threonines, tyrosines or histidines for phosphorylation sites, etc., or to purines, etc. A "recombinant' DNA or RNA molecule is a DNA or RNA molecule that has been subjected to molecular manipulation in vitro. Non-limiting examples of small molecules include compounds that bind or interact with 109P1 D4, ligands including hormones, neuropeptides, chemokines, odorants, phospholipids, and functional equivalents thereof that bind and preferably inhibit 109P1 D4 protein function. Such non-limiting small molecules preferably have a molecular weight of less than about 10 kDa, more preferably below about 9, about 8, about 7, about 6, about 5 or about 4 kDa. In certain embodiments, small molecules physically associate with, or bind, 109P1D4 protein; are not found in naturally occurring metabolic pathways; and/or are more soluble in aqueous than non-aqueous solutions "Stringency" of hybridization reactions is readily determinable by one of ordinary skill in the art, and generally is an empirical calculation dependent upon probe length, washing temperature, and salt concentration. In general, longer probes require higher temperatures for proper annealing, while shorter probes need lower temperatures. Hybridization generally depends on the ability of denatured nucleic acid sequences to reanneal when complementary strands are present in an environment below their melting temperature. The higher the degree of desired homology between the probe and hybridizable sequence, the higher the relative temperature that can be used. As a result, it follows that higher relative temperatures would tend to make the reaction conditions more stringent, while lower temperatures less so. For additional details and explanation of stringency of hybridization reactions, see Ausubel et al., Current Protocols in Molecular Biology, Wiley Interscience Publishers, (1995). "Stringent conditions" or "high stringency conditions", as defined herein, are identified by, but not limited to, those that: (1) employ low ionic strength and high temperature for washing, for example 0.015 M sodium chloride/0.0015 M sodium citrate/0.1 % sodium dodecyl sulfate at 50CC; (2) employ during hybridization a denaturing agent, such as formamide, for example, 50% (v/v) formamide with 0.1% bovine serum albumin/0.1 % Ficoll/0.1 % polyvinylpyrrolidone/50 mM sodium phosphate buffer at pH 6.5 with 750 mM sodium chloride, 75 mM sodium citrate at 42 OC; or (3) employ 50% formamide, 5 x SSC (0.75 M NaCl, 0.075 M sodium citrate), 50 mM sodium phosphate (pH 6.8), 0.1% sodium pyrophosphate, 5 x Denhardt's solution, sonicated salmon sperm DNA (50 pig/ml), 0.1% SDS, and 10% dextran sulfate at 42 oC, with washes at 420C in 0.2 x SSC (sodium chloride/sodium. citrate) and 50% formamide at 55 oC, followed by a high-stringency wash consisting of 0.1 x SSC containing EDTA at 55 0C. "Moderately stringent conditions" are described by, but not limited to, those in Sambrook et aL., Molecular Cloning: A Laboratory Manual, New York: Cold Spring Harbor Press, 1989, and include WO 2004/098515 PCT/US2004/013568 19 the use of washing solution and hybridization conditions (e.g., temperature, ionic strength and %SDS) less stringent than those described above. An example of moderately stringent conditions is overnight incubation at 37oC in a solution comprising: 20% formamide, 5 x SSC (150 mM NaCl, 15 mM trisodium citrate), 50 mM sodium phosphate (pH 7.6), 5 x Denhardts solution, 10% dextran sulfate, and 20 mg/mL denatured sheared salmon sperm DNA, followed by washing the filters in 1 x SSC at about 37-50CC. The skilled artisan will recognize how to adjust the temperature, ionic strength, etc. as necessary to accommodate factors such as probe length and the like. An HLA "supermotif is a peptide binding specificity shared by HLA molecules encoded by two or more HLA alleges. Overall phenotypic frequencies of HLA-supertypes in different ethnic populations are set forth in Table IV (F). The non limiting constituents of various supetypes are as follows: A2: A*0201, A*0202, A*0203, A*0204, A* 0205, A*0206, A*6802, A*6901, A*0207 A3: A3, Al1, A31, A*3301, A*6801, A*0301, A*1101, A*3101 B7: B7, B*3501-03, B*51, B*5301, B*5401, B*5501, B*5502, B*5601, 8*6701, B*7801, B*0702, B*5101, B*5602 B44: B*3701, B*4402, B*4403, B*60 (B*4001), B61 (B*4006) Al: A*01 02, A*2604, A*3601, A*4301, A*8001 A24 A*24, A*30, A*2403, A*2404, A*3002, A*3003 B27: B*1401-02, B*1503, B*1509, B*1510, B*1518, B*3801-02, B*3901, B*3902, B*3903-04, B*4801-02, B*7301, B*2701-08 B58. B*1516, B*1517, B*5701, B*5702, B58 B62; B*4601, B52, 8*1501 (B62), B*1502 (B75), B*1513 (877) Calculated population coverage afforded by different HLA-supertype combinations are set forth in Table IV (G). As used herein "to treat" or "therapeutic" and grammatically related terms, refer to any improvement of any consequence of disease, such as prolonged survival, less morbidity, and/or a lessening of side effects which are the byproducts of an alternative therapeutic modality; full eradication of disease is not required. A "transgenic animal" (e.g., a mouse or rat) is an animal having cells that contain a transgene, which transgene was introduced into the animal or an ancestor of the animal at a prenatal, e.g., an embryonic stage. A "transgene" is a DNA that is integrated into the genome of a cell from which a transgenic animal develops. As used herein, an HLA or cellular immune response "vaccine" is a composition that contains or encodes one or more peptides of the invention. There are numerous embodiments of such vaccines, such as a cocktail of one or more individual peptides; one or more peptides of the invention comprised by a polyepitopic peptide; or nucleic acids that encode such individual peptides or polypeptides, e.g., a minigene that encodes a polyepitopic peptide. The "one or more peptides" can include any whole unit integer from 1-150 or more, e.g., at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, or 150 or more peptides of the invention. The peptides or polypeptides can optionally be modified, such as by lipidation, addition of targeting or other sequences. HLA class I peptides of the invention can be admixed with, or linked to, HLA class Il peptides, to facilitate activation of both cytotoxic T lymphocytes and helper T lymphocytes. HLA vaccines can also comprise peptide-pulsed antigen presenting cells, e.g., dendritic cells. The term "variant' refers to a molecule that exhibits a variation from a described type or norm, such as a protein that has one or more different amino acid residues in the corresponding position(s) of a specifically described protein (e.g. the 109P1D4 protein shown in Figure 2 or Figure 3. An analog is an example of a variant protein. Splice isoforms and single nucleotides polymorphisms (SNPs) are further examples of variants.

WO 2004/098515 PCT/US2004/013568 20 The "109P104-related proteins" of the invention include those specifically identified herein, as well as allelic variants, conservative substitution variants, analogs and homologs that can be isolated/generated and characterized without undue experimentation following the methods outlined herein or readily available in the art. Fusion proteins that combine parts of different 109P1 D4 proteins or fragments thereof, as well as fusion proteins of a 109P1 D4 protein and a heterologous polypeptide are also included. Such 109P1 D4 proteins are collectively referred to as the 109P1 D4-related proteins, the proteins of the invention, or 109P1D4. The term "1 09P1 D4-related protein" refers to a polypeptide fragment or a 109P1D4 protein sequence of 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or more than 25 amino acids; or, at least 30, 35, 40, 45, 50, 55, 60, 65, 70, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 575, or 576 or more amino acids. 11.) 109P1D4 Polynucleotides One aspect of the invention provides polynucleotides corresponding or complementary to all or part of a 109P1 D4 gene, mRNA, and/or coding sequence, preferably in isolated form, including polynucleotides encoding a 109P1 D4-related protein and fragments thereof, DNA, RNA, DNA/RNA hybrid, and related molecules, polynucleotides or oligonucleotides complementary to a 109P1D4 gene or mRNA sequence or a part thereof, and polynucleotides or oligonucleotides that hybridize to a 109P1D4 gene, mRNA, or to a 109P1D4 encoding polynucleotide (collectively, "109P1D4 polynucleotides"). In all instances when referred to in this section, T can also be U in Figure 2. Embodiments of a 109P1D4 polynucleotide include: a 109P1D4 polynucleotide having the sequence shown in Figure 2, the nucleotide sequence of 109P1D4 as shown in Figure 2 wherein T is U; at least 10 contiguous nucleotides of a polynucleotide having the sequence as shown in Figure 2; or, at least 10 contiguous nucleotides of a polynucleotide having the sequence as shown in Figure 2 where T is U. For example, embodiments of 109P1D4 nucleotides comprise, without limitation: (I) a polynucleotide comprising, consisting essentially of, or consisting of a sequence as shown in Figure 2, wherein T can also be U; (11) a polynucleotide comprising, consisting essentially of, or consisting of the sequence as shown in Figure 2A, from nucleotide residue number 846 through nucleotide residue number 3911, including the stop codon, wherein T can also be U; (1ll) a polynucleotide comprising, consisting essentially of, or consisting of the sequence as shown in Figure 2B, from nucleotide residue number 503 through nucleotide residue number 3667, including the stop codon, wherein T can also be U; (IV) a polynucleotide comprising, consisting essentially of, or consisting of the sequence as shown in Figure 2C, from nucleotide residue number 846 through nucleotide residue number 4889, including the a stop codon, wherein T can also be U; (V) a polynucleotide comprising, consisting essentially of, or consisting of the sequence as shown in Figure 2D, from nucleotide residue number 846 through nucleotide residue number 4859, including the stop codon, wherein T can also be U; (VI) a polynucleotide comprising, consisting essentially of, or consisting of the sequence as shown in Figure 2E, from nucleotide residue number 846 through nucleotide residue number 4778, including the stop codon, wherein T can also be U; WO 2004/098515 PCT/US2004/013568 21 (VII) a polynucleotide comprising, consisting essentially of, or consisting of the sequence as shown in Figure 2F, from nucleotide residue number 614 through nucleotide residue number 3727, including the stop codon, wherein T can also be U; (VIII) a polynucleotide comprising, consisting essentially of, or consisting of the sequence as shown in Figure 2G, from nucleotide residue number 735 through nucleotide residue number 3881, including the stop codon, wherein T can also be U; (IX) a polynucleotide comprising, consisting essentially of, or consisting of the sequence as shown in Figure 2H, from nucleotide residue number 735 through nucleotide residue number 4757, including the stop codon, wherein T can also be U; (X) a polynucleotide comprising, consisting essentially of, or consisting of the sequence as shown in Figure 21, from nucleotide residue number 514 through nucleotide residue number 3627, including the stop codon, wherein T can also be U; (XI) a polynucleotide that encodes a 109P1 D4-related protein that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% homologous to an entire amino acid sequence shown in Figure 2A-l; (XII) a polynucleotide that encodes a 109P1 D4-related protein that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% identical to an entire amino acid sequence shown in Figure 2A-1; (XIII) a polynucleotide that encodes at least one peptide set forth in Tables VIII-XXI and XXII-XLIX; (XIV) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figures 3A in any whole number increment up to 1021 that includes at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Hydrophilicity profile of Figure 5; (XV) a polynuceotide that encodes a peptide region of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3A in any whole number increment up to 1021 that includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value less than 0.5 in the Hydropathicity profile of Figure 6; (XVI) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3A in any whole number increment up to 1021 that includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Percent Accessible Residues profile of Figure 7; (XVII) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3A in any whole number increment up to 1021 that includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Average Flexibility profile of Figure 8; (XVII) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, 17, WO 2004/098515 PCT/US2004/013568 22 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3A in any whole number increment up to 1021 that includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Beta-turn profile of Figure 9; (XIX) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3B, 3C, and/or 3D in any whole number increment up to 1054, 1347, and/or 1337 respectively that includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13,14,15,16,17,18,19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Hydrophilicity profile of Figure 5; (XX) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9,10,11, 12,13,14,15,16,17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3B, 3C, and/or 3D in any whole number increment up to 1054, 1347, and/or 1337 respectively that includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,14,15, 16, 17, 18,19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value less than 0.5 in the Hydropathicity profile of Figure 6; (XXI) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9,10,11, 12,13, 14,15,16,17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3B, 3C, and or 3D in any whole number increment up to 1054, 1347, and/or 1337 respectively that includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13,14, 15,16,17,18,19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Percent Accessible Residues profile of Figure 7; (XXII) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9,10, 11, 12, 13, 14,15,16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3B, 30, and/or 3D in any whole number increment up to 1054, 1347, and/or 1337 respectively that includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Average Flexibility profile of Figure 8; (XXIII) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8,9,10, 11,12,13,14,15,16,17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3B, 3C, and/or 3D in any whole number increment up to 1054, 1347, and/or 1337 respectively that includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,14, 15,16,17,18,19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Beta-turn profile of Figure 9; (XXIV) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9,10, 11, 12,13,14,15,16,17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3E, 3F, 3G, 3H and/or 31 in any whole number increment up to 1310, 1037, 1048, 1340, and/or 1037 respectively that includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Hydrophilicity profile of Figure 5; (XXV) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3E, 3F, 3G, 3H and/or 31 in any whole number increment up to 1310, 1037, 1048, 1340, and/or 1037 respectively that includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11, 12,13,14,15,16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value less than 0.5 in the Hydropathicity profile of Figure 6; WO 2004/098515 PCT/US2004/013568 23 (XXVI) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3E, 3F, 3G, 3H and/or 31 in any whole number increment up to 1310, 1037, 1048, 1340, and/or 1037 respectively that includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Percent Accessible Residues profile of Figure 7; (XXVII) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9, 10, 11, 12, 13,14, 15,16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3E, 3F, 3G, 3H and/or 31 in any whole number increment up to 1310, 1037, 1048, 1340, and/or 1037 respectively that includes 1, 2, 3, 4, 5, 6, 7, 8, 9,10,11, 12,13,14,15,16,17,18,19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Average Flexibility profile of Figure 8; (XXVIII) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3E, 3F, 3G, 3H, and/or 31 in any whole number increment up to 1310, 1037, 1048, 1340, and/or 1037 respectively that includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11, 12,13,14,15,16, 17,18,19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Beta-turn profile of Figure 9; (XXIX) a polynucleotide that is fully complementary to a polynucleotide of any one of (I)-(XXVIII); (XXX) a polynucleotide that is fully complementary to a polynucleotide of any one of (l)-(XXIX); (XXXI) a peptide that is encoded by any of (1) to (XXX); and; (XXXII) a composition comprising a polynucleotide of any of (l)-(XXX) or peptide of (XXXI) together with a pharmaceutical excipient and/or in a human unit dose form; (XXX1I1) a method of using a polynucleotide of any (l)-(XXX) or peptide of (XXXI) or a composition of (XXXII) in a method to modulate a cell expressing 109P1 D4; (XXXIV) a method of using a polynucleotide of any (I)-(XXX) or peptide of (XXXI) or a composition of (XXXII) in a method to diagnose, prophylax, prognose, or treat an individual who bears a cell expressing 109P1 D4; (XXXV) a method of using a polynucleotide of any (I)-(XXX) or peptide of (XXXI) or a composition of (XXXII) in a method to diagnose, prophylax, prognose, or treat an individual who bears a cell expressing 109P1 D4, said cell from a cancer of a tissue listed in Table I; (XXXVI) a method of using a polynucleotide of any (I)-(XXX) or peptide of (XXXI) or a composition of (XXXII) in a method to diagnose, prophylax, prognose, or treat a a cancer; (XXXVII) a method of using a polynucleotide of any (I)-(XXX) or peptide of (XXXI) or a composition of (XXXII) in a method to diagnose, prophylax, prognose, or treat a a cancer of a tissue listed in Table I; and; (XXXVlll) a method of using a polynucleotide of any (I)-(XXX) or peptide of (XXXI) or a composition of (XXXII) in a method to identify or characterize a modulator of a cell expressing 109P1 D4. As used herein, a range is understood to disclose specifically all whole unit positions thereof. Typical embodiments of the invention disclosed herein include 109P1 D4 polynucleotides that encode specific portions of 109P1 D4 mRNA sequences (and those which are complementary to such sequences) such as those that encode the proteins and/or fragments thereof, for example: .

WO 2004/098515 PCT/US2004/013568 24 (a) 4,5,6, 7,8,9,10,11,12,13,14,15,16,17,18,19,20,21, 22,23, 24, 25, 30, 35, 40,45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95,100,105,110,115,120,125,130,135,140,145,150,155,160,165,170, 175,180,185,190,195, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 575, 600, 625, 650, 675, 700, 725, 750, 775, 800, 825, 850, 875, 900, 925, 950, 975, 1000, 1010, 1020, and 1021 or more contiguous amino acids of 109P1D4 variant 1; the maximal lengths relevant for other variants are: variant 2, 1054 amino acids; variant 3, 1347 amino acids, variant 4, 1337 amino acids, variant 5,1310 amino acids, variant 6; 1047 amino acids, variant 7; 1048 amino acids, variant 8; 1340 amino acids and variant 9; 1037 amoni acids. For example, representative embodiments of the invention disclosed herein include: polynucleotides and their encoded peptides themselves encoding about amino acid 1 to about amino acid 10 of the 109P1D4 protein shown in Figure 2 or Figure 3, polynucleotides encoding about amino acid 10 to about amino acid 20 of the 109P1 D4 protein shown in Figure 2 or Figure 3, polynucleotides encoding about amino acid 20 to about amino acid 30 of the 109P1 D4 protein shown in Figure 2 or Figure 3, polynucleotides encoding about amino acid 30 to about amino acid 40 of the 109P1 D4 protein shown in Figure 2 or Figure 3, polynucleotides encoding about amino acid 40 to about amino acid 50 of the 109P1 D4 protein shown in Figure 2 or Figure 3, polynucleotides encoding about amino acid 50 to about amino acid 60 of the 109P1 D4 protein shown in Figure 2 or Figure 3, polynucleotides encoding about amino acid 60 to about amino acid 70 of the 109P1 D4 protein shown in Figure 2 or Figure 3, polynucleoides encoding about amino acid 70 to about amino acid 80 of the 109P1 D4 protein shown in Figure 2 or Figure 3, polynucleotides encoding about amino acid 80 to about amino acid 90 of the 109P1 D4 protein shown in Figure 2 or Figure 3, polynucleoides encoding about amino acid 90 to about amino acid 100 of the 109P1 D4 protein shown in Figure 2 or Figure 3, in increments of about 10 amino acids, ending at the carboxyl terminal amino acid set forth in Figure 2 or Figure 3. Accordingly, polynucleotides encoding portions of the amino acid sequence (of about 10 amino acids), of amino acids, 100 through the carboxyl terminal amino acid of the 109P1D4 protein are embodiments of the invention. Wherein it is understood that each particular amino acid position discloses that position plus or minus five amino acid residues. Polynucleotides encoding relatively long portions of a 109P1 D4 protein are also within the scope of the invention. For example, polynucleotides encoding from about amino acid 1 (or 20 or 30 or 40 etc.) to about amino acid 20, (or 30, or 40 or 50 etc.) of the 109P1 D4 protein "or variant" shown in Figure 2 or Figure 3 can be generated by a variety of techniques well known in the art. These polynucleotide fragments can include any portion of the I 09P1 D4 sequence as shown in Figure 2. Additional illustrative embodiments of the invention disclosed herein include 109P1 D4 polynucleotide fragments encoding one or more of the biological motifs contained within a 109P1 D4 protein "or variant' sequence, including one or more of the motif-bearing subsequences of a 109P1D4 protein "or variant" set forth in Tables VIII-XXI and XXII-XLIX. In another embodiment, typical polynucleotide fragments of the invention encode one or more of the regions of 109P1 D4 protein or variant that exhibit homology to a known molecule. In another embodiment of the invention, typical polynucleotide fragments can encode one or more of the 109P1 D4 protein or variant N-glycosylation sites, cAMP and cGMP-dependent protein kinase phosphorylation sites, casein kinase 11 phosphorylation sites or N-myristoylation site and amidation sites. Note that to determine the starting position of any peptide set forth in Tables VIllI-XXI and Tables XXII to XLIX (collectively HLA Peptide Tables) respective to its parental protein, e.g., variant 1, variant 2, etc., reference is made to three factors: the particular variant, the length of the peptide in an HLA Peptide Table, and the Search Peptides listed in Table VII. Generally, a unique Search Peptide is used to obtain HLA peptides for a particular variant. The position of each Search Peptide relative to its respective parent molecule is listed in Table VII. Accordingly, if a Search Peptide begins at position "X", one must add the value "X minus 1" to each position in Tables VIII-XXI and Tables XXII-IL to obtain the actual position of the HLA peptides in their parental molecule. For example if a particular Search Peptide begins at position 150 of its parental molecule, one must add 150 -1, i.e., 149 to each HLA peptide amino acid position to calculate the position of that amino acid WO 2004/098515 PCT/US2004/013568 25 in the parent molecule. II.A.) Uses of 109P1 D4 Polynucleotides Il.A.1.) Monitoring of Genetic Abnormalities The polynucleotides of the preceding paragraphs have a number of different specific uses. The human 109P1 D4 gene maps to the chromosomal location set forth in the Example entitled "Chromosomal Mapping of 109P1 D4." For example, because the 109P1D4 gene maps to this chromosome, polynucleotides that encode different regions of the 109P1 D4 proteins are used to characterize cytogenetic abnormalities of this chromosomal locale, such as abnormalities that are identified as being associated with various cancers. In certain genes, a variety of chromosomal abnormalities including rearrangements have been identified as frequent cytogenetic abnormalities in a number of different cancers (see e.g. Krajinovic et al., Mutat. Res. 382(3-4): 81-83 (1998); Johansson et al., Blood 86(10): 3905-3914 (1995) and Finger et al., P.N.A.S. 85(23): 9158-9162 (1988)). Thus, polynucleotides encoding specific regions of the 109P1D4 proteins provide new tools that can be used to delineate, with greater precision than previously possible, cytogenetic abnormalities in the chromosomal region that encodes 109P1 D4 that may contribute to the malignant phenotype. In this context, these polynucleotides satisfy a need in the art for expanding the sensitivity of chromosomal screening in order to identify more subtle and less common chromosomal abnormalities (see e.g. Evans et al., Am. J. Obstet. Gynecol 171(4): 1055-1057 (1994)). Furthermore, as 109P1 D4 was shown to be highly expressed in prostate and other cancers, 109P1 D4 polynucleotides are used in methods assessing the status of 109P1D4 gene products in normal versus cancerous tissues. Typically, polynucleotides that encode specific regions of the 109P1 D4 proteins are used to assess the presence of perturbations (such as deletions, insertions, point mutations, or alterations resulting in a loss of an antigen etc.) in specific regions of the 109P1D4 gene, such as regions containing one or more motifs. Exemplary assays include both RT-PCR assays as well as single-strand conformation polymorphism (SSCP) analysis (see, e.g., Marrogi et al., J. Cutan. Pathol. 26(8): 369-378 (1999), both of which utilize polynucleotides encoding specific regions of a protein to examine these regions within the protein. IL.A.2.) Antisense Embodiments Other specifically contemplated nucleic acid related embodiments of the invention disclosed herein are genomic DNA, cDNAs, ribozymes, and antisense molecules, as well as nucleic acid molecules based on an alternative backbone, or including alternative bases, whether derived from natural sources or synthesized, and include molecules capable of inhibiting the RNA or protein expression of109P1D4. For example, antisense molecules can be RNAs or other molecules, including peptide nucleic acids (PNAs) or non-nucleic acid molecules such as phosphorothioate derivatives that specifically bind DNA or RNA in a base pair-dependent manner. A skilled artisan can readily obtain these classes of nucleic acid molecules using the 1 09P1 D4 polynucleotides and polynucleotide sequences disclosed herein. Antisense technology entails the administration of exogenous oligonucleotides that bind to a target polynucleotide located within the cells. The term "antisense" refers to the fact that such oligonucleotides are complementary to their intracellular targets, e.g., 109P1 D4. See for example, Jack Cohen, Oligodeoxynucleotides, Antisense Inhibitors of Gene Expression, CRC Press, 1989; and Synthesis 1:1-5 (1988). The 109P1D4 antisense oligonucleotides of the present invention include derivatives such as S-oligonucleotides (phosphorothioate derivatives or S-oligos, see, Jack Cohen, supra), which exhibit enhanced cancer cell growth inhibitory action. S-oligos (nucleoside phosphorothioates) are isoelectronic analogs of an oligonucleotide (0-oligo) in which a nonbridging oxygen atom of the phosphate group is replaced by a sulfur atom. The S-oligos of the present invention can be prepared by treatment of the corresponding 0-oligos with 3H-1,2 benzodithiol-3-one-1,1-dioxide, which is a sulfur transfer reagent. See, e.g., lyer, R. P. et aL., J. Org. Chem. 55:4693-4698 WO 2004/098515 PCT/US2004/013568 26 (1990); and lyer, R. P. et a., J. Am. Chem. Soc. 112:1253-1254 (1990). Additional 109P1 D4 antisense oligonucleotides of the present invention include morpholino antisense oligonucleotides known in the art (see, e.g., Partridge et a., 1996, Antisense & Nucleic Acid Drug Development 6: 169-175). The 109P1 D4 antisense oligonucleotides of the present invention typically can be RNA or DNA that is complementary to and stably hybridizes with the first 100 5' codons or last 100 3' codons of a 109P1D4 genomic sequence or the corresponding mRNA. Absolute complementarity is not required, although high degrees of complementarity are preferred. Use of an oligonucleotide complementary to this region allows for the selective hybridization to 109P1D4 mRNA and not to mRNA specifying other regulatory subunits of protein kinase. In one embodiment, 10921D4 antisense oligonucleotides of the present invention are 15 to 30-mer fragments of the antisense DNA molecule that have a sequence that hybridizes to 109P1 D4 mRNA. Optionally, 109P1 D4 antisense oligonucleotide is a 30-mer oligonucleotide that is complementary to a region in the first 10 5' codons or last 10 3' codons of 109P1D4. Alternatively, the antisense molecules are modified to employ ribozymes in the inhibition of 109P1 D4 expression, see, e.g., L. A. Couture & D. T. Stinchcomb; Trends Genet 12: 510-515 (1996). II.A.3.) Primers and Primer Pairs Further specific embodiments of these nucleotides of the invention include primers and primer pairs, which allow the specific amplification of polynucleotides of the invention or of any specific parts thereof, and probes that selectively or specifically hybridize to nucleic acid molecules of the invention or to any part thereof. Probes can be labeled with a detectable marker, such as, for example, a radioisotope, fluorescent compound, bioluminescent compound, a chemiluminescent compound, metal chelator or enzyme. Such probes and primers are used to detect the presence of a 109P1D4 polynucleotide in a sample and as a means for detecting a cell expressing a 109P1D4 protein. Examples of such probes include polypeptides comprising all or part of the human 109P1D4 cDNA sequence shown in Figure 2. Examples of primer pairs capable of specifically amplifying 109P1D4 mRNAs are also described in the Examples. As will be understood by the skilled artisan, a great many different primers and probes can be prepared based on the sequences provided herein and used effectively to amplify and/or detect a 109P1D4 mRNA. The 109P1D4 polynucleotides of the invention are useful for a variety of purposes, including but not limited to their use as probes and primers for the amplification and/or detection of the 109P1D4 gene(s), mRNA(s), or fragments thereof; as reagents for the diagnosis and/or prognosis of prostate cancer and other cancers; as coding sequences capable of directing the expression of 109P1D4 polypeptides; as tools for modulating or inhibiting the expression of the 109P1D4 gene(s) and/or translation of the 109P1D4 transcript(s); and as therapeutic agents. The present invention includes the use of any probe as described herein to identify and isolate a 109P1D4 or 109P1D4 related nucleic acid sequence from a naturally occurring source, such as humans or other mammals, as well as the isolated nucleic acid sequence per se, which would comprise all or most of the sequences found in the probe used. II.A.4.) Isolation of I09PID4-Encoding Nucleic Acid Molecules The 109P1D4 cDNA sequences described herein enable the isolation of other polynucleotides encoding 109P1D4 gene product(s), as well as the isolation of polynucleotides encoding 109P1D4 gene product homologs, alternatively spliced isoforms, allelic variants, and mutant forms of a 109P1D4 gene product as well as polynucleotides that encode analogs of 109P1D4-related proteins. Various molecular cloning methods that can be employed to isolate full length cDNAs encoding a 109P1D4 gene are well known (see, for example, Sambrook, J. et al., Molecular Cloning: A Laboratory Manual, 2d edition, Cold Spring Harbor Press, New York, 1989; Current Protocols in Molecular Biology. Ausubel et a., Eds., Wiley and Sons, 1995). For example, lambda phage cloning methodologies can be conveniently employed, using commercially available cloning systems (e.g., Lambda ZAP Express, Stratagene). Phage clones containing 109P1D4 gene cDNAs can be identified by probing with a labeled 109P1D4 WO 2004/098515 PCT/US2004/013568 27 cDNA or a fragment thereof. For example, in one embodiment, a 1 09P1 D4 cDNA (e.g., Figure 2) or a portion thereof can be synthesized and used as a probe to retrieve overlapping and full-length cDNAs corresponding to a 109P1 D4 gene. A 109P1 D4 gene itself can be isolated by screening genomic DNA libraries, bacterial artificial chromosome libraries (BACs), yeast artificial chromosome libraries (YACs), and the like, with 109P1 D4 DNA probes or primers. II.A.5.) Recombinant Nucleic Acid Molecules and Host-Vector Systems The invention also provides recombinant DNA or RNA molecules containing a 109P1 D4 polynucleotide, a fragment, analog or homologue thereof, including but not limited to phages, plasmids, phagemids, cosmids, YACs, BACs, as well as various viral and non-viral vectors well known in the art, and cells transformed or transfected with such recombinant DNA or RNA molecules. Methods for generating such molecules are well known (see, for example, Sambrook et aL, 1989, supra). The invention further provides a host-vector system comprising a recombinant DNA molecule containing a 109P1 D4 polynucleotide, fragment, analog or homologue thereof within a suitable prokaryotic or eukaryotic host cell. Examples of suitable eukaryotic host cells include a yeast cell, a plant cell, or an animal cell, such as a mammalian cell or an insect cell (e.g., a baculovirus-infectible cell such as an Sf9 or HighFive cell). Examples of suitable mammalian cells include various prostate cancer cell lines such as DU145 and TsuPr1, other transfectable or transducible prostate cancer cell lines, primary cells (PrEC), as well as a number of mammalian cells routinely used for the expression of recombinant proteins (e.g., COS, CHO, 293, 293T cells). More particularly, a polynucleotide comprising the coding sequence of 109P1D4 or a fragment, analog or homolog thereof can be used to generate 109P1 D4 proteins or fragments thereof using any number of host-vector systems routinely used and widely known in the art. A wide range of host-vector systems suitable for the expression of 109P1 D4 proteins or fragments thereof are available, see for example, Sambrook et aL, 1989, supra; Current Protocols in Molecular Biology, 1995, supra). Preferred vectors for mammalian expression include but are not limited to pcDNA 3.1 myc-His-tag (Invitrogen) and the retroviral vector pSRatkneo (Muller et al., 1991, MCB 11:1785). Using these expression vectors, 1109P1 D4 can be expressed in several prostate cancer and non-prostate cell lines, including for example 293, 293T, rat-1, NIH 3T3 and TsuPr1. The host-vector systems of the invention are useful for the production of a 109P1 D4 protein or fragment thereof. Such host-vector systems can be employed to study the functional properties of 109P1D4 and 109P1D4 mutations or analogs. Recombinant human 109P1 D4 protein or an analog or homolog or fragment thereof can be produced by mammalian cells transfected with a construct encoding a 109P1 D4-related nucleotide. For example, 293T cells can be transfected with an expression plasmid encoding 109P1 D4 or fragment, analog or homolog thereof, a 109P1 D4-related protein is expressed in the 293T cells, and the recombinant 109P1D4 protein is isolated using standard purification methods (e.g., affinity purification using anti-1 09P1 D4 antibodies). In another embodiment, a 109P1 D4 coding sequence is subcloned into the retroviral vector pSRaMSVtkneo and used to infect various mammalian cell lines, such as NIH 3T3, TsuPrl, 293 and rat-1 in order to establish 109P1 D4 expressing cell lines. Various other expression systems well known in the art can also be employed. Expression constructs encoding a leader peptide joined in frame to a 109P1 D4 coding sequence can be used for the generation of a secreted form of recombinant 109P1 D4 protein. As discussed herein, redundancy in the genetic code permits variation in 109P1D4 gene sequences. In particular, it is known in the art that specific host species often have specific codon preferences, and thus one can adapt the disclosed sequence as preferred for a desired host, For example, preferred analog codon sequences typically have rare codons (i.e., codons having a usage frequency of less than about 20% in known sequences of the desired host) replaced with higher frequency codons. Codon preferences for a specific species are calculated, for example, by utilizing codon usage tables available on the INTERNET such as at URL dna.affrc.go.jp/-nakamura/codon.html. Additional sequence modifications are known to enhance protein expression in a cellular host. These include WO 2004/098515 PCT/US2004/013568 28 elimination of sequences encoding spurious polyadenylation signals, exonlintron splice site signals, transposon-like repeats, and/or other such well-characterized sequences that are deleterious to gene expression. The GC content of the sequence is adjusted to levels average for a given cellular host, as calculated by reference to known genes expressed in the host cell. Where possible, the sequence is modified to avoid predicted hairpin secondary mRNA structures. Other useful modifications include the addition of a translational initiation consensus sequence at the start of the open reading frame, as described in Kozak, Mol. Cell Biol., 9:5073-5080 (1989). Skilled artisans understand that the general rule that eukaryotic ribosomes initiate translation exclusively at the 5' proximal AUG codon is abrogated only under rare conditions (see, e.g., Kozak PNAS 92(7): 2662-2666, (1995) and Kozak NAR 15(20): 8125-8148 (1987)). Ili.) 109P1D4-related Proteins Another aspect of the present invention provides 109P1 4-related proteins. Specific embodiments of 109P1 D4 proteins comprise a polypeptide having all or part of the amino acid sequence of human 109P1 D4 as shown in Figure 2 or Figure 3. Alternatively, embodiments of 109P1D4 proteins comprise variant, homolog or analog polypeptides that have alterations in the amino acid sequence of 109P1D4 shown in Figure 2 or Figure 3. Embodiments of a 109P1 D4 polypeptide include: a 109P1 D4 polypeptide having a sequence shown in Figure 2, a peptide sequence of a 109P1 D4 as shown in Figure 2 wherein T is U; at least 10 contiguous nucleotides of a polypeptide having the sequence as shown in Figure 2; or, at least 10 contiguous peptides of a polypeptide having the sequence as shown in Figure 2 where T is U. For example, embodiments of 109P1 D4 peptides comprise, without limitation: (I) a protein comprising, consisting essentially of, or consisting of an amino acid sequence as shown in Figure 2A-1 or Figure 3A-1; (11) a 109P1D4-related protein that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% homologous to an entire amino acid sequence shown in Figure 2A-l or 3A-1; (II) a 109P1 D4-related protein that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% identical to an entire amino acid sequence shown in Figure 2A-1 or 3A-1; (IV) a protein that comprises at least one peptide set forth in Tables Vill to XLIX, optionally with a proviso that it is not an entire protein of Figure 2; (V) a protein that comprises at least one peptide set forth in Tables VIll-XXI, collectively, which peptide is also set forth in Tables XXII to XLIX, collectively, optionally with a proviso that it is not an entire protein of Figure 2; (VI) a protein that comprises at least two peptides selected from the peptides set forth in Tables VIII-XLIX, optionally with a proviso that it is not an entire protein of Figure 2; (VII) a protein that comprises at least two peptides selected from the peptides set forth in Tables Vill to XLIX collectively, with a proviso that the protein is not a contiguous sequence from an amino acid sequence of Figure 2; (Vill) a protein that comprises at least one peptide selected from the peptides set forth in Tables VIII-XXI; and at least one peptide selected from the peptides set forth in Tables XXII to XLIX, with a proviso that the protein is not a contiguous sequence from an amino acid sequence of Figure 2; (IX) a polypeptide comprising at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a protein of Figure 3A, 3B, 3C, 3D and/or 3E in any whole number increment up to 1021, 1054, 1347, 1337, and/or 1310 respectively that includes at least 1, 2, 3, 4, 5, WO 2004/098515 PCT/US2004/013568 29 6,7, 8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Hydrophilicity profile of Figure 5; (X) a polypeptide comprising at least 5, 6, 7, 8, 9,10,11, 12,13,14,15,16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a protein of Figure 3A, 3B, 3C, 3D, and/or 3E, in any whole number increment up to 1021, 1054, 1347, 1337, and/or 1310 respectively respectively that includes at least at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value less than 0.5 in the Hydropathicity profile of Figure 6; (XI) a polypeptide comprising at least 5, 6, 7, 8, 9, 10,11, 12,13,14,15,16,17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a protein of Figure 3A, 3B, 3C, 3D, and/or 3E, in any whole number increment up to 1021, 1054, 1347, 1337, and/or 1310 respectively respectively that includes at least at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Percent Accessible Residues profile of Figure 7; (XII) a polypeptide comprising at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a protein of Figure 3A, 3B, 3C, 3D, and/or 3E, in any whole number increment up to 1021, 1054, 1347, 1337, and/or 1310 respectively respectively that includes at least at least 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12,13,14,15,16, 17,18,19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Average Flexibility profile of Figure 8; (XIII) a polypeptide comprising at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, amino acids of a protein of Figure 3A, 3B, 3C, 3D, and 3E in any whole number increment up to 1021, 1054, 1347, 1337, and/or 1310 respectively respectively that includes at least at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Beta-turn profile of Figure 9; (XIV) a polypeptide comprising at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16,17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a protein of Figure 3F, 3G, 3H, and/or 31, in any whole number increment up to 1037, 1048, 1340, and/or 1037 respectively that includes at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Hydrophilicity profile of Figure 5; (XV) a polypeptide comprising at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a protein of Figure 3F, 3G, 3H, and/or 31 in any whole number increment up to 1037, 1048, 1340, and/or 1037 respectively that includes at least at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value less than 0.5 in the Hydropathicity profile of Figure 6; (XVI) a polypeptide comprising at least 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a protein of Figure 3F, 3G, 3H, and/or 31 in any whole number increment up to 1037, 1048, 1340, and/or 1037 respectively that includes at least at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Percent Accessible Residues profile of Figure 7; (XVIl) a polypeptide comprising at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, WO 2004/098515 PCT/US2004/013568 30 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a protein of Figure 3F, 3G, 3H, and/or 31 in any whole number increment up to 1037, 1048, 1340, and/or 1037 respectively that includes at least at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Average Flexibility profile of Figure 8; (XVIII) a polypeptide comprising at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18,19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, amino acids of a protein of Figure 3F, 3G, 3H, and/or 31 in any whole number increment up to 1037, 1048, 1340, and/or 1037 respectively that includes at least at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, 17, 18,19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Beta-turn profile of Figure 9; (XIX) a peptide that occurs at least twice in Tables VIII-XXI and XXII to XLIX, collectively; (XX) a peptide that occurs at least three times in Tables VIII-XXI and XXII to XLIX, collectively; (XXI) a peptide that occurs at least four times in Tables VIII-XXI and XXII to XLIX, collectively; (XXII) a peptide that occurs at least five times in Tables VIlI-XXI and XXII to XLIX, collectively; (XXIII) a peptide that occurs at least once in Tables Villi-XXI, and at least once in tables XXII to XLIX; (XXIV) a peptide that occurs at least once in Tables VIII-XXI, and at least twice in tables XXII to XLIX; (XXV) a peptide that occurs at least twice in Tables VIlI-XXI, and at least once in tables XXII to XLIX; (XXVI) a peptide that occurs at least twice in Tables Vill-XXI, and at least twice in tables XXII to XLIX; (XXVII) a peptide which comprises one two, three, four, or five of the following characteristics, or an oligonucleotide encoding such peptide: i) a region of at least 5 amino acids of a particular peptide of Figure 3, in any whole number increment up to the full length of that protein in Figure 3, that includes an amino acid position having a value equal to or greater than 0.5, 0.6, 0.7, 0.8, 0.9, or having a value equal to 1.0, in the Hydrophilicity profile of Figure 5; ii) a region of at least 5 amino acids of a particular peptide of Figure 3, in any whole number Increment up to the full length of that protein in Figure 3, that includes an amino acid position having a value equal to or less than 0.5, 0.4, 0.3, 0.2, 0.1, or having a value equal to 0.0, in the Hydropathicity profile of Figure 6; iii) a region of at least 5 amino acids of a particular peptide of Figure 3, in any whole number increment up to the full length of that protein in Figure 3, that includes an amino acid position having a value equal to or greater than 0.5, 0.6, 0.7, 0.8, 0.9, or having a value equal to 1.0, in the Percent Accessible Residues profile of Figure 7; iv) a region of at least 5 amino acids of a particular peptide of Figure 3, in any whole number increment up to the full length of that protein in Figure 3, that includes an amino acid position having a value equal to or greater than 0.5, 0.6, 0.7, 0.8, 0.9, or having a value equal to 1.0, in the Average Flexibility profile of Figure 8; or, v) a region of at least 5 amino acids of a particular peptide of Figure 3, in any whole number increment up to the full length of that protein in Figure 3, that includes an amino acid position having a value equal to or greater than 0.5, 0.6, 0.7, 0.8, 0.9, or having a value equal to 1.0, in the Beta-turn profile of Figure 9;; (XXVIII) a composition comprising a peptide of (I)-(XXVII) or an antibody or binding region thereof together with a pharmaceutical excipient and/or in a human unit dose form.

WO 2004/098515 PCT/US2004/013568 31 (XXIX) a method of using a peptide of (I)-(XXVII), or an antibody or binding region thereof or a composition of (XXVIII) in a method to modulate a cell expressing 109P1D4,; (XXX) a method of using a peptide of (I)-(XXVII) or an antibody or binding region thereof or a composition of (XXVIII) in a method to diagnose, prophylax, prognose, or treat an individual who bears a cell expressing 109P1D4; (XXXI) a method of using a peptide of (I)-(XXVII) or an antibody or binding region thereof or a composition (XXVIII) in a method to diagnose, prophylax, prognose, or treat an individual who bears a cell expressing 109P1D4, said cell from a cancer of a tissue listed in Table I; (XXXII) a method of using a peptide of (I)-(XXVII) or an antibody or binding region thereof or a composition of (XXVIII) in a method to diagnose, prophylax, prognose, or treat a a cancer; (XXXIII) a method of using a peptide of (l)-(XXVII) or an antibody or binding region thereof or a composition of (XXVIII) in a method to diagnose, prophylax, prognose, or treat a a cancer of a tissue listed in Table I; and; (XXXIV) a method of using a a peptide of (I)-(XXVII) or an antibody or binding region thereof or a composition (XXVIII) in a method to identify or characterize a modulator of a cell expressing 109P1D4 As used herein, a range is understood to specifically disclose all whole unit positions thereof. Typical embodiments of the invention disclosed herein include 109P1 D4 polynucleotides that encode specific portions of 109P1 D4 mRNA sequences (and those which are complementary to such sequences) such as those that encode the proteins and/or fragments thereof, for example: (a) 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 575, 600, 625, 650, 675, 700, 725, 750, 775, 800, 825, 850, 875, 900, 925, 950, 975, 1000, 1010, 1020, and 1021 or more contiguous amino acids of 109P1D4 variant 1; the maximal lengths relevant for other variants are: variant 2, 1054 amino acids; variant 3, 1347 amino acids, variant 4, 1337 amino acids, variant 5, 1310 amino acids, variant 6; 1037 amino acids, variant 7; 1048 amino acids, variant 8; 1340 amino acids, and variant 9; 1037 amino acids.. In general, naturally occurring allelic variants of human 109P1 D4 share a high degree of structural identity and homology (e.g., 90% or more homology), Typically, allelic variants of a 109P1 D4 protein contain conservative amino acid substitutions within the 109P1 D4 sequences described herein or contain a substitution of an amino acid from a corresponding position in a homologue of 109P1 D4. One class of 109P1D4 allelic variants are proteins that share a high degree of homology with at least a small region of a particular 109P1 D4 amino acid sequence, but further contain a radical departure from the sequence, such as a non-conservative substitution, truncation, insertion or frame shift. In comparisons of protein sequences, the terms, similarity, identity, and homology each have a distinct meaning as appreciated in the field of genetics. Moreover, orthology and paralogy can be important concepts describing the relationship of members of a given protein family in one organism to the members of the same family in other organisms. Amino acid abbreviations are provided in Table I. Conservative amino acid substitutions can frequently be made in a protein without altering either the conformation or the function of the protein. Proteins of the invention can comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 conservative substitutions. Such changes include substituting any of isoleucine (I), valine (V), and leucine (L) for any other of these hydrophobic amino acids; aspartic acid (D) for glutamic acid (E) and vice versa; glutamine (Q) for asparagine (N) and vice versa; and serine (S) for threonine (T) and vice versa. Other substitutions WO 2004/098515 PCT/US2004/013568 32 can also be considered conservative, depending on the environment of the particular amino acid and its role in the three dimensional structure of the protein. For example, glycine (G) and alanine (A) can frequently be interchangeable, as can alanine (A) and valine (V). Methionine (M), which is relatively hydrophobic, can frequently be interchanged with leucine and isoleucine, and sometimes with valine. Lysine (K) and arginine (R) are frequently interchangeable in locations in which the significant feature of the amino acid residue is its charge and the differing pKs of these two amino acid residues are not significant. Still other changes can be considered "conservative" in particular environments (see, e.g. Table IlI herein; pages 13-15 "Biochemistry" 2nd ED, Lubert Stryer ed (Stanford University); Henikoff et al., PNAS 1992 Vol 89 10915-10919; Lei et al., J Biol Chem 1995 May 19; 270(20):11882-6). Embodiments of the invention disclosed herein include a wide variety of art-accepted variants or analogs of 109P1D4 proteins such as polypeptides having amino acid insertions, deletions and substitutions. 109P1D4 variants can be made using methods known in the art such as site-directed mutagenesis, alanine scanning, and PCR mutagenesis. Site directed mutagenesis (Carter et al., Nucl. Acids Res., 13:4331 (1986); Zoller et al., Nucl. Acids Res., 10:6487 (1987)), cassette mutagenesis (Wells et aL, Gene, 34:315 (1985)), restriction selection mutagenesis (Wells et al., Philos. Trans. R. Soc. London SerA, 317:415 (1986)) or other known techniques can be performed on the cloned DNA to produce the 109P1D4 variant DNA. Scanning amino acid analysis can also be employed to identify one or more amino acids along a contiguous sequence that is involved in a specific biological activity such as a protein-protein interaction. Among the preferred scanning amino acids are relatively small, neutral amino acids. Such amino acids include alanine, glycine, serine, and cysteine. Alanine is typically a preferred scanning amino acid among this group because it eliminates the side-chain beyond the beta carbon and is less likely to alter the main-chain conformation of the variant. Alanine is also typically preferred because it is the most common amino acid. Further, it is frequently found in both buried and exposed positions (Creighton, The Proteins, (W.H. Freeman & Co., N.Y.); Chothia, J. Mol. Biol., 150:1 (1976)). If alanine substitution does not yield adequate amounts of variant, an isosteric amino acid can be used. As defined herein, 109P1D4 variants, analogs or homologs, have the distinguishing attribute of having at least one epitope that is "cross reactive" with a 109P1D4 protein having an amino acid sequence of Figure 3. As used in this sentence, "cross reactive" means that an antibody or T cell that specifically binds to a 1 09P1 D4 variant also specifically binds to a 109P1 D4 protein having an amino acid sequence set forth in Figure 3. A polypeptide ceases to be a variant of a protein shown in Figure 3, when it no longer contains any epitope capable of being recognized by an antibody or T cell that specifically binds to the starting 109P1D4 protein. Those skilled in the art understand that antibodies that recognize proteins bind to epitopes of varying size, and a grouping of the order of about four or five amino acids, contiguous or not, is regarded as a typical number of amino acids in a minimal epitope. See, e.g., Nair et al., J. Immunol 2000 165(12): 6949-6955; Hebbes et al., Mol Immunol (1989) 26(9):865-73; Schwartz et al., J Immunol (1985) 135(4):2598-608. Other classes of 1 09P1 D4-related protein variants share 70%, 75%, 80%, 85% or 90% or more similarity with an amino acid sequence of Figure 3, or a fragment thereof. Another specific class of 109P1D4 protein variants or analogs comprises one or more of the 109P1D4 biological motifs described herein or presently known in the art. Thus, encompassed by the present invention are analogs of 109P1D4 fragments (nucleic or amino acid) that have altered functional (e.g. immunogenic) properties relative to the starting fragment. It is to be appreciated that motifs now or which become part of the art are to be applied to the nucleic or amino acid sequences of Figure 2 or Figure 3. As discussed herein, embodiments of the claimed invention include polypeptides containing less than the full amino acid sequence of a 109P1 D4 protein shown in Figure 2 or Figure 3. For example, representative embodiments of the invention comprise peptides/proteins having any 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more contiguous amino acids of a WO 2004/098515 PCT/US2004/013568 33 109P1 D4 protein shown in Figure 2 or Figure 3. Moreover, representative embodiments of the invention disclosed herein include polypeptides consisting of about amino acid I to about amino acid 10 of a 109P1D4 protein shown in Figure 2 or Figure 3, polypeptides consisting of about amino acid 10 to about amino acid 20 of a 109P1D4 protein shown in Figure 2 or Figure 3, polypeptides consisting of about amino acid 20 to about amino acid 30 of a 109P1 D4 protein shown in Figure 2 or Figure 3, polypeptides consisting of about amino acid 30 to about amino acid 40 of a 109P1 D4 protein shown in Figure 2 or Figure 3, polypeptides consisting of about amino acid 40 to about amino acid 50 of a 109P1 D4 protein shown in Figure 2 or Figure 3, polypeptides consisting of about amino acid 50 to about amino acid 60 of a 1 09P1 D4 protein shown in Figure 2 or Figure 3, polypeptides consisting of about amino acid 60 to about amino acid 70 of a 109P1 D4 protein shown in Figure 2 or Figure 3, polypeptides consisting of about amino acid 70 to about amino acid 80 of a 109P1 D4 protein shown in Figure 2 or Figure 3, polypeptides consisting of about amino acid 80 to about amino acid 90 of a 109P1 D4 protein shown in Figure 2 or Figure 3, polypeptides consisting of about amino acid 90 to about amino acid 100 of a 109P1 D4 protein shown in Figure 2 or Figure 3, etc. throughout the entirety of a 109P1 D4 amino acid sequence. Moreover, polypeptides consisting of about amino acid 1 (or 20 or 30 or 40 etc.) to about amino acid 20, (or 130, or 140 or 150 etc.) of a 109P1D4 protein shown in Figure 2 or Figure 3 are embodiments of the invention. It is to be appreciated that the starting and stopping positions in this paragraph refer to the specified position as well as that position plus or minus 5 residues. 109P1 4-related proteins are generated using standard peptide synthesis technology or using chemical cleavage methods well known in the art Altematively, recombinant methods can be used to generate nucleic acid molecules that encode a 109P1 4-related protein. In one embodiment, nucleic acid molecules provide a means to generate defined fragments of a 109P1 D4 protein (or variants, homologs or analogs thereof). lIlA.) Motif-bearing Protein Embodiments Additional illustrative embodiments of the invention disclosed herein include 109P1 D4 polypeptides comprising the amino acid residues of one or more of the biological motifs contained within a 109P1 D4 polypeptide sequence set forth in Figure 2 or Figure 3. Various motifs are known in the art, and a protein can be evaluated for the presence of such motifs by a number of publicly available Internet sites (see, e.g., URL addresses: pfam.wustl.edu/; searchlauncher.bcm.tmc.edulseq search/struc-predict.html; psort.ims.u-tokyo.ac.jp/; cbs.dtu.dk/; ebi.ac.uk/interprolscan.htmi; expasy.ch/tools/scnpsitl.htmi; EpimatrixTM and Epimer

TM

, Brown University, brown.edu/Research/TB-HIVLabepimatrix/epimatrix.html; and BIMAS, bimas.dcrtnih.gov/.). Motif bearing subsequences of all 109P1D4 variant proteins are set forth and identified in Tables Vill-XXI and XXII XLIX. Table V sets forth several frequently occurring motifs based on pfam searches (see URL address pfam.wust.edu/). The columns of Table V list (1) motif name abbreviation, (2) percent identity found amongst the different member of the motif family, (3) motif name or description and (4) most common function; location information is included if the motif is relevant for location. Polypeptides comprising one or more of the 109P1 D4 motifs discussed above are useful in elucidating the specific characteristics of a malignant phenotype in view of the observation that the 109P1 D4 motifs discussed above are associated with growth dysregulation and because 109P1D4 is overexpressed in certain cancers (See, e.g., Table I). Casein kinase I1, cAMP and camp-dependent protein kinase, and Protein Kinase C, for example, are enzymes known to be associated with the development of the malignant phenotype (see e.g. Chen et aL., Lab Invest., 78(2): 165-174 (1998); Gaiddon et al., Endocrinology 136(10): 4331-4338 (1995); Hall et aL., Nucleic Acids Research 24(6): 1119-1126 (1996); Peterzie et al., Oncogene 18(46): 6322-6329 (1999) and O'Brian, Oncol. Rep. 5(2): 305-309 (1998)). Moreover, both glycosylation and WO 2004/098515 PCT/US2004/013568 34 myristoylation are protein modifications also associated with cancer and cancer progression (see e.g. Dennis at al., Biochem. Biophys. Acta 1473(1):21-34 (1999); Raju et al., Exp. Cell Res. 235(1): 145-154 (1997)). Amidation is another protein modification also associated with cancer and cancer progression (see e.g. Treston et al., J. NatI. Cancer Inst. Monogr. (13): 169-175 (1992)). In another embodiment, proteins of the invention comprise one or more of the immunoreactive epitopes identified in accordance with art-accepted methods, such as the peptides set forth in Tables VIII-XXI and XXII-XLIX. CTL epitopes can be determined using specific algorithms to identify peptdes within a 109P1 D4 protein that are capable of optimally binding to specified HLA alleles (e.g., Table IV; EpimatrixTM and Epimer T M , Brown University, URL brown.edu/Research/TB HI'Lab/epimatrix/epimatrix.html; and BIMAS, URL bimas.dcrt.nih.gov/.) Moreover, processes for identifying peptides that have sufficient binding affinity for HLA molecules and which are correlated with being immunogenic epitopes, are well known in the art, and are carried out without undue experimentation. In addition, processes for identifying peptides that are immunogenic epitopes, are well known in the art, and are carried out without undue experimentation either in vitro or in vivo. Also known in the art are principles for creating analogs of such epitopes in order to modulate immunogenicity. For example, one begins with an epitope that bears a CTL or HTL motif (see, e.g., the HLA Class I and HLA Class 1i motifs/supermotifs of Table IV). The epitope is analoged by substituting out an amino acid at one of the specified positions, and replacing it with another amino acid specified for that position. For example, on the basis of residues defined in Table IV, one can substitute out a deleterious residue in favor of any other residue, such as a preferred residue; substitute a less preferred residue with a preferred residue; or substitute an originally-occurring preferred residue with another preferred residue. Substitutions can occur at primary anchor positions or at other positions in a peptide; see,,e.g., Table IV. A variety of references reflect the art regarding the identification and generation of epitopes in a protein of interest as well as analogs thereof. See, for example, WO 97/33602 to Chesnut et al; Sette, Immunogenetics 1999 50(3-4): 201 212; Sette et aL., J. Immunol. 2001 166(2): 1389-1397; Sidney eta., Hum. Immunol. 1997 58(1): 12-20; Kondo et al., Immunogenetics 1997 45(4): 249-258; Sidney et al., J. Immunol. 1996 157(8): 3480-90; and Falk et aL., Nature 351: 290-6 (1991); Hunt et al, Science 255:1261-3 (1992); Parker et al., J. Immunol. 149:3580-7 (1992); Parker et al., J. Immunol. 152:163-75 (1994)); Kast et al, 1994 152(8): 3904-12; Borras-Cuesta et al., Hum. Immunol. 2000 61(3): 266-278; Alexander et al., J. Immunol. 2000 164(3); 164(3): 1625-1633; Alexander et al., PMID: 7895164, Ul: 95202582; O'Sullivan et a/, J. Immunol. 1991 147(8): 2663-2669; Alexander et al., Immunity 1994 1(9): 751-761 and Alexander et aL, Immunol. Res. 1998 18(2): 79-92. Related embodiments of the invention include polypeptides comprising combinations of the different motifs set forth in Table VI, and/or, one or more of the predicted CTL epitopes of Tables VIII-XXI and XXII-XLIX, and/or, one or more of the predicted HTL epitopes of Tables XLVI-XLIX, and/or, one or more of the T cell binding motifs known in the art. Preferred embodiments contain no insertions, deletions or substitutions either within the motifs or within the intervening sequences of the polypeptides. In addition, embodiments which include a number of either N-terminal and/or C-terminal amino acid residues on either side of these motifs may be desirable (to, for example, include a greater portion of the polypeptide architecture in which the motif is located). Typically, the number of N-terminal and/or C-terminal amino acid residues on either side of a motif is between about 1 to about 100 amino acid residues, preferably 5 to about 50 amino acid residues. 109P1D4-related proteins are embodied in many forms, preferably in isolated form. A purified 109P1D4 protein molecule will be substantially free of other proteins or molecules that impair the binding of 109P1 D4 to antibody, T cell or other ligand. The nature and degree of isolation and purification will depend on the intended use. Embodiments of a 109P1 D4 related proteins include purified 109P1D4-related proteins and functional, soluble 109P1D4-related proteins. In one embodiment, a functional, soluble 109P1 D4 protein or fragment thereof retains the ability to be bound by antibody, T cell or WO 2004/098515 PCT/US2004/013568 35 other ligand. The invention also provides 109P1 D4 proteins comprising biologically active fragments of a 109P1 D4 amino acid sequence shown in Figure 2 or Figure 3. Such proteins exhibit properties of the starting 109PI D4 protein, such as the ability to elicit the generation of antibodies that specifically bind an epitope associated with the starting 109P1 D4 protein; to be bound by such antibodies; to elicit the activation of HTL or CTL; and/or, to be recognized by HTL or CTL that also specifically bind to the starting protein. 109P1 D4-related polypeptides that contain particularly interesting structures can be predicted and/or identified using various analytical techniques well known in the art, including, for example, the methods of Chou-Fasman, Garnier-Robson, Kyte Doolittle, Eisenberg, Karplus-Schultz or Jameson-Wolf analysis, or based on immunogenicity. Fragments that contain such structures are particularly useful in generating subunit-specific anti-109PI D4 antibodies or T cells or in identifying cellular factors that bind to 109P1D4. For example, hydrophilicity profiles can be generated, and immunogenic peptide fragments identified, using the method of Hopp, T.P. and Woods, K.R., 1981, Proc. Natl. Acad. Sci. U.S.A. 78:3824-3828. Hydropathicity profiles can be generated, and immunogenic peptide fragments identified, using the method of Kyte, J. and Doolittle, R.F., 1982, J. Mol. Biol. 157:105-132. Percent (%) Accessible Residues profiles can be generated, and immunogenic peptide fragments identified, using the method of Janin J., 1979, Nature 277:491-492. Average Flexibility profiles can be generated, and immunogenic peptide fragments identified, using the method of Bhaskaran R., Ponnuswamy P.K., 1988, Int. J. Pept. Protein Res. 32:242-255. Beta-turn profiles can be generated, and immunogenic peptide fragments identified, using the method of Deleage, G., Roux B., 1987, Protein Engineering 1:289-294. CTL epitopes can be determined using specific algorithms to identify peptides within a 109P1D4 protein that are capable of optimally binding to specified HLA alleles (e.g., by using the SYFPEITHI site at World Wide Web URL syfpeithi.bmi heidelberg.com/; the listings in Table IV(A)-(E); Epimatrix TM and Epimer

TM

, Brown University, URL (brown.edu/ResearchTB HIVLab/epimatrixlepimatrix.html); and BIMAS, URL bimas.dcrtnih.gov/). Illustrating this, peptide epitopes from 109P1D4 that are presented in the context of human MHC Class I molecules, e.g., HLA-A1, A2, A3, Al1, A24, B7 and B35 were predicted (see, e.g., Tables VIII-XXI, XXII-XLIX). Specifically, the complete amino acid sequence of the 109P1D4 protein and relevant portions of other variants, i.e., for HLA Class I predictions 9 flanking residues on either side of a point mutation or exon juction, and for HLA Class Il predictions 14 flanking residues on either side of a point mutation or exon junction corresponding to that variant, were entered into the HLA Peptide Motif Search algorithm found in the Bioinformatics and Molecular Analysis Section (BIMAS) web site listed above; in addition to the site SYFPEITHI, at URL syfpeithibmi heidelberg.com/. The HLA peptide motif search algorithm was developed by Dr. Ken Parker based on binding of specific peptide sequences in the groove of HLA Class I molecules, in particular HLA-A2 (see, e.g., Falk et al., Nature 351: 290-6 (1991); Hunt et a., Science 255:1261-3 (1992); Parker et al., J. Immunol. 149:3580-7 (1992); Parker et al., J. Immunol. 152:163-75 (1994)). This algorithm allows location and ranking of 8-mer, 9-mer, and 10-mer peptides from a complete protein sequence for predicted binding to HLA-A2 as well as numerous other HLA Class I molecules. Many HLA class I binding peptides are 8-, 9-, 10 or 11-mers. For example, for Class I HLA-A2, the epitopes preferably contain a leucine (L) or methionine (M) at position 2 and a valine (V) or leucine (L) at the C-terminus (see, e.g., Parker et al., J. Immunol. 149:3580-7 (1992)). Selected results of 109P1D4 predicted binding peptides are shown in Tables VIII-XXI and XXII-XLIX herein. In Tables VIll XXI and XXII-XLVII, selected candidates, 9-mers and 1O-mers, for each family member are shown along with their location, the amino acid sequence of each specific peptide, and an estimated binding score. In Tables XLVI-XLIX, selected candidates, 15-mers, for each family member are shown along with their location, the amino acid sequence of each specific peptide, and an estimated binding score. The binding score corresponds to the estimated half time of dissociation of WO 2004/098515 PCT/US2004/013568 36 complexes containing the peptide at 370C at pH 6.5. Peptides with the highest binding score are predicted to be the most tightly bound to HLA Class I on the cell surface for the greatest period of time and thus represent the best immunogenic targets for T-cell recognition. Actual binding of peptides to an HLA allele can be evaluated by stabilization of HLA expression on the antigen processing defective cell line T2 (see, e.g., Xue et al., Prostate 30:73-8 (1997) and Peshwa eta)., Prostate 36:129-38 (1998)). Immunogenicity of specific peptides can be evaluated in vitro by stimulation of CD8+ cytotoxic T lymphocytes (CTL) in the presence of antigen presenting cells such as dendritic cells. It is to be appreciated that every epitope predicted by the BIMAS site, Epimer T M and Epimatrix T M sites, or specified by the HLA class I or class ii motifs available in the art or which become part of the art such as set forth in Table IV (or determined using World Wide Web site URL syfpeithi.bmi-heidelberg.com/, or BIMAS, bimas.dcrt.nih.gov/) are to be "applied" to a 109P1D4 protein in accordance with the invention. As used in this context "applied" means that a 109P1D4 protein is evaluated, e.g., visually or by computer-based patterns finding methods, as appreciated by those of skill in the relevant art. Every subsequence of a 109P1D4 protein of 8, 9, 10, or 11 amino acid residues that bears an HLA Class I motif, or a subsequence of 9 or more amino acid residues that bear an HLA Class il motif are within the scope of the invention, IlI.B.) Expression of 109P1D4-related Proteins In an embodiment described in the examples that follow, 109P1 D4 can be conveniently expressed in cells (such as 293T cells) transfected with a commercially available expression vector such as a CMV-driven expression vector encoding 109P1D4 with a C-terminal 6XHis and MYC tag (pcDNA3.1/mycHIS, Invitrogen or Tag5, GenHunter Corporation, Nashville TN). The Tag5 vector provides an IgGK secretion signal that can be used to facilitate the production of a secreted 109P1D4 protein in transfected cells. The secreted HIS-tagged 109PID4 in the culture media can be purified, e.g., using a nickel column using standard techniques. 111I.C.) Modifications of 109P1D4-related Proteins Modifications of 109P1 D4-related proteins such as covalent modifications are included within the scope of this invention. One type of covalent modification includes reacting targeted amino acid residues of a 109P1D4 polypeptide with an organic derivatizing agent that is capable of reacting with selected side chains or the N- or C- terminal residues of a 109P1D4 protein. Another type of covalent modification of a 109P1D4 polypeptide included within the scope of this invention comprises altering the native glycosylation pattern of a protein of the invention. Another type of covalent modification of 109P1D4 comprises linking a 109P1D4 polypeptide to one of a variety of nonproteinaceous polymers, e.g., polyethylene glycol (PEG), polypropylene glycol, or polyoxyalkylenes, in the manner set forth in U.S. Patent Nos. 4,640,835; 4,496,689; 4,301,144; 4,670,417; 4,791,192 or 4,179,337. The 109P1 D4-related proteins of the present invention can also be modified to form a chimeric molecule comprising 109P1D4 fused to another, heterologous polypeptide or amino acid sequence. Such a chimeric molecule can be synthesized chemically or recombinantly. A chimeric molecule can have a protein of the invention fused to another tumor associated antigen or fragment thereof. Alternatively, a protein in accordance with the invention can comprise a fusion of fragments of a 109P1D4 sequence (amino or nucleic acid) such that a molecule is created that is not, through its length, directly homologous to the amino or nucleic acid sequences shown in Figure 2 or Figure 3. Such a chimeric molecule can comprise multiples of the same subsequence of 109P1D4. A chimeric molecule can comprise a fusion of a 109P1D4-related protein with a polyhistidine epitope tag, which provides an epitope to which immobilized nickel can selectively bind, with cytokines or with growth factors. The epitope tag is generally placed at the amino- or carboxyl- terminus of a 109P1 D4 WO 2004/098515 PCT/US2004/013568 37 protein. In an alternative embodiment, the chimeric molecule can comprise a fusion of a 109P1 D4-related protein with an immunoglobulin or a particular region of an immunoglobulin. For a bivalent form of the chimeric molecule (also referred to as an "immunoadhesin"), such a fusion could be to the Fc region of an IgG molecule. The Ig fusions preferably include the substitution of a soluble (transmembrane domain deleted or inactivated) form of a 109P1D4 polypeptide in place of at least one variable region within an Ig molecule. In a preferred embodiment, the immunoglobulin fusion includes the hinge, CH2 and CH3, or the hinge, CHI, CH2 and CH3 regions of an IgGI molecule. For the production of immunoglobulin fusions see, e.g., U.S. Patent No. 5,428,130 issued June 27, 1995. 111.D.) Uses of 109P1D4-related Proteins The proteins of the invention have a number of different specific uses. As 109P1D4 is highly expressed in prostate and other cancers, 109P1D4-related proteins are used in methods that assess the status of 109P1D4 gene products in normal versus cancerous tissues, thereby elucidating the malignant phenotype. Typically, polypeptides from specific regions of a 109P1 D4 protein are used to assess the presence of perturbations (such as deletions, insertions, point mutations etc.) in those regions (such as regions containing one or more motifs). Exemplary assays utilize antibodies or T cells targeting 109P1 D4-related proteins comprising the amino acid residues of one or more of the biological motifs contained within a 109P1 D4 polypeptide sequence in order to evaluate the characteristics of this region in normal versus cancerous tissues or to elicit an immune response to the epitope. Alternatively, 109P1 D4-related proteins that contain the amino acid residues of one or more of the biological motifs in a 109P1 D4 protein are used to screen for factors that interact with that region of 109P1D4. 109P1D4 protein fragments/subsequences are particularly useful in generating and characterizing domain-specific antibodies (e.g., antibodies recognizing an extracellular or intracellular epitope of a 109P1 D4 protein), for identifying agents or cellular factors that bind to 109P1 D4 or a particular structural domain thereof, and in various therapeutic and diagnostic contexts, including but not limited to diagnostic assays, cancer vaccines and methods of preparing such vaccines. Proteins encoded by the 109P1 D4 genes, or by analogs, homologs or fragments thereof, have a variety of uses, including but not limited to generating antibodies and in methods for identifying ligands and other agents and cellular constituents that bind to a 109P1D4 gene product. Antibodies raised against a 109Pi D4 protein or fragment thereof are useful in diagnostic and prognostic assays, and imaging methodologies in the management of human cancers characterized by expression of 109P1D4 protein, such as those listed in Table . Such antibodies can be expressed intracellularly and used in methods of treating patients with such cancers. 109P11D4-related nucleic acids or proteins are also used in generating HTL or CTL responses. Various immunological assays useful for the detection of 109P1 D4 proteins are used, including but not limited to various types of radioimmunoassays, enzyme-linked immunosorbent assays (ELISA), enzyme-linked immunofluorescent assays (ELIFA), immunocytochemical methods, and the like. Antibodies can be labeled and used as immunological imaging reagents capable of detecting 109P104-expressing cells (e.g., in radioscintigraphic imaging methods). 109P1D4 proteins are also particularly useful in generating cancer vaccines, as further described herein. IV.) 109PiD4 Antibodies Another aspect of the invention provides antibodies that bind to 109P1D4-related proteins. Preferred antibodies specifically bind to a 109P1D4-related protein and do not bind (or bind weakly) to peptides or proteins that are not 109P11D4 related proteins under physiological conditions. In this context, examples of physiological conditions include: 1) phosphate buffered saline; 2) Tris-buffered saline containing 25mM Tris and 150 mM NaCI; or normal saline (0.9% NaC); 4) animal serum WO 2004/098515 PCT/US2004/013568 38 such as human serum; or, 5) a combination of any of 1) through 4); these reactions preferably taking place at pH 7.5, alternatively in a range of pH 7.0 to 8.0, or alternatively in a range of pH 6.5 to 8.5; also, these reactions taking place at a temperature between 4"C to 37"C. For example, antibodies that bind 109P1 D4 can bind 109P1 D4-related proteins such as the homologs or analogs thereof. 109P1 D4 antibodies of the invention are particularly useful in cancer (see, e.g., Table I) diagnostic and prognostic assays, and imaging methodologies. Similarly, such antibodies are useful in the treatment, diagnosis, and/or prognosis of other cancers, to the extent 109P1 D4 is also expressed or overexpressed in these other cancers. Moreover, intracellularly expressed antibodies (e.g., single chain antibodies) are therapeutically useful in treating cancers in which the expression of 109P1D4 is involved, such as advanced or metastatic prostate cancers. The invention also provides various immunological assays useful for the detection and quantification of 109P1 D4 and mutant 109P1D4-related proteins. Such assays can comprise one or more 109P1D4 antibodies capable of recognizing and binding a 109P1D4-related protein, as appropriate. These assays are performed within various immunological assay formats well known in the art, including but not limited to various types of radioimmunoassays, enzyme-linked immunosorbent assays (ELISA), enzyme-linked immunofluorescent assays (ELIFA), and the like. Immunological non-antibody assays of the invention also comprise T cell immunogenicity assays (inhibitory or stimulatory) as well as major histocompatibility complex (MHC) binding assays. In addition, immunological imaging methods capable of detecting prostate cancer and other cancers expressing 109P1 D4 are also provided by the invention, including but not limited to radioscintigraphic imaging methods using labeled 109P1D4 antibodies. Such assays are clinically useful in the detection, monitoring, and prognosis of 109P1D4 expressing cancers such as prostate cancer. 109P1D4 antibodies are also used in methods for purifying a 109P1D4-related protein and for isolating 109P1D4 homologues and related molecules. For example, a method of purifying a 109P1 D4-related protein comprises incubating a 109P1D4 antibody, which has been coupled to a solid matrix, with a lysate or other solution containing a 109P1 D4-related protein under conditions that permit the 109P1 D4 antibody to bind to the 109P1 D4-related protein; washing the solid matrix to eliminate impurities; and eluting the 109P1D4-related protein from the coupled antibody. Other uses of 109P1D4 antibodies in accordance with the invention include generating anti-idiotypic antibodies that mimic a 109P1D4 protein. Various methods for the preparation of antibodies are well known in the art For example, antibodies can be prepared by immunizing a suitable mammalian host using a 109P1 D4-related protein, peptide, or fragment, in isolated or immunoconjugated form (Antibodies: A Laboratory Manual, CSH Press, Eds., Harlow, and Lane (1988); Harlow, Antibodies, Cold Spring Harbor Press, NY (1989)). In addition, fusion proteins of 109P1D4 can also be used, such as a 109P1D4 GST-fusion protein. In a particular embodiment, a GST fusion protein comprising all or most of the amino acid sequence of Figure 2 or Figure 3 is produced, then used as an immunogen to generate appropriate antibodies, In another embodiment, a 109P1D4-related protein is synthesized and used as an immunogen, In addition, naked DNA immunization techniques known in the art are used (with or without purified 109P1 D4-related protein or 109P1D4 expressing cells) to generate an immune response to the encoded immunogen (for review, see Donnelly et al., 1997, Ann. Rev. Immunol. 15: 617-648). The amino acid sequence of a 109P1 D4 protein as shown in Figure 2 or Figure 3 can be analyzed to select specific regions of the 109P1 D4 protein for generating antibodies. For example, hydrophobicity and hydrophilicity analyses of a 109P1 D4 amino acid sequence are used to identify hydrophilic regions in the 109P1D4 structure. Regions of a 109P1D4 protein that show immunogenic structure, as well as other regions and domains, can readily be identified using various other methods known in the art, such as Chou-Fasman, Garnier-Robson, Kyte-Doolittle, Eisenberg, Karplus-Schultz or Jameson-Wolf analysis. Hydrophilicity WO 2004/098515 PCT/US2004/013568 39 profiles can be generated using the method of Hopp, T.P. and Woods, K.R., 1981, Proc. Nati. Acad. Sci. U.S.A. 78:3824 3828. Hydropathicity profiles can be generated using the method of Kyte, J. and Doolittle, R.F., 1982, J. Mol. Biol. 157:105 132. Percent (%) Accessible Residues profiles can be generated using the method of Janin J., 1979, Nature 277:491-492. Average Flexibility profiles can be generated using the method of Bhaskaran R., Ponnuswamy P.K., 1988, Int. J. Pept. Protein Res. 32:242-255. Beta-turn profiles can be generated using the method of Deleage, G., Roux B., 1987, Protein Engineering 1:289-294. Thus, each region identified by any of these programs or methods is within the scope of the present invention. Methods for the generation of 109P1 D4 antibodies are further illustrated by way of the examples provided herein. Methods for preparing a protein or polypeptide for use as an immunogen are well known in the art. Also well known in the art are methods for preparing immunogenic conjugates of a protein with a carrier, such as BSA, KLH or other carrier protein. In some circumstances, direct conjugation using, for example, carbodiimide reagents are used; in other instances linking reagents such as those supplied by Pierce Chemical Co., Rockford, IL, are effective. Administration of a 109P1D4 immunogen is often conducted by injection over a suitable time period and with use of a suitable adjuvant, as is understood in the art. During the immunization schedule, titers of antibodies can be taken to determine adequacy of antibody formation. 109P1 D4 monoclonal antibodies can be produced by various means well known in the art. For example, immortalized cell lines that secrete a desired monoclonal antibody are prepared using the standard hybridoma technology of Kohler and Milstein or modifications that immortalize antibody-producing B cells, as is generally known. Immortalized cell lines that secrete the desired antibodies are screened by immunoassay in which the antigen is a 109P1D4-related protein. When the appropriate immortalized cell culture is identified, the cells can be expanded and antibodies produced either from in vitro cultures or from ascites fluid. The antibodies or fragments of the invention can also be produced, by recombinant means. Regions that bind specifically to the desired regions of a 109P1 D4 protein can also be produced in the context of chimeric or complementarity determining region (CDR) grafted antibodies of multiple species origin, Humanized or human 109P1 D4 antibodies can also be produced, and are preferred for use in therapeutic contexts. Methods for humanizing murine and other non-human antibodies, by substituting one or more of the non-human antibody CDRs for corresponding human antibody sequences, are well known (see for example, Jones et al., 1986, Nature 321: 522-525; Riechmann et al., 1988, Nature 332: 323-327; Verhoeyen et al., 1988, Science 239: 1534-1536). See also, Carter et al., 1993, Proc. Natl. Acad. Sci. USA 89: 4285 and Sims et a., 1993, J. Immunol. 151: 2296. Methods for producing fully human monoclonal antibodies include phage display and transgenic methods (for review, see Vaughan et al., 1998, Nature Biotechnology 16: 535-539). Fully human 109P1D4 monoclonal antibodies can be generated using cloning technologies employing large human Ig gene combinatorial libraries (i.e., phage display) (Griffiths and Hoogenboom, Building an in vitro immune system: human antibodies from phage display libraries. In: Protein Engineering of Antibody Molecules for Prophylactic and Therapeutic Applications in Man, Clark, M. (Ed.), Nottingham Academic, pp 45-64 (1993); Burton and Barbas, Human Antibodies from combinatorial libraries. jd., pp 65-82). Fully human 109P1D4 monoclonal antibodies can also be produced using transgenic mice engineered to contain human immunoglobulin gene loci as described in PCT Patent Application W098/24893, Kucherlapati and Jakobovits et al., published December 3, 1997 (see also, Jakobovits, 1998, Exp. Opin. Invest. Drugs 7(4): 607-614; U.S. patents 6,162,963 issued 19 December 2000; 6,150,584 issued 12 November 2000; and, 6,114598 issued 5 September 2000). This method avoids the in vitro manipulation required with phage display technology and efficiently produces high affinity authentic human antibodies. Reactivity of 109P1 D4 antibodies with a 109P1 D4-related protein can be established by a number of well known means, including Western blot, immunoprecipitation, ELISA, and FACS analyses using, as appropriate, 109P1 D4-related proteins, 109P1 D4-expressing cells or extracts thereof. A 109P1 D4 antibody or fragment thereof can be labeled with a detectable marker or conjugated to a second molecule. Suitable detectable markers include, but are not limited to, a WO 2004/098515 PCT/US2004/013568 40 radioisotope, a fluorescent compound, a bioluminescent compound, chemiluminescent compound, a metal chelator or an enzyme. Further, bi-specific antibodies specific for two or more 109P1 D4 epitopes are generated using methods generally known in the art. Homodimeric antibodies can also be generated by cross-linking techniques known in the art (e.g., Wolff et a., Cancer Res. 53: 2560-2565). V.) 109P1D4 Cellular Immune Responses The mechanism by which T cells recognize antigens has been delineated. Efficacious peptide epitope vaccine compositions of the invention induce a therapeutic or prophylactic immune responses in very broad segments of the world wide population. For an understanding of the value and efficacy of compositions of the invention that induce cellular immune responses, a brief review of immunology-related technology is provided. A complex of an HLA molecule and a peptidic antigen acts as the ligand recognized by HLA-restricted T cells (Buus, S. et al., Cell 47:1071, 1986; Babbitt, B. P. et a., Nature 317:359, 1985; Townsend, A. and Bodmer, H., Annu. Rev. /mmunol. 7:601, 1989; Germain, R. N., Annu. Rev. Immunol 11:403,1993). Through the study of single amino acid substituted antigen analogs and the sequencing of endogenously bound, naturally processed peptides, critical residues that correspond to motifs required for specific binding to HLA antigen molecules have been identified and are set forth in Table IV (see also, e.g., Southwood, et al., J. Immunol. 160:3363, 1998; Rammensee, et a., Immunogenetics 41:178, 1995; Rammensee et al, SYFPEITHI, access via World Wide Web at URL (134.2.96.221/scripts.hlaserver.dllhome.htm); Sette, A. and Sidney, J. Curr. Opin. Immunol. 10:478,1998; Engelhard, V. H., Curr. Opin. Immunol. 6:13, 1994; Sette, A. and Grey, H. M., Curr. OpIn. Immune. 4:79, 1992; Sinigaglia, F. and Hammer, J. Curr. Biol. 6:52, 1994; Ruppert et a., Cell 74:929-937, 1993; Kondo et a., J. Immunol. 155:4307-4312, 1995; Sidney et al., J. Immunol 157:3480-3490, 1996; Sidney et a., Human Immune. 45:79-93, 1996; Sette, A. and Sidney, J. Immunogenetics 1999 Nov; 50(3-4):201-12, Review). Furthermore, x-ray crystallographic analyses of HLA-peptide complexes have revealed pockets within the peptide binding cleft/groove of HLA molecules which accommodate, in an allele-specific mode, residues borne by peptide ligands; these residues in turn determine the HLA binding capacity of the peptides in which they are present. (See, e.g., Madden, D.R. Annu. Rev. Immune. 13:587, 1995; Smith, et a., /mmunity 4:203, 1996; Fremont et al, Immunity 8:305, 1998; Stern et al., Structure 2:245, 1994; Jones, E.Y. Curr. Opin. Immunol. 9:75, 1997; Brown, J. H. et a., Nature 364:33, 1993; Guo, H. C. et a., Proc. Nat. Acad. Sci. USA 90:8053, 1993; Guo, H. C. et aL., Nature 360:364, 1992; Silver, M. L. et a., Nature 360:367, 1992; Matsumura, M. et a., Science 257:927, 1992; Madden et a., Cell70:1035, 1992; Fremont, D. H. et a., Science 257:919, 1992; Saper, M. A., Bjorkman, P. J. and Wiley, D. C., J. Mo. Biol. 219:277,1991.) Accordingly, the definition of class I and class Il allele-specific HLA binding motifs, or class I or class 11 supermotifs allows identification of regions within a protein that are correlated with binding to particular HLA antigen(s). Thus, by a process of HLA motif identification, candidates for epitope-based vaccines have been identified; such candidates can be further evaluated by HLA-peptide binding assays to determine binding affinity and/or the time period of association of the epitope and its corresponding HLA molecule. Additional confirmatory work can be performed to select, amongst these vaccine candidates, epitopes with preferred characteristics in terms of population coverage, and/or immunogenicity. Various strategies can be utilized to evaluate cellular immunogenicity, including: 1) Evaluation of primary T cell cultures from normal individuals (see, e.g., Wentworth, P. A. et a., Mol. Immunol. 32:603, 1995; Cells, E. et a., Proc. Natl. Aced. Sci. USA 91:2105, 1994; Tsai, V. et al., J. Immunol. 158:1796, 1997; Kawashima, I. et a., Human lmmunol. 59:1, 1998). This procedure involves the stimulation of peripheral blood lymphocytes (PBL) from normal subjects with a test peptide in the presence of antigen presenting cells in vitro over a period of several WO 2004/098515 PCT/US2004/013568 41 weeks. T cells specific for the peptide become activated during this time and are detected using, e.g., a lymphokine- or 51Cr-release assay involving peptide sensitized target cells. 2) Immunization of HLA transgenic mice (see, e.g., Wentworth, P. A. et al., J. Immunol. 2697, 1996; Wentworth, P. A. et a., int. Immunol. 8:651, 1996; Alexander, J. et al., J. Immunol. 159:4753, 1997). For example, in such methods peptides in incomplete Freund's adjuvant are administered subcutaneously to HLA transgenic mice. Several weeks following immunization, splenocytes are removed and cultured in vitro in the presence of test peptide for approximately one week. Peptide-specific T cells are detected using, e.g., a 51 Cr-release assay involving peptide sensitized target cells and target cells expressing endogenously generated antigen. 3) Demonstration of recall T cell responses from immune individuals who have been either effectively vaccinated and/or from chronically ill patients (see, e.g., Rehermann, B. et a., J. Exp. Med. 181:1047, 1995; Doolan, D. L. et al., Immunity 7:97, 1997; Bertoni, R. et al., J. Clin. Invest. 100:503, 1997; Threlkeld, S. C. et al., J. Immunol. 159:1648, 1997; Diepolder, H. M. et al., J. Virol. 71:6011, 1997). Accordingly, recall responses are detected by culturing PBL from subjects that have been exposed to the antigen due to disease and thus have generated an immune response "naturally", or from patients who were vaccinated against the antigen. PBL from subjects are cultured in vitro for 1-2 weeks in the presence of test peptide plus antigen presenting cells (APC) to allow activation of "memory" T cells, as compared to "naive" T cells. At the end of the culture period, T cell activity is detected using assays including 51 Cr release involving peptide-sensitized targets, T cell proliferation, or lymphokine release. VI.) 109P1 D4 Transgenic Animals Nucleic acids that encode a 109P1D4-related protein can also be used to generate either transgenic animals or "knock out" animals that, in turn, are useful in the development and screening of therapeutically useful reagents. In accordance with established techniques, cDNA encoding 109P1 D4 can be used to clone genomic DNA that encodes 109P1D4. The cloned genomic sequences can then be used to generate transgenic animals containing cells that express DNA that encode 109P1 D4. Methods for generating transgenic animals, particularly animals such as mice or rats, have become conventional in the art and are described, for example, in U.S. Patent Nos. 4,736,866 issued 12 April 1988, and 4,870,009 issued 26 September 1989. Typically, particular cells would be targeted for 109P1D4 transgene incorporation with tissue-specific enhancers. Transgenic animals that include a copy of a transgene encoding 1 09P1 D4 can be used to examine the effect of increased expression of DNA that encodes 109P1 D4. Such animals can be used as tester animals for reagents thought to confer protection from, for example, pathological conditions associated with its overexpression. In accordance with this aspect of the invention, an animal is treated with a reagent and a reduced incidence of a pathological condition, compared to untreated animals that bear the transgene, would indicate a potential therapeutic intervention for the pathological condition. Alternatively, non-human homologues of 109P1D4 can be used to construct a 109P1D4 "knock out" animal that has a defective or altered gene encoding 109P1 D4 as a result of homologous recombination between the endogenous gene encoding 109P1D4 and altered genomic DNA encoding 109P1D4 introduced into an embryonic cell of the animal. For example, cDNA that encodes 109P1 D4 can be used to clone genomic DNA encoding 109P1 D4 in accordance with established techniques. A portion of the genomic DNA encoding 109P1D4 can be deleted or replaced with another gene, such as a gene encoding a selectable marker that can be used to monitor integration. Typically, several kilobases of unaltered flanking DNA (both at the 5' and 3' ends) are included in the vector (see, e.g., Thomas and Capecchi, Cell 51:503 (1987) for a description of homologous recombination vectors). The vector is introduced into an embryonic stem cell line (e.g., by electroporation) and cells in which the introduced DNA has homologously recombined with the endogenous DNA WO 2004/098515 PCT/US2004/013568 42 are selected (see, e.g., Li et al., Cll, 69915 (1992)). The selected cells are then injected into a blastocyst of an animal (e.g., a mouse or rat) to form aggregation chimeras (see, e.g., Bradley, in Teratocarcinomas and Embryonic Stem Cells: A Practical Approach, E. J. Robertson, ed. (IRL, Oxford, 1987), pp. 113-152). A chimeric embryo can then be implanted into a suitable pseudopregnant female foster animal, and the embryo brought to term to create a "knock out" animal. Progeny harboring the homologously recombined DNA in their germ cells can be identified by standard techniques and used to breed animals in which all cells of the animal contain the homologously recombined DNA. Knock out animals can be characterized, for example, for their ability to defend against certain pathological conditions or for their development of pathological conditions due to absence of a 109P1 D4 polypeptide. VI.) Methods for the Detection of 109P1D4 Another aspect of the present invention relates to methods for detecting 109P1D4 polynucleotides and 109P1D4 related proteins, as well as methods for identifying a cell that expresses 109P1 D4. The expression profile of 109P1 D4 makes it a diagnostic marker for metastasized disease. Accordingly, the status of 109P1D4 gene products provides information useful for predicting a variety of factors including susceptibility to advanced stage disease, rate of progression, and/or tumor aggressiveness. As discussed in detail herein, the status of 109P1D4 gene products in patient samples can be analyzed by a variety protocols that are well known in the art including immunohistochemical analysis, the variety of Northern blotting techniques including in situ hybridization, RT-PCR analysis (for example on laser capture micro-dissected samples), Western blot analysis and tissue array analysis. More particularly, the invention provides assays for the detection of 109P1 D4 polynucleotides in a biological sample, such as serum, bone, prostate, and other tissues, urine, semen, cell preparations, and the like. Detectable 109P1D4 polynucleotides include, for example, a 109P1 D4 gene or fragment thereof, 109P1D4 mRNA, alternative splice variant 109P1D4 mRNAs, and recombinant DNA or RNA molecules that contain a 109P1D4 polynucleotide. A number of methods for amplifying and/or detecting the presence of 109P1D4 polynucleotides are well known in the art and can be employed in the practice of this aspect of the invention. In one embodiment, a method for detecting a 109P1 D4 mRNA in a biological sample comprises producing cDNA from the sample by reverse transcription using at least one primer; amplifying the cDNA so produced using a 109P1 D4 polynucleotides as sense and antisense primers to amplify I 09P1 D4 cDNAs therein; and detecting the presence of the amplified 109P1D4 cDNA. Optionally, the sequence of the amplified 109P1D4 cDNA can be determined. In another embodiment, a method of detecting a 109Pi D4 gene in a biological sample comprises first isolating genomic DNA from the sample; amplifying the isolated genomic DNA using 109P1 D4 polynucleotides as sense and antisense primers; and detecting the presence of the amplified 109P1 D4 gene. Any number of appropriate sense and antisense probe combinations can be designed from a 109P1D4 nucleotide sequence (see, e.g., Figure 2) and used for this purpose. The invention also provides assays for detecting the presence of a 109P1 D4 protein in a tissue or other biological sample such as serum, semen, bone, prostate, urine, cell preparations, and the like. Methods for detecting a 109P1 D4-related protein are also well known and include, for example, immunoprecipitation, immunohistochemical analysis, Western blot analysis, molecular binding assays, ELISA, ELIFA and the like. For example, a method of detecting the presence of a 109P1 D4-related protein in a biological sample comprises first contacting the sample with a 109P1D4 antibody, a 109P1 D4-reactive fragment thereof, or a recombinant protein containing an antigen-binding region of a 109P1D4 antibody; and then detecting the binding of 109P1D4-related protein in the sample. Methods for identifying a cell that expresses 109P1 D4 are also within the scope of the invention. In one embodiment, WO 2004/098515 PCT/US2004/013568 43 an assay for identifying a cell that expresses a 109P1D4 gene comprises detecting the presence of 109P1D4 mRNA in the cell. Methods for the detection of particular mRNAs in cells are well known and include, for example, hybridization assays using complementary DNA probes (such as in situ hybridization using labeled 109P1 D4 riboprobes, Northern blot and related techniques) and various nucleic acid amplification assays (such as RT-PCR using complementary primers specific for 109P1 D4, and other amplification type detection methods, such as, for example, branched DNA, SISBA, TMA and the like). Alternatively, an assay for identifying a cell that expresses a 109P1 D4 gene comprises detecting the presence of 109P1 D4-related protein in the cell or secreted by the cell. Various methods for the detection of proteins are well known in the art and are employed for the detection of 109P1 D4-related proteins and cells that express 109P1 D4-related proteins. 109P1 D4 expression analysis is also useful as a tool for identifying and evaluating agents that modulate 109P1 D4 gene expression. For example, 109P1 D4 expression is significantly upregulated in prostate cancer, and is expressed in cancers of the tissues listed in Table 1. Identification of a molecule or biological agent that inhibits 109P1 D4 expression or over expression in cancer cells is of therapeutic value. For example, such an agent can be identified by using a screen that quantifies 109P1D4 expression by RT-PCR, nucleic acid hybridization or antibody binding. Vill.) Methods for Monitoring the Status of 109PiD4-related Genes and Their Products Oncogenesis is known to be a multistep process where cellular growth becomes progressively dysregulated and cells progress from a normal physiological state to precancerous and then cancerous states (see, e.g., Alers et aL., Lab Invest. 77(5): 437-438 (1997) and Isaacs et al., Cancer Surv. 23: 19-32 (1995)). In this context, examining a biological sample for evidence of dysregulated cell growth (such as aberrant 109P1 D4 expression in cancers) allows for early detection of such aberrant physiology, before a pathologic state such as cancer has progressed to a stage that therapeutic options are more limited and or the prognosis is worse. In such examinations, the status of 109P1 D4 in a biological sample of interest can be compared, for example, to the status of 109P1 D4 in a corresponding normal sample (e.g. a sample from that individual or alternatively another individual that is not affected by a pathology). An alteration in the status of 109P1D4 in the biological sample (as compared to the normal sample) provides evidence of dysregulated cellular growth. In addition to using a biological sample that is not affected by a pathology as a normal sample, one can also use a predetermined normative value such as a predetermined normal level of mRNA expression (see, e.g., Grever et al., J. Comp. Neurol. 1996 Dec 9; 376(2): 306-14 and U.S. Patent No. 5,837,501) to compare 109P1D4 status in a sample. The term "status" in this context is used according to its art accepted meaning and refers to the condition or state of a gene and its products. Typically, skilled artisans use a number of parameters to evaluate the condition or state of a gene and its products. These include, but are not limited to the location of expressed gene products (including the location of 109P1D4 expressing cells) as well as the level, and biological activity of expressed gene products (such as 109P1 D4 mRNA, polynucleotides and polypeptides). Typically, an alteration in the status of 109P1 D4 comprises a change in the location of 109P1D4 and/or 109P1D4 expressing cells and/or an increase in 109P1D4 mRNA and/or protein expression. 109P1 D4 status in a sample can be analyzed by a number of means well known in the art, including without limitation, immunohistochemical analysis, in situ hybridization, RT-PCR analysis on laser capture micro-dissected samples, Western blot analysis, and tissue array analysis. Typical protocols for evaluating the status of a 109P1 D4 gene and gene products are found, for example in Ausubel et al. eds., 1995, Current Protocols In Molecular Biology, Units 2 (Northern Blotting), 4 (Southern Blotting), 15 (Immunoblotting) and 18 (PCR Analysis). Thus, the status of 109P1D4 in a biological sample is evaluated by various methods utilized by skilled artisans including, but not limited to genomic Southern analysis (to examine, for example perturbations in a 109P1D4 gene), Northern analysis and/or PCR analysis of 109P1D4 mRNA (to examine, for example alterations in the polynucleotide sequences or expression levels of 109P1D4 mRNAs), and, Western and/or WO 2004/098515 PCT/US2004/013568 44 immunohistochemical analysis (to examine, for example alterations in polypeptide sequences, alterations in polypeptide localization within a sample, alterations in expression levels of 109P1 D4 proteins and/or associations of 109P1 D4 proteins with polypeptide binding partners). Detectable 109P1 D4 polynucleotides include, for example, a 109P1D4 gene or fragment thereof, 109P1 D4 mRNA, alternative splice variants, 109P1D4 mRNAs, and recombinant DNA or RNA molecules containing a 109P1 D4 polynucleotde. The expression profile of I 09P1 D4 makes it a diagnostic marker for local and/or metastasized disease, and provides information on the growth or oncogenic potential of a biological sample. In particular, the status of 109P1D4 provides information useful for predicting susceptibility to particular disease stages, progression, and/or tumor aggressiveness. The invention provides methods and assays for determining 109P1 D4 status and diagnosing cancers that express 109P1 D4, such as cancers of the tissues listed in Table i. For example, because 109P1 D4 mRNA is so highly expressed in prostate and other cancers relative to normal prostate tissue, assays that evaluate the levels of 109P1D4 mRNA transcripts or proteins in a biological sample can be used to diagnose a disease associated with 109P1D4 dysregulation, and can provide prognostic information useful in defining appropriate therapeutic options. The expression status of 109P1 D4 provides information including the presence, stage and location of dysplastic, precancerous and cancerous cells, predicting susceptibility to various stages of disease, and/or for gauging tumor aggressiveness. Moreover, the expression profile makes it useful as an imaging reagent for metastasized disease. Consequently, an aspect of the invention is directed to the various molecular prognostic and diagnostic methods for examining the status of 109P1 D4 in biological samples such as those from individuals suffering from, or suspected of suffering from a pathology characterized by dysregulated cellular growth, such as cancer. As described above, the status of 109P1D4 in a biological sample can be examined by a number of well-known procedures in the art. For example, the status of 109P1 D4 in a biological sample taken from a specific location in the body can be examined by evaluating the sample for the presence or absence of 109P1 D4 expressing cells (e.g. those that express 109PI1D4 mRNAs or proteins). This examination can provide evidence of dysregulated cellular growth, for example, when 109P1D4-expressing cells are found in a biological sample that does not normally contain such cells (such as a lymph node), because such alterations in the status of 109P1 D4 in a biological sample are often associated with dysregulated cellular growth. Specifically, one indicator of dysregulated cellular growth is the metastases of cancer cells from an organ of origin (such as the prostate) to a different area of the body (such as a lymph node). In this context, evidence of dysregulated cellular growth is important for example because occult lymph node metastases can be detected in a substantial proportion of patients with prostate cancer, and such metastases are associated with known predictors of disease progression (see, e.g., Murphy et aL, Prostate 42(4): 315-317 (2000);Su et aL., Semin. Surg. Oncol. 18(1): 17-28 (2000) and Freeman et aL, J Urol 1995 Aug 154(2 Pt 1):474-8). In one aspect, the invention provides methods for monitoring 109P1 D4 gene products by determining the status of 109P1 D4 gene products expressed by cells from an individual suspected of having a disease associated with dysregulated cell growth (such as hyperplasia or cancer) and then comparing the status so determined to the status of 1 09P1 D4 gene products in a corresponding normal sample. The presence of aberrant 109P1D4 gene products in the test sample relative to the normal sample provides an indication of the presence of dysregulated cell growth within the cells of the individual. In another aspect, the invention provides assays useful in determining the presence of cancer in an individual, comprising detecting a significant increase in 109P1D4 mRNA or protein expression in a test cell or tissue sample relative to expression levels in the corresponding normal cell or tissue. The presence of 109PI D4 mRNA can, for example, be evaluated in tissues including but not limited to those listed in Table I. The presence of significant 109PID4 expression in any of these tissues is useful to indicate the emergence, presence and/or severity of a cancer, since the corresponding WO 2004/098515 PCT/US2004/013568 45 normal tissues do not express 109P1 D4 mRNA or express it at lower levels. In a related embodiment, 1 09P1 D4 status is determined at the protein level rather than at the nucleic acid level. For example, such a method comprises determining the level of 109P1 D4 protein expressed by cells in a test tissue sample and comparing the level so determined to the level of 109P1 D4 expressed in a corresponding normal sample. In one embodiment, the presence of 109P1D4 protein is evaluated, for example, using immunohistochemical methods. 109P1D4 antibodies or binding partners capable of detecting 109P1 D4 protein expression are used in a variety of assay formats well known in the art for this purpose. In a further embodiment, one can evaluate the status of 109P1 D4 nucleotide and amino acid sequences in a biological sample in order to identify perturbations in the structure of these molecules. These perturbations can include insertions, deletions, substitutions and the like. Such evaluations are useful because perturbations in the nucleotide and amino acid sequences are observed in a large number of proteins associated with a growth dysregulated phenotype (see, e.g., Marrogi et al., 1999, J. Cutan. Pathol. 26(8):369-378). For example, a mutation in the sequence of 109P1D4 may be indicative of the presence or promotion of a tumor. Such assays therefore have diagnostic and predictive value where a mutation in 109P1 D4 indicates a potential loss of function or increase in tumor growth. A wide variety of assays for observing perturbations in nucleotide and amino acid sequences are well known in the art. For example, the size and structure of nucleic acid or amino acid sequences of 109P1 D4 gene products are observed by the Northern, Southern, Western, PCR and DNA sequencing protocols discussed herein. In addition, other methods for observing perturbations in nucleotide and amino acid sequences such as single strand conformation polymorphism analysis are well known in the art (see, e.g., U.S. Patent Nos. 5,382,510 issued 7 September 1999, and 5,952,170 issued 17 January 1995). Additionally, one can examine the methylation status of a 109P1 D4 gene in a biological sample. Aberrant demethylation and/or hypermethylation of CpG islands in gene 5' regulatory regions frequently occurs in immortalized and transformed cells, and can result in altered expression of various genes. For example, promoter hypermethylation of the pi-class glutathione S-transferase (a protein expressed in normal prostate but not expressed in >90% of prostate carcinomas) appears to permanently silence transcription of this gene and is the most frequently detected genomic alteration in prostate carcinomas (De Marzo et aL., Am. J. Pathol. 155(6): 1985-1992 (1999)). In addition, this alteration is present in at least 70% of cases of high-grade prostatic intraepithelial neoplasia (PIN) (Brooks at al., Cancer Epidemiol. Biomarkers Prev., 1998, 7:531-536). In another example, expression of the LAGE-1 tumor specific gene (which is not expressed in normal prostate but is expressed in 25-50% of prostate cancers) is induced by deoxy-azacytidine in lymphoblastoid cells, suggesting that tumoral expression is due to demethylation (Lathe at al., Int. J. Cancer 76(6): 903-908 (1998)). A variety of assays for examining methylation status of a gene are well known in the art. For example, one can utilize, in Southern hybridization approaches, methylation-sensitive restriction enzymes that cannot cleave sequences that contain methylated CpG sites to assess the methylation status of CpG islands. In addition, MSP (methylation specific PCR) can rapidly profile the methylation status of all the CpG sites present in a CpG island of a given gene. This procedure involves initial modification of DNA by sodium bisulfite (which will convert all unmethylated cytosines to uracil) followed by amplification using primers specific for methylated versus unmethylated DNA. Protocols involving methylation interference can also be found for example in Current Protocols In Molecular Biology, Unit 12, Frederick M. Ausubel et al. eds., 1995. Gene amplification is an additional method for assessing the status of 109P1D4. Gene amplification is measured in a sample directly, for example, by conventional Southem blotting or Northern blotting to quantitate the transcription of mRNA (Thomas, 1980, Proc. Nati. Acad. Sci. USA, 77:5201-5205), dot blotting (DNA analysis), or in situ hybridization, using an appropriately labeled probe, based on the sequences provided herein. Alternatively, antibodies are employed that recognize specific duplexes, including DNA duplexes, RNA duplexes, and DNA-RNA hybrid duplexes or DNA-protein WO 2004/098515 PCT/US2004/013568 46 duplexes. The antibodies in turn are labeled and the assay carried out where the duplex is bound to a surface, so that upon the formation of duplex on the surface, the presence of antibody bound to the duplex can be detected. Biopsied tissue or peripheral blood can be conveniently assayed for the presence of cancer cells using for example, Northern, dot blot or RT-PCR analysis to detect 109P1 D4 expression. The presence of RT-PCR amplifiable 109P1 D4 mRNA provides an indication of the presence of cancer. RT-PCR assays are well known in the art. RT-PCR detection assays for tumor cells in peripheral blood are currently being evaluated for use in the diagnosis and management of a number of human solid tumors. In the prostate cancer field, these include RT-PCR assays for the detection of cells expressing PSA and PSM (Verkaik et al., 1997, Urol. Res. 25:373-384; Ghossein et al., 1995, J. Clin. Oncol. 13:1195-2000; Heston et al., 1995, Clin. Chem. 41:1687 1688). A further aspect of the invention is an assessment of the susceptibility that an individual has for developing cancer. In one embodiment a method for predicting susceptibility to cancer comprises detecting 109P1 D4 mRNA or 109P1 D4 protein in a tissue sample, its presence indicating susceptibility to cancer, wherein the degree of 109P1 D4 mRNA expression correlates to the degree of susceptibility. In a specific embodiment, the presence of 109P1 D4 in prostate or other tissue is examined, with the presence of 109P1 D4 in the sample providing an indication of prostate cancer susceptibility (or the emergence or existence of a prostate tumor). Similarly, one can evaluate the integrity 109P1 D4 nucleotide and amino acid sequences in a biological sample, in order to identify perturbations in the structure of these molecules such as insertions, deletions, substitutions and the like. The presence of one or more perturbations in 109P1 D4 gene products in the sample is an indication of cancer susceptibility (or the emergence or existence of a tumor). The invention also comprises methods for gauging tumor aggressiveness. In one embodiment, a method for gauging aggressiveness of a tumor comprises determining the level of 109P1 D4 mRNA or 109P1 D4 protein expressed by tumor cells, comparing the level so determined to the level of 1 09P1 D4 mRNA or 1 09P1 D4 protein expressed in a corresponding normal tissue taken from the same individual or a normal tissue reference sample, wherein the degree of 109P1D4 mRNA or 109P1D4 protein expression in the tumor sample relative to the normal sample indicates the degree of aggressiveness. In a specific embodiment, aggressiveness of a tumor is evaluated by determining the extent to which 109P1 D4 is expressed in the tumor cells, with higher expression levels indicating more aggressive tumors. Another embodiment is the evaluation of the integrity of 109P1 D4 nucleotide and amino acid sequences in a biological sample, in order to identify perturbations in the structure of these molecules such as insertions, deletions, substitutions and the like. The presence of one or more perturbations indicates more aggressive tumors. Another embodiment of the invention is directed to methods for observing the progression of a malignancy in an individual over time. In one embodiment, methods for observing the progression of a malignancy in an individual over time comprise determining the level of 109P1 D4 mRNA or 109P1 D4 protein expressed by cells in a sample of the tumor, comparing the level so determined to the level of 109P1 D4 mRNA or 109P1 D4 protein expressed in an equivalent tissue sample taken from the same individual at a different time, wherein the degree of 1 09P1 D4 mRNA or 1 09P1 D4 protein expression in the tumor sample over time provides information on the progression of the cancer. In a specific embodiment, the progression of a cancer is evaluated by determining 109P1 D4 expression in the tumor cells over time, where increased expression over time indicates a progression of the cancer. Also, one can evaluate the integrity 109P1D4 nucleotide and amino acid sequences in a biological sample in order to identify perturbations in the structure of these molecules such as insertions, deletions, substitutions and the like, where the presence of one or more perturbations indicates a progression of the cancer. The above diagnostic approaches can be combined with any one of a wide variety of prognostic and diagnostic protocols known in the art. For example, another embodiment of the invention is directed to methods for observing a coincidence between the expression of 109P1 D4 gene and 109P1 D4 gene products (or perturbations in 109P1 D4 gene and 109P1 D4 gene WO 2004/098515 PCT/US2004/013568 47 products) and a factor that is associated with malignancy, as a means for diagnosing and prognosticating the status of a tissue sample. A wide variety of factors associated with malignancy can be utilized, such as the expression of genes associated with malignancy (e.g. PSA, PSCA and PSM expression for prostate cancer etc.) as well as gross cytological observations (see, e.g., Bocking et al., 1984, Anal. Quant. Cytol. 6(2):74-88; Epstein, 1995, Hum. Pathol. 26(2):223-9; Thorson et al., 1998, Mod. Pathol. 11 (6):543-51; Baisden et al., 1999, Am. J. Surg. Pathol. 23(8):918-24). Methods for observing a coincidence between the expression of 109P1 D4 gene and I 09P1 D4 gene products (or perturbations in 109P1 D4 gene and 109P1 D4 gene products) and another factor that is associated with malignancy are useful, for example, because the presence of a set of specific factors that coincide with disease provides information crucial for diagnosing and prognosticating the status of a tissue sample. In one embodiment, methods for observing a coincidence between the expression of 109P1 D4 gene and 109P1 D4 gene products (or perturbations in 109P1 D4 gene and 109P1 D4 gene products) and another factor associated with malignancy entails detecting the overexpression of 109P1 D4 mRNA or protein in a tissue sample, detecting the overexpression of PSA mRNA or protein in a tissue sample (or PSCA or PSM expression), and observing a coincidence of 109P1 D4 mRNA or protein and PSA mRNA or protein overexpression (or PSCA or PSM expression). In a specific embodiment, the expression of 109P1 D4 and PSA mRNA in prostate tissue is examined, where the coincidence of 109P1 D4 and PSA mRNA overexpression in the sample indicates the existence of prostate cancer, prostate cancer susceptibility or the emergence or status of a prostate tumor. Methods for detecting and quantifying the expression of 109P1D4 mRNA or protein are described herein, and standard nucleic acid and protein detection and quantification technologies are well known in the art. Standard methods for the detection and quantification of 109P1 D4 mRNA include in situ hybridization using labeled 109P1 D4 riboprobes, Northern blot and related techniques using 109P1 D4 polynucleotide probes, RT-PCR analysis using primers specific for 1 09P1 D4, and other amplification type detection methods, such as, for example, branched DNA, SISBA, TMA and the like. In a specific embodiment, semi quantitative RT-PCR is used to detect and quantify 109P1 D4 mRNA expression. Any number of primers capable of amplifying 109P1 D4 can be used for this purpose, including but not limited to the various primer sets specifically described herein. In a specific embodiment, polyclonal or monoclonal antibodies specifically reactive with the wild-type 109P1 D4 protein can be used in an immunohistochemical assay of biopsied tissue. IX.) Identification of Molecules That Interact With 109P1D4 The 109P1D4 protein and nucleic acid sequences disclosed herein allow a skilled artisan to identify proteins, small molecules and other agents that interact with 109P1 D4, as well as pathways activated by 109P1 D4 via any one of a variety of art accepted protocols. For example, one can utilize one of the so-called interaction trap systems (also referred to as the "two-hybrid assay"). In such systems, molecules interact and reconstitute a transcription factor which directs expression of a reporter gene, whereupon the expression of the reporter gene is assayed. Other systems identify protein-protein interactions in vivo through reconstitution of a eukaryotic transcriptional activator, see, e.g., U.S. Patent Nos. 5,955,280 issued 21 September 1999, 5,925,523 issued 20 July 1999, 5,846,722 issued 8 December 1998 and 6,004,746 issued 21 December 1999. Algorithms are also available in the art for genome-based predictions of protein function (see, e.g., Marcotte, et al., Nature 402: 4 November 1999, 83-86). Alternatively one can screen peptide libraries to identify molecules that interact with 109P1 D4 protein sequences. In such methods, peptides that bind to 109P1 D4 are identified by screening libraries that encode a random or controlled collection of amino acids. Peptides encoded by the libraries are expressed as fusion proteins of bacteriophage coat proteins, the bacteriophage particles are then screened against the 109P1 D4 protein(s). Accordingly, peptides having a wide variety of uses, such as therapeutic, prognostic or diagnostic reagents, are thus identified without any prior information on the structure of the expected ligand or receptor molecule. Typical peptide WO 2004/098515 PCT/US2004/013568 48 libraries and screening methods that can be used to identify molecules that interact with 109P1 D4 protein sequences are disclosed for example in U.S. Patent Nos. 5,723,286 issued 3 March 1998 and 5,733,731 issued 31 March 1998. Alternatively, cell lines that express 109P1 D4 are used to identify protein-protein interactions mediated by 109P1D4. Such interactions can be examined using immunoprecipitation techniques (see, e.g., Hamilton B.J., et al. Biochem. Biophys. Res. Commun. 1999, 261:646-51). 109P1D4 protein can be immunoprecipitated from 109P1D4 expressing cell lines using anti-109P1D4 antibodies. Alternatively, antibodies against His-tag can be used in a cell line engineered to express fusions of 109P1D4 and a His-tag (vectors mentioned above). The immunoprecipitated complex can be examined for protein association by procedures such as Western blotting, 3 S-methionine labeling of proteins, protein microsequencing, silver staining and two-dimensional gel electrophoresis. Small molecules and ligands that interact with 109P1D4 can be identified through related embodiments of such screening assays. For example, small molecules can be identified that interfere with protein function, including molecules that interfere with 109P1 D4's ability to mediate phosphorylation and de-phosphorylation, interaction with DNA or RNA molecules as an indication of regulation of cell cycles, second messenger signaling or tumorigenesis. Similarly, small molecules that modulate 109P1 D4-related ion channel, protein pump, or cell communication functions are identified and used to treat patients that have a cancer that expresses 109P1D4 (see, e.g., Hille, B., Ionic Channels of Excitable Membranes 2nd Ed., Sinauer Assoc., Sunderland, MA, 1992). Moreover, ligands that regulate 109P1 D4 function can be identified based on their ability to bind 109P1 D4 and activate a reporter construct. Typical methods are discussed for example in U.S. Patent No. 5,928,868 issued 27 July 1999, and include methods for forming hybrid ligands in which at least one ligand is a small molecule. In an illustrative embodiment, cells engineered to express a fusion protein of 109P1 D4 and a DNA-binding protein are used to co-express a fusion protein of a hybrid ligand/small molecule and a cDNA library transcriptional activator protein. The cells further contain a reporter gene, the expression of which is conditioned on the proximity of the first and second fusion proteins to each other, an event that occurs only if the hybrid ligand binds to target sites on both hybrid proteins. Those cells that express the reporter gene are selected and the unknown small molecule or the unknown ligand is identified. This method provides a means of identifying modulators, which activate or inhibit 1 09P1 D4. An embodiment of this invention comprises a method of screening for a molecule that interacts with a 109P1 D4 amino acid sequence shown in Figure 2 or Figure 3, comprising the steps of contacting a population of molecules with a 109P1D4 amino acid sequence, allowing the population of molecules and the 109P1D4 amino acid sequence to interact under conditions that facilitate an interaction, determining the presence of a molecule that interacts with the 109P1 D4 amino acid sequence, and then separating molecules that do not interact with the 109P1 D4 amino acid sequence from molecules that do. In a specific embodiment, the method further comprises purifying, characterizing and identifying a molecule that interacts with the 109P1 D4 amino acid sequence. The identified molecule can be used to modulate a function performed by 109P1 D4. In a preferred embodiment, the 109P1 D4 amino acid sequence is contacted with a library of peptides. X. Therapeutic Methods and Compositions The identification of 1 09P1 D4 as a protein that is normally expressed in a restricted set of tissues, but which is also expressed in cancers such as those listed in Table 1, opens a number of therapeutic approaches to the treatment of such cancers. Of note, targeted antitumor therapies have been useful even when the targeted protein is expressed on normal tissues, even vital normal organ tissues. A vital organ is one that is necessary to sustain life, such as the heart or colon. A non-vital organ is one that can be removed whereupon the individual is still able to survive. Examples of non-vital organs are ovary, breast, and prostate.

WO 2004/098515 PCT/US2004/013568 49 For example, Herceptin@ is an FDA approved pharmaceutical that has as its active ingredient an antibody which is immunoreactive with the protein variously known as HER2, HER2/neu, and erb-b-2. It is marketed by Genentech and has been a commercially successful antitumor agent. Herceptin sales reached almost $400 million in 2002. Herceptin is a treatment for HER2 positive metastatic breast cancer. However, the expression of HER2 is not limited to such tumors. The same protein is expressed in a number of normal tissues. In particular, it is known that HER2/neu is present in normal kidney and heart, thus these tissues are present in all human recipients of Herceptin. The presence of HER2/neu in normal kidney is also confirmed by Latif, Z., et al., B.J. U. International (2002) 89:5-9. As shown in this article (which evaluated whether renal cell carcinoma should be a preferred indication for anti-HER2 antibodies such as Herceptin) both protein and mRNA are produced in benign renal tissues. Notably, HER2/neu protein was strongly overexpressed in benign renal tissue. Despite the fact that HER2/neu is expressed in such vital tissues as heart and kidney, Herceptin is a very useful, FDA approved, and commercially successful drug. The effect of Herceptin on cardiac tissue, i.e., "cardiotoxicity," has merely been a side effect to treatment. When patients were treated with Herceptin alone, significant cardiotoxicity occurred in a very low percentage of patients. Of particular note, although kidney tissue is indicated to exhibit normal expression, possibly even higher expression than cardiac tissue, kidney has no appreciable Herceptin side effect whatsoever. Moreover, of the diverse array of normal tissues in which HER2 is expressed, there is very little occurrence of any side effect. Only cardiac tissue has manifested any appreciable side effect at all. A tissue such as kidney, where HER2/neu expression is especially notable, has not been the basis for any side effect. Furthermore, favorable therapeutic effects have been found for antitumor therapies that target epidermal growth factor receptor (EGFR). EGFR is also expressed in numerous normal tissues. There have been very limited side effects in normal tissues following use of anti-EGFR therapeutics. Thus, expression of a target protein in normal tissue, even vital normal tissue, does not defeat the utility of a targeting agent for the protein as a therapeutic for certain tumors in which the protein is also overexpressed. Accordingly, therapeutic approaches that inhibit the activity of a 1 09P1 D4 protein are useful for patients suffering from a cancer that expresses 109P1 D4. These therapeutic approaches generally fall into two classes. One class comprises various methods for inhibiting the binding or association of a 109P1 D4 protein with its binding partner or with other proteins. Another class comprises a variety of methods for inhibiting the transcription of a 109P1 D4 gene or translation of 109P1 D4 mRNA. X.A.) Anti-Cancer Vaccines The invention provides cancer vaccines comprising a 109P1D4-related protein or 109P1D4-related nucleic acid. In view of the expression of 109P1 D4, cancer vaccines prevent and/or treat 109P1 D4-expressing cancers with minimal or no effects on non-target tissues. The use of a tumor antigen in a vaccine that generates humoral and/or cell-mediated immune responses as anti-cancer therapy is well known in the art and has been employed in prostate cancer using human PSMA and rodent PAP immunogens (Hodge et al., 1995, Int. J. Cancer 63:231-237; Fong et al., 1997, J. Immunol. 159:3113-3117). Such methods can be readily practiced by employing a 109P1D4-related protein, or a 109P1D4-encoding nucleic acid molecule and recombinant vectors capable of expressing and presenting the 109P1 D4 immunogen (which typically comprises a number of antibody or T cell epitopes). Skilled artisans understand that a wide variety of vaccine systems for delivery of immunoreactive epitopes are known in the art (see, e.g., Heryin et al., Ann Med 1999 Feb 31(1):66-78; Maruyama et al., Cancer Immunol Immunother 2000 Jun 49(3):123-32) Briefly, such methods of generating an immune response (e.g. humoral and/or cell-mediated) in a mammal, comprise the steps of: exposing the mammal's immune system to an WO 2004/098515 PCT/US2004/013568 50 immunoreactive epitope (e.g. an epitope present in a 109P1 D4 protein shown in Figure 3 or analog or homolog thereof) so that the mammal generates an immune response that is specific for that epitope (e.g. generates antibodies that specifically recognize that epitope). In a preferred method, a 109P1D4 immunogen contains a biological motif, see e.g., Tables Vill-XXI and XXII-XLIX, or a peptide of a size range from 109P1D4 indicated in Figure 5, Figure 6, Figure 7, Figure 8, and Figure 9. The entire 1 09P1 D4 protein, immunogenic regions or epitopes thereof can be combined and delivered by various means. Such vaccine compositions can include, for example, lipopeptides (e.g.,Vitiello, A. et al., J. Clin. Invest. 95:341, 1995), peptide compositions encapsulated in poly(DL-lactide-co-glycolide) ("PLG") microspheres (see, e.g., Eldridge, et al., Molec. Immunol. 28:287-294, 1991: Alonso et al., Vaccine 12:299-306, 1994; Jones et al., Vaccine 13:675-681, 1995), peptide compositions contained in immune stimulating complexes (ISCOMS) (see, e.g., Takahashi et al., Nature 344:873 875, 1990; Hu et al., Clin Exp Immunol. 113:235-243, 1998), multiple antigen peptide systems (MAPs) (see e.g., Tam, J. P., Proc. Nat/. Acad. Sci. U.S.A. 85:5409-5413, 1988; Tam, J.P., J. Immunol. Methods 196:17-32, 1996), peptides formulated as multivalent peptides; peptides for use in ballistic delivery systems, typically crystallized peptides, viral delivery vectors (Perkus, M. E. et al., In: Concepts in vaccine development, Kaufmann, S. H. E., ed., p. 379, 1996; Chakrabarti, S. et al., Nature 320:535, 1986; Hu, S. L. et a., Nature 320:537, 1986; Kieny, M.-P. et a., AIDS Bio/Technology 4:790, 1986; Top, F. H. et al., J. Infect. Dis. 124:148, 1971; Chanda, P. K. et al., Virology 175:535, 1990), particles of viral or synthetic origin (e.g., Kofler, N. et al., J. !mmunol. Methods. 192:25, 1996; Eldridge, J. H. et al., Sem. Hematol. 30:16, 1993; Falo, L. D., Jr. et al., Nature Med. 7:649,1995), adjuvants (Warren, H. S., Vogel, F. R., and Chedid, L. A. Annu. Rev. !mmunol. 4:369,1986; Gupta, R. K. et al., Vaccine 11:293, 1993), liposomes (Reddy, R. et al., J. !mmunol. 148:1585,1992; Rock, K. L, Immunol. Today 17:131, 1996), or, naked or particle absorbed cDNA (Ulmer, J. B. et al., Science 259:1745, 1993; Robinson, H. L., Hunt, L. A., and Webster, R. G., Vaccine 11:957,1993; Shiver, J. W. et al., In: Concepts in vaccine development, Kaufmann, S. H. E., ed., p. 423,1996; Cease, K. B., and Berzofsky, J. A., Annu. Rev. Immunol. 12:923,1994 and Eldridge, J. H. etaL., Sem. Hematol. 30:16, 1993). Toxin-targeted delivery technologies, also known as receptor mediated targeting, such as those of Avant Immunotherapeutics, Inc. (Needham, Massachusetts) may also be used, In patients with 109P1 D4-associated cancer, the vaccine compositions of the invention can also be used in conjunction with other treatments used for cancer, e.g., surgery, chemotherapy, drug therapies, radiation therapies, etc. including use in combination with immune adjuvants such as IL-2, IL-12, GM-CSF, and the like. Cellular Vaccines: CTL epitopes can be determined using specific algorithms to identify peptides within 109P1 D4 protein that bind corresponding HLA alleles (see e.g., Table IV; EpimerTM and Epimatrix

TM

, Brown University (URL brown.edu/Research/TB HIVLablepimatrix/epimatrx.html); and, BIMAS, (URL bimas.dcrt.nih.gov/; SYFPEITHI at URL syfpeithi.bmi-heidelberg.com/). In a preferred embodiment, a 109P1D4 immunogen contains one or more amino acid sequences identified using techniques well known in the art, such as the sequences shown in Tables VIII-XXI and XXII-XLIX or a peptide of 8, 9, 10 or 11 amino acids specified by an HLA Class I motif/supermotif (e.g., Table IV (A), Table IV (D), or Table IV (E)) and/or a peptide of at least 9 amino acids that comprises an HLA Class 11 motif/supermotif (e.g., Table IV (B) or Table IV (C)). As is appreciated in the art, the HLA Class I binding groove is essentially closed ended so that peptides of only a particular size range can fit into the groove and be bound, generally HLA Class I epitopes are 8, 9, 10, or 11 amino acids long. In contrast, the HLA Class 11 binding groove is essentially open end6d; therefore a peptide of about 9 or more amino acids can be bound by an HLA Class 11 molecule. Due to the binding groove differences between HLA Class I and II, HLA Class I motifs are length specific, i.e., position two of a Class I motif is the second amino acid in an amino to carboxyl direction of the peptide. The amino acid positions in a Class 11 motif are relative only to each other, not the overall peptide, i.e., additional amino acids can be attached to the amino and/or carboxyl termini of a motif-bearing sequence. HLA Class II epitopes are often 9, 10, 11, 12, 13, WO 2004/098515 PCT/US2004/013568 51 14,15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 amino acids long, or longer than 25 amino acids. Antibody-based Vaccines A wide variety of methods for generating an immune response in a mammal are known in the art (for example as the first step in the generation of hybridomas). Methods of generating an immune response in a mammal comprise exposing the mammal's immune system to an immunogenic epitope on a protein (e.g. a 109P1D4 protein) so that an immune response is generated. A typical embodiment consists of a method for generating an immune response to 109P1D4 in a host, by contacting the host with a sufficient amount of at least one 109P1D4 B cell or cytotoxic T-cell epitope or analog thereof; and at least one periodic interval thereafter re-contacting the host with the 109P1 D4 B cell or cytotoxic T-cell epitope or analog thereof. A specific embodiment consists of a method of generating an immune response against a 109P1 D4 related protein or a man-made multiepitopic peptide comprising: administering 109P1D4 immunogen (e.g. a 109P1D4 protein or a peptide fragment thereof, a 109P1D4 fusion protein or analog etc.) in a vaccine preparation to a human or another mammal. Typically, such vaccine preparations further contain a suitable adjuvant (see, e.g., U.S. Patent No. 6,146,635) or a universal helper epitope such as a PADRETMpeptide (Epimmune Inc., San Diego, CA; see, e.g., Alexander et a., J. Immunol. 2000 164(3); 164(3): 1625-1633; Alexander et a., Immunity 1994 1(9): 751-761 and Alexander et a., Immunol, Res. 1998 18(2): 79-92). An alternative method comprises generating an immune response in an individual against a 109P1 D4 immunogen by: administering in vivo to muscle or skin of the individual's body a DNA molecule that comprises a DNA sequence that encodes a 109P1D4 immunogen, the DNA sequence operatively linked to regulatory sequences which control the expression of the DNA sequence; wherein the DNA molecule is taken up by cells, the DNA sequence is expressed in the cells and an immune response is generated against the immunogen (see, e.g., U.S. Patent No. 5,962,428). Optionally a genetic vaccine facilitator such as anionic lipids; saponins; lectins; estrogenic compounds; hydroxylated lower alkyls; dimethyl sulfoxide; and urea is also administered. In addition, an antiidiotypic antibody can be administered that mimics 109P1D4, in order to generate a response to the target antigen. Nucleic Acid Vaccines: Vaccine compositions of the invention include nucleic acid-mediated modalities. DNA or RNA that encode protein(s) of the invention can be administered to a patient. Genetic immunization methods can be employed to generate prophylactic or therapeutic humoral and cellular immune responses directed against cancer cells expressing 109P1 D4. Constructs comprising DNA encoding a 109P1D4-related protein/immunogen and appropriate regulatory sequences can be injected directly into muscle or skin of an individual, such that the cells of the muscle or skin take-up the construct and express the encoded 109P1D4 protein/immunogen. Alternatively, a vaccine comprises a 109P1 D4-related protein. Expression of the 109P1 D4-related protein immunogen results in the generation of prophylactic or therapeutic humoral and cellular immunity against cells that bear a 109P1D4 protein. Various prophylactic and therapeutic genetic immunization techniques known in the art can be used (for review, see information and references published at Internet address genweb.com). Nucleic acid-based delivery is described, for instance, in Wolff et. al., Science 247:1465 (1990) as well as U.S. Patent Nos, 5,580,859; 5,589,466; 5,804,566; 5,739,118; 5,736,524; 5,679,647; WO 98104720, Examples of DNA based delivery technologies include "naked DNA", facilitated (bupivicaine, polymers, peptide-mediated) delivery, cationic lipid complexes, and particle-mediated ("gene gun") or pressure-mediated delivery (see, e.g., U.S. Patent No. 5,922,687). For therapeutic or prophylactic immunization purposes, proteins of the invention can be expressed via viral or bacterial vectors. Various viral gene delivery systems that can be used in the practice of the invention include, but are not limited to, vaccinia, fowlpox, canarypox, adenovirus, influenza, poliovirus, adeno-associated virus, lentivirus, and sindbis virus (see, e.g., Restifo, 1996, Curr. Opin. Immunol. 8:658-663; Tsang et al. J. Nail. Cancer Inst. 87:982-990 (1995)). Non-viral delivery systems can also be employed by introducing naked DNA encoding a 109P1D4-related protein into the patient (e.g., intramuscularly or WO 2004/098515 PCT/US2004/013568 52 intradermally) to induce an anti-tumor response. Vaccinia virus is used, for example, as a vector to express nucleotide sequences that encode the peptides of the invention. Upon introduction into a host, the recombinant vaccinia virus expresses the protein immunogenic peptide, and thereby elicits a host immune response, Vaccinia vectors and methods useful in immunization protocols are described in, e.g., U.S. Patent No. 4,722,848. Another vector is BCG (Bacille Calmette Guerin). BCG vectors are described in Stover et a., Nature 351:456-460 (1991). A wide variety of other vectors useful for therapeutic administration or immunization of the peptides of the invention, e.g. adeno and adeno-associated virus vectors, retroviral vectors, Salmonella typhi vectors, detoxified anthrax toxin vectors, and the like, will be apparent to those skilled in the art from the description herein. Thus, gene delivery systems are used to deliver a 109P1 D4-related nucleic acid molecule. In one embodiment, the full length human 109P1D4 cDNA is employed. In another embodiment, 109P1D4 nucleic acid molecules encoding specific cytotoxic T lymphocyte (CTL) and/or antibody epitopes are employed. Ex Vivo Vaccines Various ex vivo strategies can also be employed to generate an immune response. One approach involves the use of antigen presenting cells (APCs) such as dendritic cells (DC) to present 109P1D4 antigen to a patients immune system. Dendritic cells express MHC class I and I molecules, B7 co-stimulator, and IL-1 2, and are thus highly specialized antigen presenting cells. In prostate cancer, autologous dendritic cells pulsed with peptides of the prostate-specific membrane antigen (PSMA) are being used in a Phase I clinical trial to stimulate prostate cancer patients' immune systems (Tjoa et al., 1996, Prostate 28:65 69; Murphy et al., 1996, Prostate 29:371-380). Thus, dendritic cells can be used to present 109P1D4 peptides to T cells in the context of MHC class I or If molecules. In one embodiment, autologous dendritic cells are pulsed with 109P1 D4 peptides capable of binding to MHC class I and/or class II molecules. In another embodiment, dendritic cells are pulsed with the complete 109P1D4 protein. Yet another embodiment involves engineering the overexpression of a 109P1D4 gene in dendritic cells using various implementing vectors known in the art, such as adenovirus (Arthur et al., 1997, Cancer Gene Ther. 4:17-25), retrovirus (Henderson et al., 1996, Cancer Res. 56:3763-3770), lentivirus, adeno-associated virus, DNA transfection (Ribas et al., 1997, Cancer Res. 57:2865-2869), or tumor-derived RNA transfection (Ashley et al., 1997, J. Exp. Med. 186:1177-1182). Cells that express 109P1D4 can also be engineered to express immune modulators, such as GM CSF, and used as immunizing agents. X.B.) 109P1 D4 as a Target for Antibody-based Therapy 109P1D4 is an attractive target for antibody-based therapeutic strategies. A number of antibody strategies are known in the art for targeting both extracellular and intracellular molecules (see, e.g., complement and ADCC mediated killing as well as the use of intrabodies). Because 109P1D4 is expressed by cancer cells of various lineages relative to corresponding normal cells, systemic administration of 109P1 D4-immunoreactive compositions are prepared that exhibit excellent sensitivity without toxic, non-specific and/or non-target effects caused by binding of the immunoreactive composition to non-target organs and tissues. Antibodies specifically reactive with domains of 109P1D4 are useful to treat 109P1D4-expressing cancers systemically, either as conjugates with a toxin or therapeutic agent, or as naked antibodies capable of inhibiting cell proliferation or function. 109P1D4 antibodies can be introduced into a patient suchthat the antibody binds to 109P1D4 and modulates a function, such as an interaction with a binding partner, and consequently mediates destruction of the tumor cells and/or inhibits the growth of the tumor cells. Mechanisms by which such antibodies exert a therapeutic effect can include complement-mediated cytolysis, antibody-dependent cellular cytotoxicity, modulation of the physiological function of 109P1 D4, inhibition of ligand binding or signal transduction pathways, modulation of tumor cell differentiation, alteration of WO 2004/098515 PCT/US2004/013568 53 tumor angiogenesis factor profiles, and/or apoptosis. Those skilled in the art understand that antibodies can be used to specifically target and bind immunogenic molecules such as an immunogenic region of a 109P1 D4 sequence shown in Figure 2 or Figure 3. In addition, skilled artisans understand that it is routine to conjugate antibodies to cytotoxic agents (see, e.g., Slevers et a. Blood 93:11 3678 3684 (June 1, 1999)). When cytotoxic and/or therapeutic agents are delivered directly to cells, such as by conjugating them to antibodies specific for a molecule expressed by that cell (e.g. 109P1 D4), the cytotoxic agent will exert its known biological effect (i.e. cytotoxicity) on those cells. A wide variety of compositions and methods for using antibody-cytotoxic agent conjugates to kill cells are known in the art. In the context of cancers, typical methods entail administering to an animal having a tumor a biologically effective amount of a conjugate comprising a selected cytotoxic and/or therapeutic agent linked to a targeting agent (e.g. an anti 109P1 D4 antibody) that binds to a marker (e.g. 109P1 D4) expressed, accessible to binding or localized on the cell surfaces. A typical embodiment is a method of delivering a cytotoxic and/or therapeutic agent to a cell expressing 109P1 D4, comprising conjugating the cytotoxic agent to an antibody that immunospecifically binds to a 109P1 D4 epitope, and, exposing the cell to the antibody-agent conjugate. Another illustrative embodiment is a method of treating an individual suspected of suffering from metastasized cancer, comprising a step of administering parenterally to said individual a pharmaceutical composition comprising a therapeutically effective amount of an antibody conjugated to a cytotoxic and/or therapeutic agent. Cancer immunotherapy using anti-109P1D4 antibodies can be done in accordance with various approaches that have been successfully employed in the treatment of other types of cancer, including but not limited to colon cancer (Arlen et al., 1998, Crit. Rev. Immunol. 18:133-138), multiple myeloma (Ozaki et a., 1997, Blood 90:3179-3186, Tsunenari et a., 1997, Blood 90:2437-2444), gastric cancer (Kasprzyk et a., 1992, Cancer Res. 52:2771-2776), B-cell lymphoma (Funakoshi et a., 1996, J. Immunother. Emphasis Tumor Immunol. 19:93-101), leukemia (Zhong et at., 1996, Leuk. Res. 20:581-589), colorectal cancer (Moun et al., 1994, Cancer Res. 54:6160-6166; Velders et al., 1995, Cancer Res. 55:4398-4403), and breast cancer (Shepard et a., 1991, J. Clin. Immunol. 11:117-127). Some therapeutic approaches involve conjugation of naked antibody to a toxin or radioisotope, such as the conjugation of Y 9 1 or 1131 to anti-CD20 antibodies (e.g., ZevalinTM, IDEC Pharmaceuticals Corp. or BexxarTM, Coulter Pharmaceuticals), while others involve co-administration of antibodies and other therapeutic agents, such as HerceptinTM (trastuzumab) with paclitaxel (Genentech, Inc.). The antibodies can be conjugated to a therapeutic agent. To treat prostate cancer, for example, 109P1 D4 antibodies can be administered in conjunction with radiation, chemotherapy or hormone ablation. Also, antibodies can be conjugated to a toxin such as calicheamicin (e.g., Mylotargm, Wyeth-Ayerst, Madison, NJ, a recombinant humanized IgG4 kappa antibody conjugated to antitumor antibiotic calicheamicin) or a maytansinoid (e.g., taxane-based Tumor-Activated Prodrug, TAP, platform, ImmunoGen, Cambridge, MA, also see e.g., US Patent 5,416,064). Although 109P1 D4 antibody therapy is useful for all stages of cancer, antibody therapy can be particularly appropriate in advanced or metastatic cancers. Treatment with the antibody therapy of the invention is indicated for patients who have received one or more rounds of chemotherapy. Alternatively, antibody therapy of the invention is combined with a chemotherapeutic or radiation regimen for patients who have not received chemotherapeutic treatment. Additionally, antibody therapy can enable the use of reduced dosages of concomitant chemotherapy, particularly for patients who do not tolerate the toxicity of the chemotherapeutic agent very well. Fan et al. (Cancer Res. 53:4637-4642, 1993), Prewett et al. (International J. of Onco. 9:217-224, 1996), and Hancock et al. (Cancer Res. 51:4575-4580, 1991) describe the use of various antibodies together with chemotherapeutic agents. Although 109P1 D4 antibody therapy is useful for all stages of cancer, antibody therapy can be particularly WO 2004/098515 PCT/US2004/013568 54 appropriate in advanced or metastatic cancers. Treatment with the antibody therapy of the invention is indicated for patients who have received one or more rounds of chemotherapy. Alternatively, antibody therapy of the invention is combined with a chemotherapeutic or radiation regimen for patients who have not received chemotherapeutic treatment. Additionally, antibody therapy can enable the use of reduced dosages of concomitant chemotherapy, particularly for patients who do not tolerate the toxicity of the chemotherapeutic agent very well. Cancer patients can be evaluated for the presence and level of 109P1 D4 expression, preferably using immunohistochemical assessments of tumor tissue, quantitative 109P1 D4 imaging, or other techniques that reliably indicate the presence and degree of 109P1D4 expression. Immunohistochemical analysis of tumor biopsies or surgical specimens is preferred for this purpose. Methods for immunohistochemical analysis of tumor tissues are well known in the art. Anti-I 09P1 D4 monoclonal antibodies that treat prostate and other cancers include those that initiate a potent immune response against the tumor or those that are directly cytotoxic. In this regard, anti-109P1D4 monoclonal antibodies (mAbs) can elicit tumor cell lysis by either complement-mediated or antibody-dependent cell cytotoxicity (ADCC) mechanisms, both of which require an intact Fc portion of the immunoglobulin molecule for interaction with effector cell Fc receptor sites on complement proteins. In addition, anti-109P1D4 mAbs that exert a direct biological effect on tumor growth are useful to treat cancers that express 109P1 D4. Mechanisms by which directly cytotoxic mAbs act include: inhibition of cell growth, modulation of cellular differentiation, modulation of tumor angiogenesis factor profiles, and the induction of apoptosis. The mechanism(s) by which a particular anti-109P1D4 mAb exerts an anti-tumor effect is evaluated using any number of in vitro assays that evaluate cell death such as ADCC, ADMMC, complement-mediated cell lysis, and so forth, as is generally known in the art. In some patients, the use of murine or other non-human monoclonal antibodies, or human/mouse chimeric mAbs can induce moderate to strong immune responses against the non-human antibody. This can result in clearance of the antibody from circulation and reduced efficacy. In the most severe cases, such an immune response can lead to the extensive formation of immune complexes which, potentially, can cause renal failure. Accordingly, preferred monoclonal antibodies used in the therapeutic methods of the invention are those that are either fully human or humanized and that bind specifically to the target 109P1 D4 antigen with high affinity but exhibit low or no antigenicity in the patient. Therapeutic methods of the invention contemplate the administration of single anti-I 09P1 D4 mAbs as well as combinations, or cocktails, of different mAbs. Such mAb cocktails can have certain advantages inasmuch as they contain mAbs that target different epitopes, exploit different effector mechanisms or combine directly cytotoxic mAbs with mAbs that rely on immune effector functionality. Such mAbs in combination can exhibit synergistic therapeutic effects. In addition, anti 109P1 D4 mAbs can be administered concomitantly with other therapeutic modalities, including but not limited to various chemotherapeutic agents, androgen-blockers, immune modulators (e.g., IL-2, GM-CSF), surgery or radiation. The anti 109P1D4 mAbs are administered in their "naked" or unconjugated form, or can have a therapeutic agent(s) conjugated to them. Anti-109P1D4 antibody formulations are administered via any route capable of delivering the antibodies to a tumor cell. Routes of administration include, but are not limited to, intravenous, intraperitoneal, intramuscular, intratumor, intradermal, and the like. Treatment generally involves repeated administration of the anti-I 09P1D4 antibody preparation, via an acceptable route of administration such as intravenous injection (IV), typically at a dose in the range of about 0.1, .2, .3,.4,.5,.6,.7, .8.9., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, or 25 mg/kg body weight. In general, doses in the range of 10-1000 mg mAb per week are effective and well tolerated. Based on clinical experience with the HerceptinTM mAb in the treatment of metastatic breast cancer, an initial loading dose of approximately 4 mg/kg patient body weight IV, followed by weekly doses of about 2 mg/kg IV of the anti- WO 2004/098515 PCT/US2004/013568 55 1 09P1 D4 mAb preparation represents an acceptable dosing regimen. Preferably, the initial loading dose is administered as a 90-minute or longer infusion. The periodic maintenance dose is administered as a 30 minute or longer infusion, provided the initial dose was well tolerated. As appreciated by those of skill in the art, various factors can influence the ideal dose regimen in a particular case. Such factors include, for example, the binding affinity and half life of the Ab or mAbs used, the degree of 109P1D4 expression in the patient, the extent of circulating shed 109P1 D4 antigen, the desired steady-state antibody concentration level, frequency of treatment, and the influence of chemotherapeutic or other agents used in combination with the treatment method of the invention, as well as the health status of a particular patient. Optionally, patients should be evaluated for the levels of 109P1D4 in a given sample (e.g. the levels of circulating 109P1D4 antigen andlor 109P1D4 expressing cells) in order to assist in the determination of the most effective dosing regimen, etc. Such evaluations are also used for monitoring purposes throughout therapy, and are useful to gauge therapeutic success in combination with the evaluation of other parameters (for example, urine cytology and/or ImmunoCyt levels in bladder cancer therapy, or by analogy, serum PSA levels in prostate cancer therapy). Anti-idiotypic anti-109P1 D4 antibodies can also be used in anti-cancer therapy as a vaccine for inducing an immune response to cells expressing a 109P1D4-related protein. In particular, the generation of anti-idiotypic antibodies is well known in the art; this methodology can readily be adapted to generate anti-idiotypic anti-109P1 D4 antibodies that mimic an epitope on a 109P1 4-related protein (see, for example, Wagner et al., 1997, Hybridoma 16: 33-40; Foon et af., 1995, J. Clin. Invest. 96:334-342; Herlyn etal., 1996, Cancer Immunol. Immunother. 43:65-76). Such an anti-idiotypic antibody can be used in cancer vaccine strategies. X.C.) 109P1 D4 as a Target for Cellular Immune Responses Vaccines and methods of preparing vaccines that contain an immunogenically effective amount of one or more HLA-binding peptides as described herein are further embodiments of the invention. Furthermore, vaccines in accordance with the invention encompass compositions of one or more of the claimed peptides. A peptide can be present in a vaccine individually. Alternatively, the peptide can exist as a homopolymer comprising multiple copies of the same peptide, or as a heteropolymer of various peptides. Polymers have the advantage of increased immunological reaction and, where different peptide epitopes are used to make up the polymer, the additional ability to induce antibodies and/or CTLs that react with different antigenic determinants of the pathogenic organism or tumor-related peptide targeted for an immune response. The composition can be a naturally occurring region of an antigen or can be prepared, e.g., recombinantly or by chemical synthesis. Carriers that can be used with vaccines of the invention are well known in the art, and include, e.g., thyroglobulin, albumins such as human serum albumin, tetanus toxoid, polyamino acids such as poly L-lysine, poly L-glutamic acid, influenza, hepatitis B virus core protein, and the like. The vaccines can contain a physiologically tolerable (i.e., acceptable) diluent such as water, or saline, preferably phosphate buffered saline. The vaccines also typically include an adjuvant. Adjuvants such as incomplete Freund's adjuvant, aluminum phosphate, aluminum hydroxide, or alum are examples of materials well known in the art. Additionally, as disclosed herein, CTL responses can be primed by conjugating peptides of the invention to lipids, such as tripalmitoyl-S-glyceryfcysteinlyseryl- serine (P 3 CSS). Moreover, an adjuvant such as a synthetic cytosine-phosphorothiolated-guanine-containing (CpG) oligonucleotides has been found to increase CTL responses 10- to 100-fold. (see, e.g. Davila and Cells, J. Immunol. 165:539-547 (2000)) Upon immunization with a peptide composition in accordance with the invention, via injection, aerosol, oral, transdermal, transmucosal, intrapleural, intrathecal, or other suitable routes, the immune system of the host responds to the vaccine by producing large amounts of CTLs and/or HTLs specific for the desired antigen. Consequently, the host becomes WO 2004/098515 PCT/US2004/013568 56 at least partially immune to later development of cells that express or overexpress 109P1D4 antigen, or derives at least some therapeutic benefit when the antigen was tumor-associated. in some embodiments, it may be desirable to combine the class I peptide components with components that induce or facilitate neutralizing antibody and or helper T cell responses directed to the target antigen. A preferred embodiment of such a composition comprises class I and class 1i epitopes in accordance with the invention. An alternative embodiment of such a composition comprises a class I and/or class Il epitope in accordance with the invention, along with a cross reactive HTL epitope such as PADRETM (Epimmune, San Diego, CA) molecule (described e.g., in U.S. Patent Number 5,736,142). A vaccine of the invention can also include antigen-presenting cells (APC), such as dendritic cells (DC), as a vehicle to present peptides of the invention. Vaccine compositions can be created in vitro, following dendritic cell mobilization and harvesting, whereby loading of dendritic cells occurs in vitro. For example, dendritic cells are transfected, e.g., with a minigene in accordance with the invention, or are pulsed with peptides. The dendritic cell can then be administered to a patient to elicit immune responses in vivo. Vaccine compositions, either DNA- or peptide-based, can also be administered in vivo in combination with dendritic cell mobilization whereby loading of dendritic cells occurs in vivo. Preferably, the following principles are utilized when selecting an array of epitopes for inclusion in a polyepitopic composition for use in a vaccine, or for selecting discrete epitopes to be included in a vaccine and/or to be encoded by nucleic acids such as a minigene. It is preferred that each of the following principles be balanced in order to make the selection, The multiple epitopes to be incorporated in a given vaccine composition may be, but need not be, contiguous in sequence in the native antigen from which the epitopes are derived. 1.) Epitopes are selected which, upon administration, mimic immune responses that have been observed to be correlated with tumor clearance. For HLA Class I this includes 3-4 epitopes that come from at least one tumor associated antigen (TAA). For HLA Class 11 a similar rationale is employed; again 3-4 epitopes are selected from at least one TAA (see, e.g., Rosenberg et al., Science 278:1447-1450). Epitopes from one TAA may be used in combination with epitopes from one or more additional TAAs to produce a vaccine that targets tumors with varying expression patterns of frequently-expressed TAAs. 2.) Epitopes are selected that have the requisite binding affinity established to be correlated with immunogenicity: for HLA Class I an ICo of 500 nM or less, often 200 nM or less; and for Class I an ICo of 1000 nM or less. 3.) Sufficient supermotif bearing-peptides, or a sufficient array of allele-specific motif-bearing peptides, are selected to give broad population coverage. For example, it is preferable to have at least 80% population coverage. A Monte Carlo analysis, a statistical evaluation known in the art, can be employed to assess the breadth, or redundancy of, population coverage. 4.) When selecting epitopes from cancer-related antigens it is often useful to select analogs because the patient may have developed tolerance to the native epitope. 5.) Of particular relevance are epitopes referred to as "nested epitopes." Nested epitopes occur where at least two epitopes overlap in a given peptide sequence. A nested peptide sequence can comprise B cell, HLA class I and/or HLA class li epitopes. When providing nested epitopes, a general objective is to provide the greatest number of epitopes per sequence. Thus, an aspect is to avoid providing a peptide that is any longer than the amino terminus of the amino terminal epitope and the carboxyl terminus of the carboxyl terminal epitope in the peptide. When providing a multi-epitopic sequence, such as a sequence comprising nested epitopes, it is generally important to screen the sequence in order to insure that it does not have pathological or other deleterious biological properties. 6.) If a polyepitopic protein is created, or when creating a minigene, an objective is to generate the smallest WO 2004/098515 PCT/US2004/013568 57 peptide that encompasses the epitopes of interest. This principle is similar, if not the same as that employed when selecting a peptide comprising nested epitopes. However, with an artificial polyepitopic peptide, the size minimization objective is balanced against the need to integrate any spacer sequences between epitopes in the polyepitopic protein. Spacer amino acid residues can, for example, be introduced to avoid junctional epitopes (an epitope recognized by the immune system, not present in the target antigen, and only created by the man-made juxtaposition of epitopes), or to facilitate cleavage between epitopes and thereby enhance epitope presentation. Junctional epitopes are generally to be avoided because the recipient may generate an immune response to that non-native epitope. Of particular concern is a junctional epitope that is a "dominant epitope." A dominant epitope may lead to such a zealous response that immune responses to other epitopes are diminished or suppressed. 7.) Where the sequences of multiple variants of the same target protein are present, potential peptide epitopes can also be selected on the basis of their conservancy. For example, a criterion for conservancy may define that the entire sequence of an HLA class I binding peptide or the entire 9-mer core of a class 1i binding peptide be conserved in a designated percentage of the sequences evaluated for a specific protein antigen. X.C.i. Minigene Vaccines A number of different approaches are available which allow simultaneous delivery of multiple epitopes. Nucleic acids encoding the peptides of the invention are a particularly useful embodiment of the invention. Epitopes for inclusion in a minigene are preferably selected according to the guidelines set forth in the previous section. A preferred means of administering nucleic acids encoding the peptides of the invention uses minigene constructs encoding a peptide comprising one or multiple epitopes of the invention. The use of muiti-epitope minigenes is described below and in, Ishioka et a., J. Immunol. 162:3915-3925, 1999; An, L. and Whitton, J. L., J. Virol. 71:2292, 1997; Thomson, S. A. et a., J. Immunol. 157:822, 1996; Whitton, J. L. et al., J. Virol. 67:348, 1993; Hanke, R. et al., Vaccine 16:426, 1998. For example, a multi-epitope DNA plasmid encoding supermotif and/or motif-bearing epitopes derived 109P1D4, the PADRE@ universal helper T cell epitope or multiple HTL epitopes from 109P1D4 (see e.g., Tables VIII-XXI and XXII to XLIX), and an endoplasmic reticulum-translocating signal sequence can be engineered. A vaccine may also comprise epitopes that are derived from other TAAs. The immunogenicity of a multi-epitopic minigene can be confirmed in transgenic mice to evaluate the magnitude of CTL induction responses against the epitopes tested. Further, the immunogenicity of DNA-encoded epitopes in vivo can be correlated with the in vitro responses of specific CTL lines against target cells transfected with the DNA plasmid. Thus, these experiments can show that the minigene serves to both: 1,) generate a CTL response and 2.) that the induced CTLs recognized cells expressing the encoded epitopes. For example, to create a DNA sequence encoding the selected epitopes (minigene) for expression in human cells, the amino acid sequences of the epitopes may be reverse translated. A human codon usage table can be used to guide the codon choice for each amino acid. These epitope-encoding DNA sequences may be directly adjoined, so that when translated, a continuous polypeptide sequence is created. To optimize expression andlor immunogenicity, additional elements can be incorporated into the minigene design. Examples of amino acid sequences that can be reverse translated and included in the minigene sequence include: HLA class I epitopes, HLA class 11 epitopes, antibody epitopes, a ubiquitination signal sequence, and/or an endoplasmic reticulum targeting signal. In addition, HLA presentation of CTL and HTL epitopes may be improved by including synthetic (e.g. poly-alanine) or naturally-occurring flanking sequences adjacent to the CTL or HTL epitopes; these larger peptides comprising the epitope(s) are within the scope of the invention. The minigene sequence may be converted to DNA by assembling oligonucleotides that encode the plus and minus strands of the minigene. Overlapping oligonucleotides (30-100 bases long) may be synthesized, phosphorylated, purified WO 2004/098515 PCT/US2004/013568 58 and annealed under appropriate conditions using well known techniques. The ends of the oligonucleotides can be joined, for example, using T4 DNA ligase. This synthetic minigene, encoding the epitope polypeptide, can then be cloned into a desired expression vector. Standard regulatory sequences well known to those of skill in the art are preferably included in the vector to ensure expression in the target cells. Several vector elements are desirable: a promoter with a down-stream cloning site for minigene insertion; a polyadenylation signal for efficient transcription termination; an E coli origin of replication; and an E. col selectable marker (e.g. ampicillin or kanamycin resistance). Numerous promoters can be used for this purpose, e.g., the human cytomegalovirus (hCMV) promoter. See, e.g., U.S. Patent Nos. 5,580,859 and 5,589,466 for other suitable promoter sequences. Additional vector modifications may be desired to optimize minigene expression and immunogenicity. In some cases, introns are required for efficient gene expression, and one or more synthetic or naturally-occurring introns could be incorporated into the transcribed region of the minigene. The inclusion of mRNA stabilization sequences and sequences for replication in mammalian cells may also be considered for increasing minigene expression. Once an expression vector is selected, the minigene is cloned into the polylinker region downstream of the promoter. This plasmid is transformed into an appropriate E coli strain, and DNA is prepared using standard techniques. The orientation and DNA sequence of the minigene, as well as all other elements included in the vector, are confirmed using restriction mapping and DNA sequence analysis. Bacterial cells harboring the correct plasmid can be stored as a master cell bank and a working cell bank. In addition, immunostimulatory sequences (ISSs or CpGs) appear to play a role in the immunogenicity of DNA vaccines. These sequences may be included in the vector, outside the minigene coding sequence, if desired to enhance immunogenicity. In some embodiments, a bi-cistronic expression vector which allows production of both the minigene-encoded epitopes and a second protein (included to enhance or decrease immunogenicity) can be used. Examples of proteins or polypeptides that could beneficially enhance the immune response if co-expressed include cytokines (e.g., IL-2, IL-1 2, GM CSF), cytokine-inducing molecules (e.g., LeIF), costimulatory molecules, or for HTL responses, pan-DR binding proteins

(PADRE

T

M, Epimmune, San Diego, CA). Helper (HTL) epitopes can be joined to intracellular targeting signals and expressed separately from expressed CTL epitopes; this allows direction of the HTL epitopes to a cell compartment different than that of the CTL epitopes. If required, this could facilitate more efficient entry of HTL epitopes into the HLA class I pathway, thereby improving HTL induction. In contrast to HTL or CTL induction, specifically decreasing the immune response by co-expression of immunosuppressive molecules (e.g. TGF-p) may be beneficial in certain diseases. Therapeutic quantities of plasmid DNA can be produced for example, by fermentation in E coli, followed by purification. Aliquots from the working cell bank are used to inoculate growth medium, and grown to saturation in shaker flasks or a bioreactor according to well-known techniques. Plasmid DNA can be purified using standard bioseparation technologies such as solid phase anion-exchange resins supplied by QIAGEN, Inc. (Valencia, California). If required, supercolled DNA can be isolated from the open circular and linear forms using gel electrophoresis or other methods. Purified plasmid DNA can be prepared for injection using a variety of formulations. The simplest of these is reconstitution of lyophilized DNA in sterile phosphate-buffer saline (PBS). This approach, known as "naked DNA," is currently being used for intramuscular (IM) administration in clinical trials. To maximize the immunotherapeutic effects of minigene DNA vaccines, an alternative method for formulating purified plasmid DNA may be desirable. A variety of methods have been described, and new techniques may become available. Cationic lipids, glycolipids, and fusogenic liposomes can also be used in the formulation (see, e.g., as described by WO 93/24640; Mannino & Gould-Fogerite, BioTechniques 6(7): WO 2004/098515 PCT/US2004/013568 59 682 (1988); U.S. Pat No. 5,279,833; WO 91/06309; and Feigner, et aL., Proc. Nat'l Acad. Sci. USA 84:7413 (1987). In addition, peptides and compounds referred to collectively as protective, interactive, non-condensing compounds (PINC) could also be complexed to purified plasmid DNA to influence variables such as stability, intramuscular dispersion, or trafficking to specific organs or cell types. Target cell sensitization can be used as a functional assay for expression and HLA class I presentation of minigene-encoded CTL epitopes. For example, the plasmid DNA is introduced into a mammalian cell line that is suitable as a target for standard CTL chromium release assays. The transfection method used will be dependent on the final formulation. Electroporation can be used for "naked" DNA, whereas cationic lipids allow direct in vitro transfection. A plasmid expressing green fluorescent protein (GFP) can be co-transfected to allow enrichment of transfected cells using fluorescence activated cell sorting faces) . These cells are then chromium-51 (51Cr) labeled and used as target cells for epitope-specific CTL lines; cytolysis, detected by 5 1 Cr release, indicates both production of, and HLA presentation of, minigene-encoded CTL epitopes. Expression of HTL epitopes may be evaluated in an analogous manner using assays to assess HTL activity. In vivo immunogenicity is a second approach for functional testing of minigene DNA formulations. Transgenic mice expressing appropriate human HLA proteins are immunized with the DNA product. The dose and route of administration are formulation dependent (e.g., IM for DNA in PBS, intraperitoneal (i.p.) for lipid-complexed DNA). Twenty-one days after immunization, splenocytes are harvested and restimulated for one week in the presence of peptides encoding each epitope being tested. Thereafter, for CTL effector cells, assays are conducted for cytolysis of peptide-loaded, 5 1Cr-labeled target cells using standard techniques. Lysis of target cells that were sensitized by HLA loaded with peptide epitopes, corresponding to minigene-encoded epitopes, demonstrates DNA vaccine function for in vivo induction of CTLs. Immunogenicity of HTL epitopes is confirmed in transgenic mice in an analogous manner. Alternatively, the nucleic acids can be administered using ballistic delivery as described, for instance, in U.S. Patent No. 5,204,253. Using this technique, particles comprised solely of DNA are administered. In a further alternative embodiment, DNA can be adhered to particles, such as gold particles. Minigenes can also be delivered using other bacterial or viral delivery systems well known in the art, e.g., an expression construct encoding epitopes of the invention can be incorporated into a viral vector such as vaccinia. X.C.2. Combinations of CTL Peptides with Helper Peptides Vaccine compositions comprising CTL peptides of the invention can be modified, e.g., analoged, to provide desired attributes, such as improved serum half life, broadened population coverage or enhanced immunogenicity. For instance, the ability of a peptide to induce CTL activity can be enhanced by linking the peptide to a sequence which contains at least one epitope that is capable of inducing a T helper cell response. Although a CTL peptide can be directly linked to a T helper peptide, often CTL epitope/HTL epitope conjugates are linked by a spacer molecule. The spacer is typically comprised of relatively small, neutral molecules, such as amino acids or amino acid mimetics, which are substantially uncharged under physiological conditions. The spacers are typically selected from, e.g., Ala, Gly, or other neutral spacers of nonpolar amino acids or neutral polar amino acids. It will be understood that the optionally present spacer need not be comprised of the same residues and thus may be a hetero- or homo-oligomer. When present, the spacer will usually be at least one or two residues, more usually three to six residues and sometimes 10 or more residues. The CTL peptide epitope can be linked to the T helper peptide epitope either directly or via a spacer either at the amino or carboxy terminus of the CTL peptide. The amino terminus of either the immunogenic peptide or the T helper peptide may be acylated. In certain embodiments, the T helper peptide is one that is recognized by T helper cells present in a majority of a WO 2004/098515 PCT/US2004/013568 60 genetically diverse population. This can be accomplished by selecting peptides that bind to many, most, or all of the HLA class 11 molecules. Examples of such amino acid bind many HLA Class Il molecules include sequences from antigens such as tetanus toxoid at positions 830-843 QYIKANSKFIGITE; (SEQ ID NO: 40), Plasmodium falciparum circumsporozoite (CS) protein at positions 378-398 DIEKKIAKMEKASSVFNVVNS; (SEQ ID NO: 41), and Streptococcus 1 8kD protein at positions 116-131 GAVDSILGGVATYGAA; (SEQ ID NO: 42). Other examples include peptides bearing a DR 1-4-7 supermotif, or either of the DR3 motifs. Alternatively, it is possible to prepare synthetic peptides capable of stimulating T helper lymphocytes, in a loosely HLA-restricted fashion, using amino acid sequences not found in nature (see, eg., PCT publication WO 95/07707). These synthetic compounds called Pan-DR-binding epitopes (e.g., PADRE

T

1A, Epimmune, Inc., San Diego, CA) are designed, most preferably, to bind most HLA-DR (human HLA class ll) molecules. For instance, a pan-DR-binding epitope peptide having the formula: xKXVAAWTLKAAx (SEQ ID NO: 43), where "X"is either cyclohexylalanine, phenylalanine, or tyrosine, and a is either D-alanine or L-alanine, has been found to bind to most HLA-DR alleles, and to stimulate the response of T helper lymphocytes from most individuals, regardless of their HLA type. An alternative of a pan-DR binding epitope comprises all L" natural amino acids and can be provided in the form of nucleic acids that encode the epitope. HTL peptide epitopes can also be modified to alter their biological properties. For example, they can be modified to include D-amino acids to increase their resistance to proteases and thus extend their serum half life, or they can be conjugated to other molecules such as lipids, proteins, carbohydrates, and the like to increase their biological activity. For example, a T helper peptide can be conjugated to one or more palmitic acid chains at either the amino or carboxyl termini. X.C.3. Combinations of CTL Peptides with T Cell Priming Agents In some embodiments it may be desirable to include in the pharmaceutical compositions of the invention at least one component which primes B lymphocytes or T lymphocytes. Lipids have been identified as agents capable of priming CTL in vivo. For example, palmitic acid residues can be attached to the e-and a- amino groups of a lysine residue and then linked, e.g., via one or more linking residues such as Gly, Gly-Gly-, Ser, Ser-Ser, or the like, to an immunogenic peptide. The lipidated peptide can then be administered either directly in a micelle or particle, incorporated into a liposome, or emulsified in an adjuvant, e.g., incomplete Freund's adjuvant. In a preferred embodiment, a particularly effective immunogenic composition comprises palmitic acid attached to e- and u- amino groups of Lys, which is attached via linkage, e.g., Ser-Ser, to the amino terminus of the immunogenic peptide. As another example of lipid priming of CTL responses, E coil lipoproteins, such as tripalmitoyl-S glycerylcysteinlyseryl- serine (P3CSS) can be used to prime virus specific CTL when covalently attached to an appropriate peptide (see, e.g., Deres, et al., Nature 342:561, 1989). Peptides of the invention can be coupled to P3CSS, for example, and the lipopeptide administered to an individual to prime specifically an immune response to the target antigen. Moreover, because the induction of neutralizing antibodies can also be primed with P3CSS-conjugated epitopes, two such compositions can be combined to more effectively elicit both humoral and cell-mediated responses. X.C.4. Vaccine Compositions Comprising DC Pulsed with CTL and/or HTL Peptides An embodiment of a vaccine composition in accordance with the invention comprises ex vivo administration of a cocktail of epitope-bearing peptides to PBMC, or isolated DC therefrom, from the patient's blood. A pharmaceutical to facilitate harvesting of DC can be used, such as Progenipoetin T M (Pharmacia-Monsanto, St. Louis, MO) or GM-CSF/IL-4. After pulsing the DC with peptides and prior to reinfusion into patients, the DC are washed to remove unbound peptides. In this embodiment, a vaccine comprises peptide-pulsed DCs which present the pulsed peptide epitopes complexed with HLA molecules on their surfaces. The DC can be pulsed ex vivo with a cocktail of peptides, some of which stimulate CTL responses to 109P1D4.

WO 2004/098515 PCT/US2004/013568 61 Optionally, a helper T cell (HTL) peptide, such as a natural or artificial loosely restricted HLA Class Il peptide, can be included to facilitate the CTL response. Thus, a vaccine in accordance with the invention is used to treat a cancer which expresses or overexpresses 109P1 D4. X.D. Adoptive Immunotherapy Antigenic 109P1 D4-related peptides are used to elicit a CTL and/or HTL response ex vivo, as well. The resulting CTL or HTL cells, can be used to treat tumors in patients that do not respond to other conventional forms of therapy, or will not respond to a therapeutic vaccine peptide or nucleic acid in accordance with the invention. Ex vivo CTL or HTL responses to a particular antigen are induced by incubating in tissue culture the patient's, or genetically compatible, CTL or HTL precursor cells together with a source of antigen-presenting cells (APC), such as dendritic cells, and the appropriate immunogenic peptide. After an appropriate incubation time (typically about 7-28 days), in which the precursor cells are activated and expanded into effector cells, the cells are infused back into the patient, where they will destroy (CTL) or facilitate destruction (HTL) of their specific target cell (e.g., a tumor cell). Transfected dendritic cells may also be used as antigen presenting cells. X.E. Administration of Vaccines for Therapeutic or Prophylactic Purposes Pharmaceutical and vaccine compositions of the invention are typically used to treat and/or prevent a cancer that expresses or overexpresses 109P1D4. In therapeutic applications, peptide and/or nucleic acid compositions are administered to a patient in an amount sufficient to elicit an effective B cell, CTL and/or HTL response to the antigen and to cure or at least partially arrest or slow symptoms and/or complications. An amount adequate to accomplish this is defined as "therapeutically effective dose." Amounts effective for this use will depend on, e.g., the particular composition administered, the manner of administration, the stage and severity of the disease being treated, the weight and general state of health of the patient, and the judgment of the prescribing physician. For pharmaceutical compositions, the immunogenic peptides of the invention, or DNA encoding them, are generally administered to an individual already bearing a tumor that expresses 109P1 D4. The peptides or DNA encoding them can be administered individually or as fusions of one or more peptide sequences. Patients can be treated with the immunogenic peptides separately or in conjunction with other treatments, such as surgery, as appropriate. For therapeutic use, administration should generally begin at the first diagnosis of 109P1 D4-associated cancer. This is followed by boosting doses until at least symptoms are substantially abated and for a period thereafter. The embodiment of the vaccine composition (i.e., including, but not limited to embodiments such as peptide cocktails, polyepitopic polypeptides, minigenes, or TAA-specific CTLs or pulsed dendritic cells) delivered to the patient may vary according to the stage of the disease or the patient's health status. For example, in a patient with a tumor that expresses 109P1 D4, a vaccine comprising 109P1 D4-specific CTL may be more efficacious in killing tumor cells in patient with advanced disease than alternative embodiments. It is generally important to provide an amount of the peptide epitope delivered by a mode of administration sufficient to stimulate effectively a cytotoxic T cell response; compositions which stimulate helper T cell responses can also be given in accordance with this embodiment of the invention. The dosage for an initial therapeutic immunization generally occurs in a unit dosage range where the lower value is about 1, 5, 50, 500, or 1,000 pg and the higher value is about 10,000; 20,000; 30,000; or 50,000 pg. Dosage values for a human typically range from about 500 pg to about 50,000 pg per 70 kilogram patient. Boosting dosages of between about 1.0 l.tg to about 50,000 sg of peptide pursuant to a boosting regimen over weeks to months may be administered depending WO 2004/098515 PCT/US2004/013568 62 upon the patients response and condition as determined by measuring the specific activity of CTL and HTL obtained from the patient's blood. Administration should continue until at least clinical symptoms or laboratory tests indicate that the neoplasia, has been eliminated or reduced and for a period thereafter. The dosages, routes of administration, and dose schedules are adjusted in accordance with methodologies known in the art. In certain embodiments, the peptides and compositions of the present invention are employed in serious disease states, that is, life-threatening or potentially life threatening situations. In such cases, as a result of the minimal amounts of extraneous substances and the relative nontoxic nature of the peptides in preferred compositions of the invention, it is possible and may be felt desirable by the treating physician to administer substantial excesses of these peptide compositions relative to these stated dosage amounts. The vaccine compositions of the invention can also be used purely as prophylactic agents. Generally the dosage for an initial prophylactic immunization generally occurs in a unit dosage range where the lower value is about 1, 5, 50, 500, or 1000 pg and the higher value is about 10,000; 20,000; 30,000; or 50,000 pg. Dosage values for a human typically range from about 500 pg to about 50,000 pg per 70 kilogram patient. This is followed by boosting dosages of between about 1.0 pg to about 50,000 pg of peptide administered at defined intervals from about four weeks to six months after the initial administration of vaccine. The immunogenicity of the vaccine can be assessed by measuring the specific activity of CTL and HTL obtained from a sample of the patient's blood. The pharmaceutical compositions for therapeutic treatment are intended for parenteral, topical, oral, nasal, intrathecal, or local (e.g. as a cream or topical ointment) administration. Preferably, the pharmaceutical compositions are administered parentally, e.g., intravenously, subcutaneously, intradermally, or intramuscularly. Thus, the invention provides compositions for parenteral administration which comprise a solution of the immunogenic peptides dissolved or suspended in an acceptable carrier, preferably an aqueous carrier. A variety of aqueous carriers may be used, e.g., water, buffered water, 0.8% saline, 0.3% glycine, hyaluronic acid and the like. These compositions may be sterilized by conventional, well-known sterilization techniques, or may be sterile filtered. The resulting aqueous solutions may be packaged for use as is, or lyophilized, the lyophilized preparation being combined with a sterile solution prior to administration. The compositions may contain pharmaceutically acceptable auxiliary substances as required to approximate physiological conditions, such as pH-adjusting and buffering agents, tonicity adjusting agents, wetting agents, preservatives, and the like, for example, sodium acetate, sodium lactate, sodium chloride, potassium chloride, calcium chloride, sorbitan monolaurate, triethanolamine oleate, etc. The concentration of peptides of the invention in the pharmaceutical formulations can vary widely, i.e., from less than about 0.1%, usually at or at least about 2% to as much as 20% to 50% or more by weight, and will be selected primarily by fluid volumes, viscosities, etc., in accordance with the particular mode of administration selected. A human unit dose form of a composition is typically included in a pharmaceutical composition that comprises a human unit dose of an acceptable carrier, in one embodiment an aqueous carrier, and is administered in a volumelquantity that is known by those of skill in the art to be used for administration of such compositions to humans (see, e.g., Remington's Pharmaceutical Sciences, 17th Edition, A. Gennaro, Editor, Mack Publishing Co., Easton, Pennsylvania, 1985). For example a peptide dose for initial immunization can be from about I to about 50,000 pig, generally 100-5,000 pg, for a 70 kg patient. For example, for nucleic acids an initial immunization may be performed using an expression vector in the form of naked nucleic acid administered IM (or SC or ID) in the amounts of 0.5-5 mg at multiple sites. The nucleic acid (0.1 to 1000 pg) can also be administered using a gene gun. Following an incubation period of 3-4 weeks, a booster dose is then administered. The booster can be recombinant fowlpox virus administered at a dose of 5-107 to 5x1 09 pfu.

WO 2004/098515 PCT/US2004/013568 63 For antibodies, a treatment generally involves repeated administration of the anti-109P1D4 antibody preparation, via an acceptable route of administration such as intravenous injection (IV), typically at a dose in the range of about 0.1 to about 10 mg/kg body weight. In general, doses in the range of 10-500 mg mAb per week are effective and well tolerated. Moreover, an initial loading dose of approximately 4 mg/kg patient body weight IV, followed by weekly doses of about 2 mg/kg IV of the anti- 109P1 D4 mAb preparation represents an acceptable dosing regimen. As appreciated by those of skill in the art, various factors can influence the ideal dose in a particular case. Such factors include, for example, half life of a composition, the binding affinity of an Ab, the immunogenicity of a substance, the degree of 109P1 D4 expression in the patient, the extent of circulating shed 109P1 D4 antigen, the desired steady-state concentration level, frequency of treatment, and the influence of chemotherapeutic or other agents used in combination with the treatment method of the invention, as well as the health status of a particular patient. Non-limiting preferred human unit doses are, for example, 5OOpg - 1mg, 1mg - 50mg, 50mg - 100mg, 100mg - 200mg, 200mg - 300mg, 400mg - 500mg, 500mg - 600mg, 600mg - 700mg, 700mg 800mg, 800mg - 900mg, 900mg - 1g, or 1mg - 700mg. In certain embodiments, the dose is in a range of 2-5 mg/kg body weight, e.g., with follow on weekly doses of 1-3 mg/kg; 0.5mg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10mg/kg body weight followed, e.g., in two, three or four weeks by weekly doses; 0.5 - 10mg/kg body weight, e.g., followed in two, three or four weeks by weekly doses; 225, 250, 275, 300, 325, 350, 375, 400mg m 2 of body area weekly; 1-600mg m 2 of body area weekly; 225-400mg m 2 of body area weekly; these does can be followed by weekly doses for 2, 3, 4, 5, 6, 7, 8, 9, 19, 11, 12 or more weeks. In one embodiment, human unit dose forms of polynucleotides comprise a suitable dosage range or effective amount that provides any therapeutic effect. As appreciated by one of ordinary skill in the art a therapeutic effect depends on a number of factors, including the sequence of the polynucleotide, molecular weight of the polynucleotide and route of administration. Dosages are generally selected by the physician or other health care professional in accordance with a variety of parameters known in the art, such as severity of symptoms, history of the patient and the like. Generally, for a polynucleotide of about 20 bases, a dosage range may be selected from, for example, an independently selected lower limit such as about 0.1, 0.25, 0.5, 1, 2, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400 or 500 mg/kg up to an independently selected upper limit, greater than the lower limit, of about 60, 80, 100, 200, 300, 400, 500, 750, 1000, 1500, 2000, 3000, 4000, 5000, 6000, 7000, 8000, 9000 or 10,000 mg/kg. For example, a dose may be about any of the following: 0.1 to 100 mg/kg, 0.1 to 50 mg/kg, 0.1 to 25 mg/kg, 0.1 to 10 mg/kg, I to 500 mg/kg, 100 to 400 mg/kg, 200 to 300 mg/kg, 1 to 100 mg/kg, 100 to 200 mg/kg, 300 to 400 mg/kg, 400 to 500 mg/kg, 500 to 1000 mg/kg, 500 to 5000 mg/kg, or 500 to 10,000 mg/kg. Generally, parenteral routes of administration may require higher doses of polynucleotide compared to more direct application to the nucleotide to diseased tissue, as do polynucleotides of increasing length. In one embodiment, human unit dose forms of T-cells comprise a suitable dosage range or effective amount that provides any therapeutic effect. As appreciated by one of ordinary skill in the art, a therapeutic effect depends on a number of factors. Dosages are generally selected by the physician or other health care professional in accordance with a variety of parameters known in the art, such as severity of symptoms, history of the patient and the like. A dose may be about 104 cells to about 108 cells, about 106 cells to about 108 cells, about 108 to about 1011 cells, or about 108 to about 5 x 1010 cells. A dose may also about 106 cells/im 2 to about 1010 cells/im 2 , or about 106 cells/m 2 to about 108 cells/m 2 . Proteins(s) of the invention, and/or nucleic acids encoding the protein(s), can also be administered via liposomes, which may also serve to: 1) target the proteins(s) to a particular tissue, such as lymphoid tissue; 2) to target selectively to diseases cells; or, 3) to increase the half-life of the peptide composition. Liposomes include emulsions, foams, micelles, insoluble monolayers, liquid crystals, phospholipid dispersions, lamellar layers and the like. In these preparations, the peptide to be delivered is incorporated as part of a liposome, alone or in conjunction with a molecule which binds to a receptor prevalent among lymphoid cells, such as monoclonal antibodies which bind to the CD45 antigen, or with other WO 2004/098515 PCT/US2004/013568 64 therapeutic or immunogenic compositions. Thus, liposomes either filled or decorated with a desired peptide of the invention can be directed to the site of lymphoid cells, where the liposomes then deliver the peptide compositions. Liposomes for use in accordance with the invention are formed from standard vesicle-forming lipids, which generally include neutral and negatively charged phospholipids and a sterol, such as cholesterol. The selection of lipids is generally guided by consideration of, e.g., liposome size, acid lability and stability of the liposomes in the blood stream. A variety of methods are available for preparing liposomes, as described in, e.g., Szoka, et al., Ann. Rev. Biophys. Bioeng. 9:467 (1980), and U.S. Patent Nos. 4,235,871, 4,501,728, 4,837,028, and 5,019,369. For targeting cells of the immune system, a ligand to be incorporated into the liposome can include, e.g., antibodies or fragments thereof specific for cell surface determinants of the desired immune system cells. A liposome suspension containing a peptide may be administered intravenously, locally, topically, etc. in a dose which varies according to, inter alia, the manner of administration, the peptide being delivered, and the stage of the disease being treated. For solid compositions, conventional nontoxic solid carriers may be used which include, for example, pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharin, talcum, cellulose, glucose, sucrose, magnesium carbonate, and the like. For oral administration, a pharmaceutically acceptable nontoxic composition is formed by incorporating any of the normally employed excipients, such as those carriers previously listed, and generally 10 95% of active Ingredient, that is, one or more peptides of the invention, and more preferably at a concentration of 25%-75%. For aerosol administration, immunogenic peptides are preferably supplied in finely divided form along with a surfactant and propellant. Typical percentages of peptides are about 0.01%-20% by weight, preferably about 1%-10%. The surfactant must, of course, be nontoxic, and preferably soluble in the propellant. Representative of such agents are the esters or partial esters of fatty acids containing from about 6 to 22 carbon atoms, such as caproic, octanoic, lauric, palmitic, stearic, linoleic, linolenic, olesteric and oleic acids with an aliphatic polyhydric alcohol or its cyclic anhydride. Mixed esters, such as mixed or natural glycerides may be employed. The surfactant may constitute about 0.1 %-20% by weight of the composition, preferably about 0.25-5%. The balance of the composition is ordinarily propellant. A carrier can also be included, as desired, as with, e.g., lecithin for intranasal delivery. Xi) Diagnostic and Prognostic Embodiments of 109P1 D4. As disclosed herein, 109P1 D4 polynucleotides, polypeptides, reactive cytotoxic T cells (CTL), reactive helper T cells (HTL) and anti-polypeptide antibodies are used in well known diagnostic, prognostic and therapeutic assays that examine conditions associated with dysregulated cell growth such as cancer, in particular the cancers listed in Table I (see, e.g., both its specific pattern of tissue expression as well as its overexpression in certain cancers as described for example in the Example entitled "Expression analysis of 109P1 D4 in normal tissues, and patient specimens"). 1 09P1 D4 can be analogized to a prostate associated antigen PSA, the archetypal marker that has been used by medical practitioners for years to identify and monitor the presence of prostate cancer (see, e.g., Merrill et al., J. Urol. 163(2): 503-5120 (2000); Polascik et al., J. Urol. Aug; 162(2):293-306 (1999) and Fortier et aL., J. Nat. Cancer Inst. 91(19): 1635 1640(1999)). A variety of other diagnostic markers are also used in similar contexts including p53 and K-ras (see, e.g., Tulchinsky et aL., Int J Mol Med 1999 Jul 4(1):99-102 and Minimoto et aL., Cancer Detect Prev 2000;24(1):1-12). Therefore, this disclosure of 109P1D4 polynucleotides and polypeptides (as well as 109P1D4 polynucleotide probes and anti-1 09P1 D4 antibodies used to identify the presence of these molecules) and their properties allows skilled artisans to utilize these molecules in methods that are analogous to those used, for example, in a variety of diagnostic assays directed to examining conditions associated with cancer. Typical embodiments of diagnostic methods which utilize the 109P1 D4 polynucleotides, polypeptides, reactive T WO 2004/098515 PCT/US2004/013568 65 cells and antibodies are analogous to those methods from well-established diagnostic assays, which employ, e.g., PSA polynucleotides, polypeptides, reactive T cells and antibodies. For example, just as PSA polynucleotides are used as probes (for example in Northern analysis, see, e.g., Sharief et al., Biochem. Mol. Biol. Int. 33(3):567-74(1994)) and primers (for example in PCR analysis, see, e.g., Okegawa et aL., J. Urol. 163(4): 1189-1190 (2000)) to observe the presence and/or the level of PSA mRNAs in methods of monitoring PSA overexpression or the metastasis of prostate cancers, the 109P1 D4 polynucleotides described herein can be utilized in the same way to detect 109P1 D4 overexpression or the metastasis of prostate and other cancers expressing this gene. Alternatively, just as PSA polypeptides are used to generate antibodies specific for PSA which can then be used to observe the presence and/or the level of PSA proteins in methods to monitor PSA protein overexpression (see, e.g., Stephan et al., Urology 55(4):560-3 (2000)) or the metastasis of prostate cells (see, e.g., Alanen et al., Pathol. Res. Pract. 192(3):233-7 (1996)), the 109P1D4 polypeptides described herein can be utilized to generate antibodies for use in detecting 109P1D4 overexpression or the metastasis of prostate cells and cells of other cancers expressing this gene. Specifically, because metastases involves the movement of cancer cells from an organ of origin (such as the lung or prostate gland etc.) to a different area of the body (such as a lymph node), assays which examine a biological sample for the presence of cells expressing 109P1 D4 polynucleotides and/or polypeptides can be used to provide evidence of metastasis. For example, when a biological sample from tissue that does not normally contain 109P1 D4-expressing cells (lymph node) is found to contain 109P1 D4-expressing cells such as the 109P1 D4 expression seen in LAPC4 and LAPC9, xenografts isolated from lymph node and bone metastasis, respectively, this finding is indicative of metastasis. Alternatively 109P1D4 polynucleotides and/or polypeptides can be used to provide evidence of cancer, for example, when cells in a biological sample that do not normally express 109P1 D4 or express 109P1 D4 at a different level are found to express 109P11D4 or have an increased expression of 109P1D4 (see, e.g., the 109P1D4 expression in the cancers listed in Table I and in patient samples etc. shown in the accompanying Figures). In such assays, artisans may further wish to generate supplementary evidence of metastasis by testing the biological sample for the presence of a second tissue restricted marker (in addition to 109P1D4) such as PSA, PSCA etc. (see, e.g., Alanen et aL, Pathol. Res. Pract. 192(3): 233 237 (1996)). The use of immunohistochemistry to identify the presence of a 109P1D4 polypeptide within a tissue section can indicate an altered state of certain cells within that tissue. It is well understood in the art that the ability of an antibody to localize to a polypeptide that is expressed in cancer cells is a way of diagnosing presence of disease, disease stage, progression and/or tumor aggressiveness. Such an antibody can also detect an altered distribution of the polypeptide within the cancer cells, as compared to corresponding non-malignant tissue. The 109P1D4 polypeptide and immunogenic compositions are also useful in view of the phenomena of altered subcellular protein localization in disease states. Alteration of cells from normal to diseased state causes changes in cellular morphology and is often associated with changes in subcellular protein localization/distribution. For example, cell membrane proteins that are expressed in a polarized manner in normal cells can be altered in disease, resulting in distribution of the protein in a non-polar manner over the whole cell surface. The phenomenon of altered subcellular protein localization in a disease state has been demonstrated with MUCI and Her2 protein expression by use of immunohistochemical means. Normal epithelial cells have a typical apical distribution of MUC1, in addition to some supranuclear localization of the glycoprotein, whereas malignant lesions often demonstrate an apolar staining pattern (Diaz et al, The Breast Journal, 7; 40-45 (2001); Zhang et al, Clinical Cancer Research, 4; 2669-2676 (1998): Cao, et al, The Journal of Histochemistry and Cytochemistry, 45: 1547-1557 (1997)). In addition, normal breast epithelium is either negative for Her2 protein or exhibits only a basolateral distribution whereas malignant cells can express WO 2004/098515 PCT/US2004/013568 66 the protein over the whole cell surface (De Potter, et al, International Journal of Cancer, 44; 969-974 (1989): McCormick, et al, 117; 935-943 (2002)). Alternatively, distribution of the protein may be altered from a surface only localization to include diffuse cytoplasmic expression in the diseased state. Such an example can be seen with MUCI (Diaz, et a, The Breast Journal, 7: 40-45 (2001)). Alteration in the localization/distribution of a protein in the cell, as detected by immunohistochemical methods, can also provide valuable information concerning the favorability of certain treatment modalities. This last point is illustrated by a situation where a protein may be intracellular in normal tissue, but cell surface in malignant cells; the cell surface location makes the cells favorably amenable to antibody-based diagnostic and treatment regimens. When such an alteration of protein localization occurs for 109P1 D4, the 109P1 D4 protein and immune responses related thereto are very useful. Accordingly, the ability to determine whether alteration of subcellular protein localization occurred for 24P4C12 make the 109P1 D4 protein and immune responses related thereto very useful. Use of the 109P1 D4 compositions allows those skilled in the art to make important diagnostic and therapeutic decisions. Immunohistochemical reagents specific to 109P1D4 are also useful to detect metastases of tumors expressing 109P1D4 when the polypeptide appears in tissues where 109P1 D4 is not normally produced. Thus, 109P1 D4 polypeptides and antibodies resulting from immune responses thereto are useful in a variety of important contexts such as diagnostic, prognostic, preventative and/or therapeutic purposes known to those skilled in the art. Just as PSA polynucleotide fragments and polynucleotide variants are employed by skilled artisans for use in methods of monitoring PSA, 109P1D4 polynucleotide fragments and polynucleotide variants are used in an analogous manner. In particular, typical PSA polynucleotides used in methods of monitoring PSA are probes or primers which consist of fragments of the PSA cDNA sequence. Illustrating this, primers used to PCR amplify a PSA polynucleotide must include less than the whole PSA sequence to function in the polymerase chain reaction. In the context of such PCR reactions, skilled artisans generally create a variety of different polynucleotide fragments that can be used as primers in order to amplify different portions of a polynucleotide of interest or to optimize amplification reactions (see, e.g., Caetano-Anolles, G. Biotechniques 25(3): 472-476, 478-480 (1998); Robertson et aL., Methods Mol. Biol. 98:121-154 (1998)). An additional illustration of the use of such fragments is provided in the Example entitled "Expression analysis of 109P1 D4 in normal tissues, and patient specimens," where a 109P1D4 polynucleotide fragment is used as a probe to show the expression of 109P1D4 RNAs in cancer cells. In addition, variant polynucleotide sequences are typically used as primers and probes for the corresponding mRNAs in PCR and Northern analyses (see, e.g., Sawai et al., Fetal Diagn. Ther. 1996 Nov-Dec 11(6):407-13 and Current Protocols In Molecular Biology, Volume 2, Unit 2, Frederick M. Ausubel et aL. eds., 1995)). Polynucleotide fragments and variants are useful in this context where they are capable of binding to a target polynucleotide sequence (e.g., a 109P1D4 polynucleotide shown in Figure 2 or variant thereof) under conditions of high stringency. Furthermore, PSA polypeptides which contain an epitope that can be recognized by an antibody or T cell that specifically binds to that epitope are used in methods of monitoring PSA. 109P1 D4 polypeptide fragments and polypeptide analogs or variants can also be used in an analogous manner. This practice of using polypeptide fragments or polypeptide variants to generate antibodies (such as anti-PSA antibodies or T cells) is typical in the art with a wide variety of systems such as fusion proteins being used by practitioners (see, e.g., Current Protocols In Molecular Biology, Volume 2, Unit 16, Frederick M. Ausubel et aL. eds., 1995). In this context, each epitope(s) functions to provide the architecture with which an antibody or T cell is reactive. Typically, skilled artisans create a variety of different polypeptide fragments that can be used in order to generate immune responses specific for different portions of a polypeptide of interest (see, e.g., U.S. Patent No. 5,840,501 and U.S. Patent No. 5,939,533). For example it may be preferable to utilize a polypeptide comprising one of the 109P1D4 biological motifs discussed herein or a motif-bearing subsequence which is readily identified by one of skill in the WO 2004/098515 PCT/US2004/013568 67 art based on motifs available in the art. Polypeptide fragments, variants or analogs are typically useful in this context as long as they comprise an epitope capable of generating an antibody or T cell specific for a target polypeptide sequence (e.g. a 109P1D4 polypeptide shown in Figure 3). As shown herein, the 109P1D4 polynucleotides and polypeptides (as well as the 109P1D4 polynucleotide probes and anti-109P1D4 antibodies or T cells used to identify the presence of these molecules) exhibit specific properties that make them useful in diagnosing cancers such as those listed in Table I. Diagnostic assays that measure the presence of 109P1 D4 gene products, in order to evaluate the presence or onset of a disease condition described herein, such as prostate cancer, are used to identify patients for preventive measures or further monitoring, as has been done so successfully with PSA. Moreover, these materials satisfy a need in the art for molecules having similar or complementary characteristics to PSA in situations where, for example, a definite diagnosis of metastasis of prostatic origin cannot be made on the basis of a test for PSA alone (see, e.g., Alanen et al., Pathol. Res. Pract. 192(3): 233-237 (1996)), and consequently, materials such as 109P1D4 polynucleotides and polypeptides (as well as the 109P1D4 polynucleotide probes and anti 109P1 D4 antibodies used to identify the presence of these molecules) need to be employed to confirm a metastases of prostatic origin. Finally, in addition to their use in diagnostic assays, the 109P1 D4 polynucleotides disclosed herein have a number of other utilities such as their use in the identification of oncogenetic associated chromosomal abnormalities in the chromosomal region to which the 109P1 D4 gene maps (see the Example entitled "Chromosomal Mapping of 109P1 D4" below). Moreover, in addition to their use in diagnostic assays, the 109P1D4-related proteins and polynucleotides disclosed herein have other utilities such as their use in the forensic analysis of tissues of unknown origin (see, e.g., Takahama K Forensic Sci Int 1996 Jun 28;80(1-2): 63-9). Additionally, 109P1 D4-related proteins or polynucleotides of the invention can be used to treat a pathologic condition characterized by the over-expression of 109P1D4. For example, the amino acid or nucleic acid sequence of Figure 2 or Figure 3, or fragments of either, can be used to generate an immune response to a 109P1D4 antigen. Antibodies or other molecules that react with 109P1 D4 can be used to modulate the function of this molecule, and thereby provide a therapeutic benefit. XII.) Inhibition of 109P1D4 Protein Function The invention includes various methods and compositions for inhibiting the binding of 109P1 D4 to its binding partner or its association with other protein(s) as well as methods for inhibiting 109P1D4 function. XII.A.) Inhibition of 109P1D4 With ntracellular Antibodies In one approach, a recombinant vector that encodes single chain antibodies that specifically bind to 109P1 D4 are introduced into 109P1 D4 expressing cells via gene transfer technologies. Accordingly, the encoded single chain anti 109P1D4 antibody is expressed intracellularly, binds to 109P1D4 protein, and thereby inhibits its function. Methods for engineering such intracellular single chain antibodies are well known. Such intracellular antibodies, also known as "intrabodies", are specifically targeted to a particular compartment within the cell, providing control over where the inhibitory activity of the treatment is focused. This technology has been successfully applied in the art (for review, see Richardson and Marasco, 1995, TIBTECH vol. 13). Intrabodies have been shown to virtually eliminate the expression of otherwise abundant cell surface receptors (see, e.g., Richardson et aL., 1995, Proc. NatI. Acad. Sci. USA 92: 3137-3141; Beerli et aL., 1994, J. Biol. Chem. 289: 23931-23936; Deshane et al, 1994, Gene Ther. 1: 332-337). Single chain antibodies comprise the variable domains of the heavy and light chain joined by a flexible linker WO 2004/098515 PCT/US2004/013568 68 polypeptide, and are expressed as a single polypeptide. Optionally, single chain antibodies are expressed as a single chain variable region fragment joined to the light chain constant region. Well-known intracellular trafficking signals are engineered into recombinant polynucleotide vectors encoding such single chain antibodies in order to target precisely the intrabody to the desired intracellular compartment. For example, intrabodies targeted to the endoplasmic reticulum (ER) are engineered to incorporate a leader peptide and, optionally, a C-terminal ER retention signal, such as the KDEL amino acid motif. Intrabodies intended to exert activity in the nucleus are engineered to include a nuclear localization signal. Lipid moieties are joined to intrabodies in order to tether the intrabody to the cytosolic side of the plasma membrane. Intrabodies can also be targeted to exert function in the cytosol. For example, cytosolic intrabodies are used to sequester factors within the cytosol, thereby preventing them from being transported to their natural cellular destination. In one embodiment, intrabodies are used to capture 109P1D4 in the nucleus, thereby preventing its activity within the nucleus. Nuclear targeting signals are engineered into such 109P1D4 intrabodies in order to achieve the desired targeting. Such 109P1D4 intrabodies are designed to bind specifically to a particular 109P1D4 domain. In another embodiment, cytosolic intrabodies that specifically bind to a 109P1 D4 protein are used to prevent 109P1 D4 from gaining access to the nucleus, thereby preventing it from exerting any biological activity within the nucleus (e.g., preventing 109P1 D4 from forming transcription complexes with other factors). In order to specifically direct the expression of such intrabodies to particular cells, the transcription of the intrabody is placed under the regulatory control of an appropriate tumor-specific promoter and/or enhancer. In order to target intrabody expression specifically to prostate, for example, the PSA promoter and/or promoter/enhancer can be utilized (See, for example, U.S. Patent No. 5,919,652 issued 6 July 1999). XII.B.) Inhibition of 109P1 D4 with Recombinant Proteins In another approach, recombinant molecules bind to 109P1D4 and thereby inhibit 109P1D4 function. For example, these recombinant molecules prevent or inhibit 109P1 D4 from accessing/binding to its binding partner(s) or associating with other protein(s). Such recombinant molecules can, for example, contain the reactive part(s) of a 109P1 D4 specific antibody molecule. In a particular embodiment, the 109P1D4 binding domain of a 109P1D4 binding partner is engineered into a dimeric fusion protein, whereby the fusion protein comprises two 109P1 D4 ligand binding domains linked to the Fc portion of a human IgG, such as human IgG1. Such igG portion can contain, for example, the CH2 and CH 3 domains and the hinge region, but not the CHI domain. Such dimeric fusion proteins are administered in soluble form to patients suffering from a cancer associated with the expression of 109P1 D4, whereby the dimeric fusion protein specifically binds to 109P1 D4 and blocks 109P1 D4 interaction with a binding partner. Such dimeric fusion proteins are further combined into multimeric proteins using known antibody linking technologies. XII.C.) Inhibition of 109P1 D4 Transcription or Translation The present invention also comprises various methods and compositions for inhibiting the transcription of the 109P1 D4 gene. Similarly, the invention also provides methods and compositions for inhibiting the translation of 109P1 D4 mRNA into protein. In one approach, a method of inhibiting the transcription of the 109P1D4 gene comprises contacting the 109P1D4 gene with a 109P1D4 antisense polynucleotide, In another approach, a method of inhibiting 109P1 D4 mRNA translation comprises contacting a 109P1 D4 mRNA with an antisense polynucleotide. In another approach, a 109P1 D4 specific ribozyme is used to cleave a 109P1 D4 message, thereby inhibiting translation. Such antisense and ribozyme based methods can also be directed to the regulatory regions of the 109P1D4 gene, such as 109P1D4 promoter and/or enhancer WO 2004/098515 PCT/US2004/013568 69 elements. Similarly, proteins capable of inhibiting a 109P1D4 gene transcription factor are used to inhibit 109P1 D4 mRNA transcription. The various polynucleotides and compositions useful in the aforementioned methods have been described above. The use of antisense and ribozyme molecules to inhibit transcription and translation is well known in the art. Other factors that inhibit the transcription of 109P1 D4 by interfering with 109P1 D4 transcriptional activation are also useful to treat cancers expressing I 09P1 D4. Similarly, factors that interfere with 109P1 D4 processing are useful to treat cancers that express 109P104. Cancer treatment methods utilizing such factors are also within the scope of the invention. XILD.) General Considerations for Therapeutic Strategies Gene transfer and gene therapy technologies can be used to deliver therapeutic polynucleotide molecules to tumor cells synthesizing 109PID4 (i.e., antisense, ribozyme, polynucleotides encoding intrabodies and other 109P1D4 inhibitory molecules). A number of gene therapy approaches are known in the art. Recombinant vectors encoding 109P1 D4 antisense polynucleoides, ribozymes, factors capable of interfering with 109P1 D4 transcription, and so forth, can be delivered to target tumor cells using such gene therapy approaches. The above therapeutic approaches can be combined with any one of a wide variety of surgical, chemotherapy or radiation therapy regimens. The therapeutic approaches of the invention can enable the use of reduced dosages of chemotherapy (or other therapies) and/or less frequent administration, an advantage for all patients and particularly for those that do not tolerate the toxicity of the chemotherapeutic agent well. The anti-tumor activity of a particular composition (e.g., antisense, ribozyme, intrabody), or a combination of such compositions, can be evaluated using various in vitro and in vivo assay systems. In vitro assays that evaluate therapeutic activity include cell growth assays, soft agar assays and other assays indicative of tumor promoting activity, binding assays capable of determining the extent to which a therapeutic composition will inhibit the binding of 109P1 D4 to a binding partner, etc. In vivo, the effect of a 109P1D4 therapeutic composition can be evaluated in a suitable animal model. For example, xenogenic prostate cancer models can be used, wherein human prostate cancer explants or passaged xenograft tissues are introduced into immune compromised animals, such as nude or SCiD mice (Klein et aL, 1997, Nature Medicine 3: 402-408). For example, PCT Patent Application W098/16628 and U.S. Patent 6,107,540 describe various xenograft models of human prostate cancer capable of recapitulating the development of primary tumors, micrometastasis, and the formation of osteoblastic metastases characteristic of late stage disease. Efficacy can be predicted using assays that measure inhibition of tumor formation, tumor regression or metastasis, and the like. In vivo assays that evaluate the promotion of apoptosis are useful in evaluating therapeutic compositions. In one embodiment, xenografts from tumor bearing mice treated with the therapeutic composition can be examined for the presence of apoptotic foci and compared to untreated control xenograft-bearing mice. The extent to which apoptotic foci are found in the tumors of the treated mice provides an indication of the therapeutic efficacy of the composition. The therapeutic compositions used in the practice of the foregoing methods can be formulated into pharmaceutical compositions comprising a carrier suitable for the desired delivery method. Suitable carriers include any material that when combined with the therapeutic composition retains the anti-tumor function of the therapeutic composition and is generally non-reactive with the patient's immune system. Examples include, but are not limited to, any of a number of standard pharmaceutical carriers such as sterile phosphate buffered saline solutions, bacteriostatic water, and the like (see, generally, Remington's Pharmaceutical Sciences 16th Edition, A. Osal., Ed., 1980). Therapeutic formulations can be solubilized and administered via any route capable of delivering the therapeutic composition to the tumor site. Potentially effective routes of administration include, but are not limited to, intravenous, parenteral, intraperitoneal, intramuscular, intratumor, intradermal, intraorgan, orthotopic, and the like. A preferred WO 2004/098515 PCT/US2004/013568 70 formulation for intravenous injection comprises the therapeutic composition in a solution of preserved bacteriostatic water, sterile unpreserved water, and/or diluted in polyvinylchloride or polyethylene bags containing 0.9% sterile Sodium Chloride for Injection, USP. Therapeutic protein preparations can be lyophilized and stored as sterile powders, preferably under vacuum, and then reconstituted in bacteriostatic water (containing for example, benzyl alcohol preservative) or in sterile water prior to injection. Dosages and administration protocols for the treatment of cancers using the foregoing methods will vary with the method and the target cancer, and will generally depend on a number of other factors appreciated in the art. XIll.) Identification, Characterization and Use of Modulators of 109P1D4 Methods to Identify and Use Modulators In one embodiment, screening is performed to identify modulators that induce or suppress a particular expression profile, suppress or induce specific pathways, preferably generating the associated phenotype thereby. In another embodiment, having identified differentially expressed genes important in a particular state; screens are performed to identify modulators that alter expression of individual genes, either increase or decrease. In another embodiment, screening is performed to identify modulators that alter a biological function of the expression product of a differentially expressed gene. Again, having identified the importance of a gene in a particular state, screens are performed to identify agents that bind and/or modulate the biological activity of the gene product. In addition, screens are done for genes that are induced in response to a candidate agent. After identifying a modulator (one that suppresses a cancer expression pattern leading to a normal expression pattern, or a modulator of a cancer gene that leads to expression of the gene as in normal tissue) a screen is performed to identify genes that are specifically modulated in response to the agent. Comparing expression profiles between normal tissue and agent-treated cancer tissue reveals genes that are not expressed in normal tissue or cancer tissue, but are expressed in agent treated tissue, and vice versa. These agent-specific sequences are identified and used by methods described herein for cancer genes or proteins. In particular these sequences and the proteins they encode are used in marking or identifying agent treated cells. In addition, antibodies are raised against the agent-induced proteins and used to target novel therapeutics to the treated cancer tissue sample. Modulator-related Identification and Screening Assays: Gene Expression-related Assays Proteins, nucleic acids, and antibodies of the invention are used in screening assays. The cancer-associated proteins, antibodies, nucleic acids, modified proteins and cells containing these sequences are used in screening assays, such as evaluating the effect of drug candidates on a "gene expression profile," expression profile of polypeptides or alteration of biological function. In one embodiment, the expression profiles are used, preferably in conjunction with high throughput screening techniques to allow monitoring for expression profile genes after treatment with a candidate agent (e.g., Davis, GF, et al, J Biol Screen 7:69 (2002); Zlokarnik, et al., Science 279:84-8 (1998); Heid, Genome Res 6:986 94,1996). The cancer proteins, antibodies, nucleic acids, modified proteins and cells containing the native or modified cancer proteins or genes are used in screening assays. That is, the present invention comprises methods for screening for compositions which modulate the cancer phenotype or a physiological function of a cancer protein of the invention. This is done on a gene itself or by evaluating the effect of drug candidates on a "gene expression profile" or biological function. In one embodiment, expression profiles are used, preferably in conjunction with high throughput screening techniques to allow WO 2004/098515 PCT/US2004/013568 71 monitoring after treatment with a candidate agent, see Zlokamik, supra. A variety of assays are executed directed to the genes and proteins of the invention. Assays are run on an individual nucleic acid or protein level. That is, having identified a particular gene as up regulated in cancer, test compounds are screened for the ability to modulate gene expression or for binding to the cancer protein of the invention. "Modulation" in this context includes an increase or a decrease in gene expression. The preferred amount of modulation will depend on the original change of the gene expression in normal versus tissue undergoing cancer, with changes of at least 10%, preferably 50%, more preferably 100-300%, and in some embodiments 300-1000% or greater. Thus, if a gene exhibits a 4-fold increase in cancer tissue compared to normal tissue, a decrease of about four-fold is often desired; similarly, a 10-fold decrease in cancer tissue compared to normal tissue a target value of a 10-fold increase in expression by the test compound is often desired. Modulators that exacerbate the type of gene expression seen in cancer are also useful, e.g., as an upregulated target in further analyses. The amount of gene expression is monitored using nucleic acid probes and the quantification of gene expression levels, or, alternatively, a gene product itself is monitored, e.g., through the use of antibodies to the cancer protein and standard immunoassays. Proteomics and separation techniques also allow for quantification of expression. Expression Monitoring to Identify Compounds that Modify Gene Expression In one embodiment, gene expression monitoring, i.e., an expression profile, is monitored simultaneously for a number of entities. Such profiles will typically involve one or more of the genes of Figure 2. In this embodiment, e.g., cancer nucleic acid probes are attached to biochips to detect and quantify cancer sequences in a particular cell. Alternatively, PCR can be used. Thus, a series, e.g., wells of a microtiter plate, can be used with dispensed primers in desired wells. A PCR reaction can then be performed and analyzed for each well. Expression monitoring is performed to identify compounds that modify the expression of one or more cancer associated sequences, e.g., a polynucleotide sequence set out in Figure 2. Generally, a test modulator is added to the cells prior to analysis. Moreover, screens are also provided to identify agents that modulate cancer, modulate cancer proteins of the invention, bind to a cancer protein of the invention, or interfere with the binding of a cancer protein of the invention and an antibody or other binding partner. In one embodiment, high throughput screening methods involve providing a library containing a large number of potential therapeutic compounds (candidate compounds). Such "combinatorial chemical libraries" are then screened in one or more assays to identify those library members (particular chemical species or subclasses) that display a desired characteristic activity. The compounds thus identified can serve as conventional "lead compounds," as compounds for screening, or as therapeutics, In certain embodiments, combinatorial libraries of potential modulators are screened for an ability to bind to a cancer polypeptide or to modulate activity. Conventionally, new chemical entities with useful properties are generated by identifying a chemical compound (called a "lead compound") with some desirable property or activity, e.g., inhibiting activity, creating variants of the lead compound, and evaluating the property and activity of those variant compounds. Often, high throughput screening (HTS) methods are employed for such an analysis. As noted above, gene expression monitoring is conveniently used to test candidate modulators (e.g., protein, nucleic acid or small molecule). After the candidate agent has been added and the cells allowed to incubate for a period, the sample containing a target sequence to be analyzed is, e.g., added to a biochip. If required, the target sequence is prepared using known techniques. For example, a sample is treated to lyse the cells, using known lysis buffers, electroporation, etc., with purification and/or amplification such as PCR performed as appropriate. For example, an in vitro transcription with labels covalently attached to the nucleotides is performed. Generally, WO 2004/098515 PCT/US2004/013568 72 the nucleic acids are labeled with biotin-FITC or PE, or with cy3 or cy5. The target sequence can be labeled with, e.g., a fluorescent, a chemiluminescent, a chemical, or a radioactive signal, to provide a means of detecting the target sequence's specific binding to a probe. The label also can be an enzyme, such as alkaline phosphatase or horseradish peroxidase, which when provided with an appropriate substrate produces a product that is detected. Alternatively, the label is a labeled compound or small molecule, such as an enzyme inhibitor, that binds but is not catalyzed or altered by the enzyme. The label also can be a moiety or compound, such as, an epitope tag or biotin which specifically binds to streptavidin. For the example of biotin, the streptavidin is labeled as described above, thereby, providing a detectable signal for the bound target sequence. Unbound labeled streptavidin is typically removed prior to analysis. As will be appreciated by those in the art, these assays can be direct hybridization assays or can comprise "sandwich assays", which include the use of multiple probes, as is generally outlined in U.S. Patent Nos, 5, 681,702; 5,597,909; 5,545,730; 5,594,117; 5,591,584; 5,571,670; 5,580,731; 5,571,670; 5,591,584; 5,624,802; 5,635,352; 5,594,118; 5,359,100; 5,124, 246; and 5,681,697. In this embodiment, in general, the target nucleic acid is prepared as outlined above, and then added to the biochip comprising a plurality of nucleic acid probes, under conditions that allow the formation of a hybridization complex. A variety of hybridization conditions are used in the present invention, including high, moderate and low stringency conditions as outlined above. The assays are generally run under stringency conditions which allow formation of the label probe hybridization complex only in the presence of target. Stringency can be controlled by altering a step parameter that is a thermodynamic variable, including, but not limited to, temperature, formamide concentration, salt concentration, chaotropic salt concentration pH, organic solvent concentration, etc. These parameters may also be used to control non-specific binding, as is generally outlined in U.S. Patent No. 5,681,697. Thus, it can be desirable to perform certain steps at higher stringency conditions to reduce non-specific binding. The reactions outlined herein can be accomplished in a variety of ways. Components of the reaction can be added simultaneously, or sequentially, in different orders, with preferred embodiments outlined below. In addition, the reaction may include a variety of other reagents. These include salts, buffers, neutral proteins, e.g. albumin, detergents, etc. which can be used to facilitate optimal hybridization and detection, and/or reduce nonspecific or background interactions. Reagents that otherwise improve the efficiency of the assay, such as protease inhibitors, nuclease inhibitors, anti-microbial agents, etc., may also be used as appropriate, depending on the sample preparation methods and purity of the target. The assay data are analyzed to determine the expression levels of individual genes, and changes in expression levels as between states, forming a gene expression profile. Biological Activity-related Assays The invention provides methods identify or screen for a compound that modulates the activity of a cancer-related gene or protein of the invention. The methods comprise adding a test compound, as defined above, to a cell comprising a cancer protein of the invention. The cells contain a recombinant nucleic acid that encodes a cancer protein of the invention. In another embodiment, a library of candidate agents is tested on a plurality of cells. In one aspect, the assays are evaluated in the presence or absence or previous or subsequent exposure of physiological signals, e.g. hormones, antibodies, peptides, antigens, cytokines, growth factors, action potentials, pharmacological agents including chemotherapeutics, radiation, carcinogenics, or other cells (i.e., cell-cell contacts). In another example, the determinations are made at different stages of the cell cycle process. In this way, compounds that modulate genes or proteins of the invention are identified. Compounds with pharmacological activity are able to enhance or WO 2004/098515 PCT/US2004/013568 73 interfere with the activity of the cancer protein of the invention. Once identified, similar structures are evaluated to identify critical structural features of the compound. In one embodiment, a method of modulating ( e.g., inhibiting) cancer cell division is provided; the method comprises administration of a cancer modulator. In another embodiment, a method of modulating ( e.g., inhibiting) cancer is provided; the method comprises administration of a cancer modulator. In a further embodiment, methods of treating cells or individuals with cancer are provided; the method comprises administration of a cancer modulator. In one embodiment, a method for modulating the status of a cell that expresses a gene of the invention is provided. As used herein status comprises such art-accepted parameters such as growth, proliferation, survival, function, apoptosis, senescence, location, enzymatic activity, signal transduction, etc. of a cell. In one embodiment, a cancer inhibitor is an antibody as discussed above. In another embodiment, the cancer inhibitor is an antisense molecule. A variety of cell growth, proliferation, and metastasis assays are known to those of skill in the art, as described herein. High Throughput Screening to Identify Modulators The assays to identify suitable modulators are amenable to high throughput screening. Preferred assays thus detect enhancement or inhibition of cancer gene transcription, inhibition or enhancement of polypeptide expression, and inhibition or enhancement of polypeptide activity. In one embodiment, modulators evaluated in high throughput screening methods are proteins, often naturally occurring proteins or fragments of naturally occurring proteins. Thus, e.g., cellular extracts containing proteins, or random or directed digests of proteinaceous cellular extracts, are used. In this way, libraries of proteins are made for screening in the methods of the invention. Particularly preferred in this embodiment are libraries of bacterial, fungal, viral, and mammalian proteins, with the latter being preferred, and human proteins being especially preferred. Particularly useful test compound will be directed to the class of proteins to which the target belongs, e.g., substrates for enzymes, or ligands and receptors. Use of Soft Aqar Growth and Colony Formation to Identify and Characterize Modulators Normal cells require a solid substrate to attach and grow. When cells are transformed, they lose this phenotype and grow detached from the substrate. For example, transformed cells can grow in stirred suspension culture or suspended in semi-solid media, such as semi-solid or soft agar. The transformed cells, when transfected with tumor suppressor genes, can regenerate normal phenotype and once again require a solid substrate to attach to and grow. Soft agar growth or colony formation in assays are used to identify modulators of cancer sequences, which when expressed in host cells, inhibit abnormal cellular proliferation and transformation. A modulator reduces or eliminates the host cells' ability to grow suspended in solid or semisolid media, such as agar. Techniques for soft agar growth or colony formation in suspension assays are described in Freshney, Culture of Animal Cells a Manual of Basic Technique (3rd ed., 1994). See also, the methods section of Garkavtsev et al. (1996), supra. Evaluation of Contact Inhibition and Growth Density Limitation to Identify and Characterize Modulators Normal cells typically grow in a flat and organized pattern in cell culture until they touch other cells. When the cells touch one another, they are contact inhibited and stop growing. Transformed cells, however, are not contact inhibited and continue to grow to high densities in disorganized foci. Thus, transformed cells grow to a higher saturation density than corresponding normal cells. This is detected morphologically by the formation of a disoriented monolayer of cells or cells in foci. Alternatively, labeling index with ( 3 H)-thymidine at saturation density is used to measure density limitation of growth, similarly an MTT or Alamar blue assay will reveal proliferation capacity of cells and the the ability of modulators to affect same. See Freshney (1994), supra. Transformed cells, when transfected with tumor suppressor genes, can regenerate a normal phenotype and become contact inhibited and would grow to a lower density.

WO 2004/098515 PCT/US2004/013568 74 In this assay, labeling index with 3 H)-thymidine at saturation density is a preferred method of measuring density limitation of growth. Transformed host cells are transfected with a cancer-associated sequence and are grown for 24 hours at saturation density in non-limiting medium conditions. The percentage of cells labeling with ( 3 H)-thymidine is determined by incorporated cpm. Contact independent growth is used to identify modulators of cancer sequences, which had led to abnormal cellular proliferation and transformation. A modulator reduces or eliminates contact independent growth, and returns the cells to a normal phenotype. Evaluation of Growth Factor or Serum Dependence to Identify and Characterize Modulators Transformed cells have lower serum dependence than their normal counterparts (see, e.g., Temin, J. Natl. Cancer Inst. 37:167-175 (1966); Eagle et al., J. Exp. Med 131:836-879 (1970)); Freshney, supra. This is in part due to release of various growth factors by the transformed cells. The degree of growth factor or serum dependence of transformed host cells can be compared with that of control. For example, growth factor or serum dependence of a cell is monitored in methods to identify and characterize compounds that modulate cancer-associated sequences of the invention. Use of Tumor-specific Marker Levels to Identify and Characterize Modulators Tumor cells release an increased amount of certain factors (hereinafter "tumor specific markers") than their normal counterparts. For example, plasminogen activator (PA) is released from human glioma at a higher level than from normal brain cells (see, e.g., Gullino, Angiogenesis, Tumor Vascularization, and Potential Interference with Tumor Growth, in Biological Responses in Cancer, pp. 178-184 (Mihich (ed.) 1985)). Similarly, Tumor Angiogenesis Factor (TAF) is released at a higher level in tumor cells than their normal counterparts. See, e.g., Folkman, Angiogenesis and Cancer, Sem Cancer Biol. (1992)), while bFGF is released from endothelial tumors (Ensoli, B et al). Various techniques which measure the release of these factors are described in Freshney (1994), supra. Also, see, Unkless et al., J. Biol. Chem. 249:4295-4305 (1974); Strickland & Beers, J. Biol. Chem. 251:5694-5702 (1976); Whur et al., Br. J. Cancer 42:305 312 (1980); Gullino, Angiogenesis, Tumor Vascularization, and Potential Interference with Tumor Growth, in Biological Responses in Cancer, pp. 178-184 (Mihich (ed.) 1985); Freshney, Anticancer Res. 5:111-130 (1985). For example, tumor specific marker levels are monitored in methods to identify and characterize compounds that modulate cancer-associated sequences of the invention, Invasiveness into Matrigel to Identify and Characterize Modulators The degree of invasiveness into Matrigel or an extracellular matrix constituent can be used as an assay to identify and characterize compounds that modulate cancer associated sequences. Tumor cells exhibit a positive correlation between malignancy and invasiveness of cells into Matrigel or some other extracellular matrix constituent. In this assay, tumorigenic cells are typically used as host cells. Expression of a tumor suppressor gene in these host cells would decrease invasiveness of the host cells. Techniques described in Cancer Res. 1999; 59:6010; Freshney (1994), supra, can be used. Briefly, the level of invasion of host cells is measured by using filters coated with Matrigel or some other extracellular matrix constituent. Penetration into the gel, or through to the distal side of the filter, is rated as invasiveness, and rated histologically by number of cells and distance moved, or by prelabeling the cells with 1211 and counting the radioactivity on the distal side of the filter or bottom of the dish. See, e.g., Freshney (1984), supra. Evaluation of Tumor Growth In Vivo to Identify and Characterize Modulators Effects of cancer-associated sequences on cell growth are tested in transgenic or immune-suppressed organisms. Transgenic organisms are prepared in a variety of art-accepted ways. For example, knock-out transgenic organisms, e.g., mammals such as mice, are made, in which a cancer gene is disrupted or in which a cancer gene is inserted. Knock-out transgenic mice are made by insertion of a marker gene or other heterologous gene into the endogenous cancer gene site in WO 2004/098515 PCT/US2004/013568 75 the mouse genome via homologous recombination. Such mice can also be made by substituting the endogenous cancer gene with a mutated version of the cancer gene, or by mutating the endogenous cancer gene, e.g., by exposure to carcinogens. To prepare transgenic chimeric animals, e.g., mice, a DNA construct is introduced into the nuclei of embryonic stem cells. Cells containing the newly engineered genetic lesion are injected into a host mouse embryo, which is re implanted into a recipient female. Some of these embryos develop into chimeric mice that possess germ cells some of which are derived from the mutant cell line. Therefore, by breeding the chimeric mice it is possible to obtain a new line of mice containing the introduced genetic lesion (see, e.g., Capecchi et al., Science 244:1288 (1989)). Chimeric mice can be derived according to US Patent 6,365,797, issued 2 April 2002; US Patent 6,107,540 issued 22 August 2000; Hogan et al., Manipulating the Mouse Embryo: A laboratory Manual, Cold Spring Harbor Laboratory (1988) and Teratocarcinomas and Embryonic Stem Cells: A Practical Approach, Robertson, ed., IRL Press, Washington, D.C., (1987). Alternatively, various immune-suppressed or immune-deficient host animals can be used. For example, a genetically athymic "nude" mouse (see, e.g., Giovanella et al., J. Nati. Cancer Inst. 52:921 (1974)), a SCID mouse, a thymectornized mouse, or an irradiated mouse (see, e.g., Bradley et al., Br. J. Cancer 38:263 (1978); Selby et al., Br. J. Cancer 41:52 (1980)) can be used as a host. Transplantable tumor cells (typically about 106 cells) injected into isogenic hosts produce invasive tumors in a high proportion of cases, while normal cells of similar origin will not. In hosts which developed invasive tumors, cells expressing cancer-associated sequences are injected subcutaneously or orthotopically. Mice are then separated into groups, including control groups and treated experimental groups) e.g. treated with a modulator). After a suitable length of time, preferably 4-8 weeks, tumor growth is measured (e.g., by volume or by its two largest dimensions, or weight) and compared to the control. Tumors that have statistically significant reduction (using, e.g., Student's T test) are said to have inhibited growth. In Vitro Assays to Identify and Characterize Modulators Assays to identify compounds with modulating activity can be performed in vitro. For example, a cancer polypeptide is first contacted with a potential modulator and incubated for a suitable amount of time, e.g., from 0.5 to 48 hours. In one embodiment, the cancer polypeptide levels are determined in vitro by measuring the level of protein or mRNA. The level of protein is measured using immunoassays such as Western blotting, ELISA and the like with an antibody that selectively binds to the cancer polypeptide or a fragment thereof. For measurement of mRNA, amplification, e.g., using PCR, LCR, or hybridization assays, e. g., Northern hybridization, RNAse protection, dot blotting, are preferred. The level of protein or mRNA is detected using directly or indirectly labeled detection agents, e.g., fluorescently or radioactively labeled nucleic acids, radioactively or enzymatically labeled antibodies, and the like, as described herein. Alternatively, a reporter gene system can be devised using a cancer protein promoter operably linked to a reporter gene such as luciferase, green fluorescent protein, CAT, or P-gal. The reporter construct is typically transfected into a cell. After treatment with a potential modulator, the amount of reporter gene transcription, translation, or activity is measured according to standard techniques known to those of skill in the art (Davis GF, supra; Gonzalez, J. & Negulescu, P. Curr. Opin. Biotechnol. 1998: 9:624). As outlined above, in vitro screens are done on individual genes and gene products. That is, having identified a particular differentially expressed gene as important in a particular state, screening of modulators of the expression of the gene or the gene product itself is performed, In one embodiment, screening for modulators of expression of specific gene(s) is performed. Typically, the expression of only one or a few genes is evaluated. In another embodiment, screens are designed to first find compounds WO 2004/098515 PCT/US2004/013568 76 that bind to differentially expressed proteins. These compounds are then evaluated for the ability to modulate differentially expressed activity. Moreover, once initial candidate compounds are identified, variants can be further screened to better evaluate structure activity relationships. Binding Assays to Identify and Characterize Modulators In binding assays in accordance with the invention, a purified or isolated gene product of the invention is generally used. For example, antibodies are generated to a protein of the invention, and immunoassays are run to determine the amount and/or location of protein. Alternatively, cells comprising the cancer proteins are used in the assays. Thus, the methods comprise combining a cancer protein of the invention and a candidate compound such as a ligand, and determining the binding of the compound to the cancer protein of the invention. Preferred embodiments utilize the human cancer protein; animal models of human disease of can also be developed and used. Also, other analogous mammalian proteins also can be used as appreciated by those of skill in the art. Moreover, in some embodiments variant or derivative cancer proteins are used. Generally, the cancer protein of the invention, or the ligand, is non-diffusibly bound to an insoluble support. The support can, e.g., be one having isolated sample receiving areas (a microtiter plate, an array, etc.). The insoluble supports can be made of any composition to which the compositions can be bound, is readily separated from soluble material, and is otherwise compatible with the overall method of screening. The surface of such supports can be solid or porous and of any convenient shape. Examples of suitable insoluble supports include microtiter plates, arrays, membranes and beads, These are typically made of glass, plastic (e.g., polystyrene), polysaccharide, nylon, nitrocellulose, or TeflonTM, etc. Microtiter plates and arrays are especially convenient because a large number of assays can be carried out simultaneously, using small amounts of reagents and samples. The particular manner of binding of the composition to the support is not crucial so long as it is compatible with the reagents and overall methods of the invention, maintains the activity of the composition and is nondiffusable. Preferred methods of binding include the use of antibodies which do not sterically block either the ligand binding site or activation sequence when attaching the protein to the support, direct binding to "sticky" or ionic supports, chemical crosslinking, the synthesis of the protein or agent on the surface, etc. Following binding of the protein or ligand/binding agent to the support, excess unbound material is removed by washing. The sample receiving areas may then be blocked through incubation with bovine serum albumin (BSA), casein or other innocuous protein or other moiety. Once a cancer protein of the invention is bound to the support, and a test compound is added to the assay. Alternatively, the candidate binding agent is bound to the support and the cancer protein of the invention is then added. Binding agents include specific antibodies, non-natural binding agents identified in screens of chemical libraries, peptide analogs, etc. Of particular interest are assays to identify agents that have a low toxicity for human cells. A wide variety of assays can be used for this purpose, including proliferation assays, cAMP assays, labeled in vitro protein-protein binding assays, electrophoretic mobility shift assays, immunoassays for protein binding, functional assays (phosphorylation assays, etc.) and the like. A determination of binding of the test compound (ligand, binding agent, modulator, etc.) to a cancer protein of the invention can be done in a number of ways. The test compound can be labeled, and binding determined directly, e.g., by attaching all or a portion of the cancer protein of the invention to a solid support, adding a labeled candidate compound (e.g., a fluorescent label), washing off excess reagent, and determining whether the label is present on the solid support. Various blocking and washing steps can be utilized as appropriate.

WO 2004/098515 PCT/US2004/013568 77 In certain embodiments, only one of the components is labeled, e.g., a protein of the invention or ligands labeled. Alternatively, more than one component is labeled with different labels, e.g., 1125, for the proteins and a fluorophor for the compound. Proximity reagents, e.g., quenching or energy transfer reagents are also useful. Competitive Binding to Identify and Characterize Modulators In one embodiment, the binding of the "test compound" is determined by competitive binding assay with a "competitor." The competitor is a binding moiety that binds to the target molecule (e.g., a cancer protein of the invention). Competitors include compounds such as antibodies, peptides, binding partners, ligands, etc. Under certain circumstances, the competitive binding between the test compound and the competitor displaces the test compound. In one embodiment, the test compound is labeled. Either the test compound, the competitor, or both, is added to the protein for a time sufficient to allow binding. Incubations are performed at a temperature that facilitates optimal activity, typically between four and 40 0 C. Incubation periods are typically optimized, e.g., to facilitate rapid high throughput screening; typically between zero and one hour wili be sufficient. Excess reagent is generally removed or washed away. The second component is then added, and the presence or absence of the labeled component is followed, to indicate binding. In one embodiment, the competitor is added first, followed by the test compound. Displacement of the competitor is an indication that the test compound is binding to the cancer protein and thus is capable of binding to, and potentially modulating, the activity of the cancer protein. In this embodiment, either component can be labeled. Thus, e.g., if the competitor is labeled, the presence of label in the post-test compound wash solution indicates displacement by the test compound. Alternatively, if the test compound is labeled, the presence of the label on the support indicates displacement. In an alternative embodiment, the test compound is added first, with incubation and washing, followed by the competitor. The absence of binding by the competitor indicates that the test compound binds to the cancer protein with higher affinity than the competitor. Thus, if the test compound is labeled, the presence of the label on the support, coupled with a lack of competitor binding, indicates that the test compound binds to and thus potentially modulates the cancer protein of the invention. Accordingly, the competitive binding methods comprise differential screening to identity agents that are capable of modulating the activity of the cancer proteins of the invention. In this embodiment, the methods comprise combining a cancer protein and a competitor in a first sample. A second sample comprises a test compound, the cancer protein, and a competitor. The binding of the competitor is determined for both samples, and a change, or difference in binding between the two samples indicates the presence of an agent capable of binding to the cancer protein and potentially modulating its activity. That is, if the binding of the competitor is different in the second sample relative to the first sample, the agent is capable of binding to the cancer protein. Alternatively, differential screening is used to identify drug candidates that bind to the native cancer protein, but cannot bind to modified cancer proteins. For example the structure of the cancer protein is modeled and used in rational drug design to synthesize agents that interact with that site, agents which generally do not bind to site-modified proteins. Moreover, such drug candidates that affect the activity of a native cancer protein are also identified by screening drugs for the ability to either enhance or reduce the activity of such proteins. Positive controls and negative controls can be used in the assays. Preferably control and test samples are performed in at least triplicate to obtain statistically significant results. Incubation of all samples occurs for a time sufficient to allow for the binding of the agent to the protein. Following incubation, samples are washed free of non-specifically bound material and the amount of bound, generally labeled agent determined. For example, where a radiolabel is employed, the samples can be counted in a scintillation counter to determine the amount of bound compound.

WO 2004/098515 PCT/US2004/013568 78 A variety of other reagents can be included in the screening assays. These include reagents like salts, neutral proteins, e.g. albumin, detergents, etc. which are used to facilitate optimal protein-protein binding and/or reduce non-specific or background interactions. Also reagents that otherwise improve the efficiency of the assay, such as protease inhibitors, nuclease inhibitors, anti-microbial agents, etc., can be used. The mixture of components is added in an order that provides for the requisite binding. Use of Polynucleotides to Down-regulate or Inhibit a Protein of the Invention. Polynucleotide modulators of cancer can be introduced into a cell containing the target nucleotide sequence by formation of a conjugate with a ligand-binding molecule, as described in WO 91/04753. Suitable ligand-binding molecules include, but are not limited to, cell surface receptors, growth factors, other cytokines, or other ligands that bind to cell surface receptors. Preferably, conjugation of the ligand binding molecule does not substantially interfere with the ability of the ligand binding molecule to bind to its corresponding molecule or receptor, or block entry of the sense or antisense oligonucleotide or its conjugated version into the cell. Alternatively, a polynucleotide modulator of cancer can be introduced into a cell containing the target nucleic acid sequence, e.g., by formation of a polynucleotide-lipid complex, as described in WO 90/10448. It is understood that the use of antisense molecules or knock out and knock in models may also be used in screening assays as discussed above, in addition to methods of treatment. Inhibitory and Antisense Nucleotides In certain embodiments, the activity of a cancer-associated protein is down-regulated, or entirely inhibited, by the use of antisense polynucleotide or inhibitory small nuclear RNA (snRNA), i.e., a nucleic acid complementary to, and which can preferably hybridize specifically to, a coding mRNA nucleic acid sequence, e.g., a cancer protein of the invention, mRNA, or a subsequence thereof. Binding of the antisense polynucleotide to the mRNA reduces the translation and/or stability of the mRNA. In the context of this invention, antisense polynucleotides can comprise naturally occurring nucleotides, or synthetic species formed from naturally occurring subunits or their close homologs. Antisense polynucleotides may also have altered sugar moieties or inter-sugar linkages. Exemplary among these are the phosphorothioate and other sulfur containing species which are known for use in the art. Analogs are comprised by this invention so long as they function effectively to hybridize with nucleotides of the invention. See, e.g., Isis Pharmaceuticals, Carlsbad, CA; Sequitor, Inc., Natick, MA. Such antisense polynucleotides can readily be synthesized using recombinant means, or can be synthesized in vitro. Equipment for such synthesis is sold by several vendors, including Applied Biosystems. The preparation of other oligonucleotides such as phosphorothioates and alkylated derivatives is also well known to those of skill in the art. Antisense molecules as used herein include antisense or sense oligonucleotides. Sense oligonucleotides can, e.g., be employed to block transcription by binding to the anti-sense strand. The antisense and sense oligonucleotide comprise a single stranded nucleic acid sequence (either RNA or DNA) capable of binding to target mRNA (sense) or DNA (antisense) sequences for cancer molecules. Antisense or sense oligonucleotides, according to the present invention, comprise a fragment generally at least about 12 nucleotides, preferably from about 12 to 30 nucleotides. The ability to derive an antisense or a sense oligonucleotide, based upon a cDNA sequence encoding a given protein is described in, e.g., Stein &Cohen (Cancer Res. 48:2659 (1988 and van der Krol et al. (BioTechniques 6:958 (1988)). Ribozymes In addition to antisense polynucleotides, ribozymes can be used to target and inhibit transcription of cancer associated nucleotide sequences. A ribozyme is an RNA molecule that catalytically cleaves other RNA molecules. Different WO 2004/098515 PCT/US2004/013568 79 kinds of ribozymes have been described, including group I ribozymes, hammerhead ribozymes, hairpin ribozymes, RNase P, and axhead ribozymes (see, e.g., Castanotto et al., Adv. in Pharmacology 25: 289-317 (1994) for a general review of the properties of different ribozymes). The general features of hairpin ribozymes are described, e.g., in Hampel et al., Nucl. Acids Res. 18:299-304 (1990); European Patent Publication No. 0360257; U.S. Patent No. 5,254,678. Methods of preparing are well known to those of skill in the art (see, e.g., WO 94/26877; Ojwang et al., Proc. Nati. Acad. Sci. USA 90:6340-6344 (1993); Yamada et al., Human Gene Therapy 1:39-45 (1994); Leavitt et al., Proc. NatI. Acad Sci. USA 92:699- 703 (1995); Leavitt et al., Human Gene Therapy 5:1151-120 (1994); and Yamada et al., Virology 205:121-126 (1994)). Use of Modulators in Phenotypic Screening In one embodiment, a test compound is administered to a population of cancer cells, which have an associated cancer expression profile. By "administration" or "contacting" herein is meant that the modulator is added to the cells in such a manner as to allow the modulator to act upon the cell, whether by uptake and intracellular action, or by action at the cell surface. In some embodiments, a nucleic acid encoding a proteinaceous agent (i.e., a peptide) is put into a viral construct such as an adenoviral or retroviral construct, and added to the cell, such that expression of the peptide agent is accomplished, e.g., PCT US97/01019. Regulatable gene therapy systems can also be used. Once the modulator has been administered to the cells, the cells are washed if desired and are allowed to incubate under preferably physiological conditions for some period. The cells are then harvested and a new gene expression profile is generated. Thus, e.g., cancer tissue is screened for agents that modulate, e.g., induce or suppress, the cancer phenotype. A change in at least one gene, preferably many, of the expression profile indicates that the agent has an effect on cancer activity. Similarly, altering a biological function or a signaling pathway is indicative of modulator activity. By defining such a signature for the cancer phenotype, screens for new drugs that alter the phenotype are devised. With this approach, the drug target need not be known and need not be represented In the original gene/protein expression screening platform, nor does the level of transcript for the target protein need to change. The modulator inhibiting function will serve as a surrogate marker As outlined above, screens are done to assess genes or gene products. That is, having identified a particular differentially expressed gene as important in a particular state, screening of modulators of either the expression of the gene or the gene product itself is performed. Use of Modulators to Affect Peptides of the Invention Measurements of cancer polypeptide activity, or of the cancer phenotype are performed using a variety of assays. For example, the effects of modulators upon the function of a cancer polypeptide(s) are measured by examining parameters described above. A physiological change that affects activity is used to assess the influence of a test compound on the polypeptides of this invention. When the functional outcomes are determined using intact cells or animals, a variety of effects can be assesses such as, in the case of a cancer associated with solid tumors, tumor growth, tumor metastasis, neovascularization, hormone release, transcriptional changes to both known and uncharacterized genetic markers (e.g., by Northern blots), changes in cell metabolism such as cell growth or pH changes, and changes in intracellular second messengers such as cGNIP. Methods of Identifying Characterizing Cancer-associated Sequences Expression of various gene sequences is correlated with cancer. Accordingly, disorders based on mutant or variant cancer genes are determined. In one embodiment, the invention provides methods for identifying cells containing WO 2004/098515 PCT/US2004/013568 80 variant cancer genes, e.g., determining the presence of, all or part, the sequence of at least one endogenous cancer gene in a cell. This is accomplished using any number of sequencing techniques. The invention comprises methods of identifying the cancer genotype of an individual, e.g., determining all or part of the sequence of at least one gene of the invention in the individual. This is generally done in at least one tissue of the individual, e.g., a tissue set forth in Table 1, and may include the evaluation of a number of tissues or different samples of the same tissue. The method may include comparing the sequence of the sequenced gene to a known cancer gene, i.e., a wild-type gene to determine the presence of family members, homologies, mutations or variants. The sequence of all or part of the gene can then be compared to the sequence of a known cancer gene to determine if any differences exist. This is done using any number of known homology programs, such as BLAST, Bestfit, etc. The presence of a difference in the sequence between the cancer gene of the patient and the known cancer gene correlates with a disease state or a propensity for a disease state, as outlined herein. In a preferred embodiment, the cancer genes are used as probes to determine the number of copies of the cancer gene in the genome. The cancer genes are used as probes to determine the chromosomal localization of the cancer genes, Information such as chromosomal localization finds use in providing a diagnosis or prognosis in particular when chromosomal abnormalities such as translocations, and the like are identified in the cancer gene locus. XIV.) Kits/Articles of Manufacture For use in the laboratory, prognostic, prophylactic, diagnostic and therapeutic applications described herein, kits are within the scope of the invention. Such kits can comprise a carrier, package, or container that is compartmentalized to receive one or more containers such as vials, tubes, and the like, each of the container(s) comprising one of the separate elements to be used in the method, along with a label or insert comprising instructions for use, such as a use described herein. For example, the container(s) can comprise a probe that is or can be detectably labeled. Such probe can be an antibody or polynucleotide specific for a protein or a gene or message of the invention, respectively. Where the method utilizes nucleic acid hybridization to detect the target nucleic acid, the kit can also have containers containing nucleotide(s) for amplification of the target nucleic acid sequence. Kits can comprise a container comprising a reporter, such as a biotin binding protein, such as avidin or streptavidin, bound to a reporter molecule, such as an enzymatic, fluorescent, or radioisotope label; such a reporter can be used with, e.g., a nucleic acid or antibody. The kit can include all or part of the amino acid sequences in Figure 2 or Figure 3 or analogs thereof, or a nucleic acid molecule that encodes such amino acid sequences. The kit of the invention will typically comprise the container described above and one or more other containers associated therewith that comprise materials desirable from a commercial and user standpoint, including buffers, diluents, filters, needles, syringes; carrier, package, container, vial and/or tube labels listing contents and/or instructions for use, and package inserts with instructions for use. A label can be present on or with the container to indicate that the composition is used for a specific therapy or non therapeutic application, such as a prognostic, prophylactic, diagnostic or laboratory application, and can also indicate directions for either in vivo or in vitro use, such as those described herein. Directions and or other information can also be included on an insert(s) or label(s) which is included with or on the kit. The label can be on or associated with the container. A label a can be on a container when letters, numbers or other characters forming the label are molded or etched into the container itself; a label can be associated with a container when it is present within a receptacle or carrier that also holds the container, e.g., as a package insert. The label can indicate that the composition is used for diagnosing, treating, prophylaxing or prognosing a condition, such as a neoplasia of a tissue set forth in Table i. The terms "kit" and "article of manufacture" can be used as synonyms.

WO 2004/098515 PCT/US2004/013568 81 In another embodiment of the invention, an article(s) of manufacture containing compositions, such as amino acid sequence(s), small molecule(s), nucleic acid sequence(s), and/or antibody(s), e.g., materials useful for the diagnosis, prognosis, prophylaxis and/or treatment of neoplasias of tissues such as those set forth in Table I is provided. The article of manufacture typically comprises at least one container and at least one label. Suitable containers include, for example, bottles, vials, syringes, and test tubes. The containers can be formed from a variety of materials such as glass, metal or plastic. The container can hold amino acid sequence(s), small molecule(s), nucleic acid sequence(s), cell population(s) and/or antibody(s). In one embodiment, the container holds a polynucleotide for use in examining the mRNA expression profile of a cell, together with reagents used for this purpose. In another embodiment a container comprises an antibody, binding fragment thereof or specific binding protein for use in evaluating protein expression of1 09P1 D4 in cells and tissues, or for relevant laboratory, prognostic, diagnostic, prophylactic and therapeutic purposes; indications and/or directions for such uses can be included on or with such container, as can reagents and other compositions or tools used for these purposes. In another embodiment, a container comprises materials for eliciting a cellular or humoral immune response, together with associated indications and/or directions. In another embodiment, a container comprises materials for adoptive immunotherapy, such as cytotoxic T cells (CTL) or helper T cells (HTL), together with associated indications and/or directions; reagents and other compositions or tools used for such purpose can also be included. The container can alternatively hold a composition that is effective for treating, diagnosis, prognosing or prophylaxing a condition and can have a sterile access port (for example the container can be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic injection needle). The active agents in the composition can be an antibody capable of specifically binding 109P1 D4 and modulating the function of I 09P1 D4. The article of manufacture can further comprise a second container comprising a pharmaceutically-acceptable buffer, such as phosphate-buffered saline, Ringer's solution and/or dextrose solution. It can further include other materials desirable from a commercial and user standpoint, including other buffers, diluents, filters, stirrers, needles, syringes, and/or package inserts with indications and/or instructions for use. EXAMPLES: Various aspects of the invention are further described and illustrated by way of the several examples that follow, none of which is intended to limit the scope of the invention. Example 1: SSH-Generated Isolation of cDNA Fragment of the 109P1 D4 Gene To isolate genes that are over-expressed in prostate cancer we used the Suppression Subtractive Hybridization (SSH) procedure using cDNA derived from prostate cancer tissues. The 1 09P1 D4 SSH cDNA sequence was from an experiment where cDNA derived from LNCaP cells that was androgen-deprived (by growing in the presence of charcoal-stripped serum) was subtracted from cDNA derived from LNCaP cells that were stimulated with mibolerone for 9 hours. Materials and Methods Human Tissues: The patient cancer and normal tissues were purchased from different sources such as the NDRI (Philadelphia, PA). mRNA for some normal tissues were purchased from different companies such as Clontech, Palo Alto, CA. RNA Isolation: Tissues were homogenized in Trizol reagent (Life Technologies, Gibco BRL) using 10 ml/ g tissue to isolate total RNA. Poly A RNA was purified from total RNA using Qiagen's Oligotex mRNA Mini and Midi kits. Total and mRNA were quantified by spectrophotometric analysis (O.D. 260/280 nm) and analyzed by gel electrophoresis.

WO 2004/098515 PCT/US2004/013568 82 Oligonucleotides: The following HPLC purified oligonucleotides were used. DPNCDN (cDNA synthesis primer): 5'TTTTGATCAAGCTT3o3' (SEQ ID NO: 44) Adaptor 1: 5'CTAATACGACTCACTATAGGGCTCGAGCGGCCGCCCGGGCAG3' (SEQ ID NO: 45) 3'GGCCCGTCCTAG5' (SEQ ID NO: 46) Adaptor 2: 5'GTAATACGACTCACTATAGGGCAGCGTGGTCGCGGCCGAG3' (SEQ ID NO: 47) 3'CGGCTCCTAG5' (SEQ ID NO: 48) PCR primer 1: 5'CTAATACGACTCACTATAGGGC3' (SEQ ID NO: 49) Nested primer (NP)1: 5'TCGAGCGGCCGCCCGGGCAGGA3' (SEQ ID NO: 50) Nested primer (NP)2: 5'AGCGTGGTCGCGGCCGAGGA3' (SEQ ID NO: 51) Suppression Subtractive Hybridization: Suppression Subtractive Hybridization (SSH) was used to identify cDNAs corresponding to genes that may be differentially expressed in prostate cancer. The SSH reaction utilized cDNA from LNCaP prostate cancer cells. The 109P1D4 SSH sequence was derived from cDNA subtraction of LNCaP stimulated with mibolerone minus LNCaP in the absence of androgen. The SSH DNA sequence (Figure 1) was identified. The cDNA derived from androgen-deprived LNCaP cells was used as the source of the "driver" cDNA, while the cDNA from androgen-stimulated LNCaP cells was used as the source of the "tester" cDNA. Double stranded cDNAs corresponding to tester and driver cDNAs were synthesized from 2 pg of poly(A)+ RNA isolated from the relevant xenograft tissue, as described above, using CLONTECH's PCR-Select cDNA Subtraction Kit and I pg of oligonucleotide DPNCDN as primer. First- and second strand synthesis were carried out as described in the Kit's user manual protocol (CLONTECH Protocol No. PTI 117-1, Catalog No. K1804-1). The resulting cDNA was digested with Dpn I for 3 hrs at 37oC. Digested cDNA was extracted with phenol/chloroform (1:1) and ethanol precipitated. Tester cDNA was generated by diluting I ipl of Dpn Il digested cDNA from the relevant tissue source (see above) (400 ng) in 5 pl of water. The diluted cDNA (2 pI, 160 ng) was then ligated to 2 pl of Adaptor 1 and Adaptor 2 (10 pM), in separate ligation reactions, in a total volume of 10 [d at 160C overnight, using 400 pi of T4 DNA ligase (CLONTECH). Ligation was terminated with 1 VI of 0.2 M EDTA and heating at 72oC for 5 min. The first hybridization was performed by adding 1.5 l (600 ng) of driver cDNA to each of two tubes containing 1.5 p1 (20 ng) Adaptor 1- and Adaptor 2- ligated tester cDNA. In a final volume of 4 pl, the samples were overlaid with mineral oil, denatured in an MJ Research thermal cycler at 980C for 1.5 minutes, and then were allowed to hybridize for 8 hrs at 68oC. The two hybridizations were then mixed together with an additional 1 pl of fresh denatured driver cDNA and were allowed to hybridize overnight at 68C. The second hybridization was then diluted in 200 pLi of 20 mM Hepes, pH 8.3, 50 mM NaCi, 0.2 mM EDTA, heated at 700C for 7 min. and stored at -20oC. PCR Amplification, Cloning and Seguencing of Gene Fragments Generated from SSH: WO 2004/098515 PCT/US2004/013568 83 To amplify gene fragments resulting from SSH reactions, two PCR amplifications were performed. In the primary PCR reaction 1 pl of the diluted final hybridization mix was added to 1 p1 of PCR primer 1 (10 pM), 0.5 pl dNTP mix (10 pM), 2.5 pl 10 x reaction buffer (CLONTECH) and 0.5 Al 50 x Advantage cDNA polymerase Mix (CLONTECH) in a final volume of 25 RI. PCR 1 was conducted using the following conditions: 750C for 5 min., 940C for 25 sec., then 27 cycles of 940C for 10 sec, 660C for 30 sec, 7200 for 1.5 min. Five separate primary PCR reactions were performed for each experiment. The products were pooled and diluted 1:10 with water. For the secondary PCR reaction, 1 pl from the pooled and diluted primary PCR reaction was added to the same reaction mix as used for PCR 1, except that primers NP1 and NP2 (10 pM) were used instead of PCR primer 1. PCR 2 was performed using 10-12 cycles of 9400 for 10 sec, 680C for 30 sec, and 7200 for 1.5 minutes. The PCR products were analyzed using 2% agarose gel electrophoresis. The PCR products were inserted into pCR2.1 using the T/A vector cloning kit (Invitrogen). Transformed E. coli were subjected to blue/white and ampicillin selection. White colonies were picked and arrayed into 96 well plates and were grown in liquid culture overnight. To identify inserts, PCR amplification was performed on 1 pl of bacterial culture using the conditions of PCRI and NP1 and NP2 as primers. PCR products were analyzed using 2% agarose gel electrophoresis. Bacterial clones were stored in 20% glycerol in a 96 well format, Plasmid DNA was prepared, sequenced, and subjected to nucleic acid homology searches of the GenBank, dBest, and NCI-CGAP databases. RT-PCR Expression Analysis: First strand cDNAs can be generated from 1 pg of mRNA with oligo (dT)12-18 priming using the Gibco-BRL Superscript Preamplification system. The manufacturer's protocol was used which included an incubation for 50 min at 420C with reverse transcriptase followed by RNAse H treatment at 370C for 20 min. After completing the reaction, the volume can be increased to 200 Al with water prior to normalization. First strand cDNAs from 16 different normal human tissues can be obtained from Clontech. Normalization of the first strand cDNAs from multiple tissues was performed by using the primers 5'ATATCGCCGCGCTCGTCGTCGACAA3' (SEQ ID NO: 52) and 5'AGCCAOACGCAGCTCATTGTAGAAGG 3' (SEQ ID NO: 53) to amplify P-actin. First strand cDNAs (5 pI) were amplified in a total volume of 50 [d containing 0.4 pM primers, 0.2 pM each dNTPs, 1X PCR buffer (Clontech, 10 mM Tris-HCL, 1.5 mM MgCl2, 50 mM KCI, pH8.3) and IX Klentaq DNA polymerase (Clontech). Five pl of the PCR reaction can be removed at 18, 20, and 22 cycles and used for agarose gel electrophoresis. PCR was performed using an MJ Research thermal cycler under the following conditions: Initial denaturation can be at 940C for 15 sec, followed by a 18, 20, and 22 cycles of 940C for 15, 650C for 2 min, 720C for 5 sec. A final extension at 720C was carried out for 2 min. After agarose gel electrophoresis, the band intensities of the 283 base pair p-actin bands from multiple tissues were compared by visual inspection. Dilution factors for the first strand cDNAs were calculated to result in equal p-actin band intensities in all tissues after 22 cycles of PCR. Three rounds of normalization can be required to achieve equal band intensities in all tissues after 22 cycles of PCR. To determine expression levels of the 109P1 D4 gene, 5 pl of normalized first strand cDNA were analyzed by PCR using 26, and 30 cycles of amplification. Semi-quantitative expression analysis can be achieved by comparing the PCR products at cycle numbers that give light band intensities. The primers used for RT-PCR were designed using the 109P1D4 SSH sequence and are listed below: 109P1D4.1 5'- TGGTCTTTCAGGTAATTGCTGTTG - 3(SEQ ID NO: 54) 109P1 D4.2 5'- CTCCATCAATGTTATGTTGCCTGT -3' (SEQ ID NO: 55) WO 2004/098515 PCT/US2004/013568 84 A typical RT-PCR expression analysis is shown in Figure 15. Example 2: Isolation of Full Length 109P1D4 encoding DNA The 109P1D4 SSH sequence of 192 bp (Figure 1) exhibited homology to protocadherin 11 (PCDH1 1), a cell adhesion molecule related to the calcium dependent cadherins. The human cDNA sequence encodes a 1021 amino acid protein with an N terminal leader sequence and a transmembrane domain. 109P1 D4 v.1 of 4603bp was cloned from human prostate cancer xenograft LAPC-9AD cDNA library, revealing an ORF of 1021 amino acids (Figure 2 and Figure 3). Other variants (Transcript and SNP) of 109P1D4 were also identified and these are listed sequentially in Figure 2 and Figure 3. Example 3: Chromosomal Mapping of 109P1D4 Chromosomal localization can implicate genes in disease pathogenesis. Several chromosome mapping approaches are available including fluorescent in situ hybridization (FISH), human/hamster radiation hybrid (RH) panels (Walter et al., 1994; Nature Genetics 7:22; Research Genetics, Huntsville Al), human-rodent somatic cell hybrid panels such as is available from the Coriell Institute (Camden, New Jersey), and genomic viewers utilizing BLAST homologies to sequenced and mapped genomic clones (NCBI, Bethesda, Maryland). 109P1 D4 maps to chromosome Xq21.3 using 109P1 D4 sequence and the NCBI BLAST tool: located on the World Wide Web at: (.ncbinlm.nih.gov/genome/seq/page.cgi?F=HsBlast.html&&ORG=Hs). 109P1D4 was also identified on chromosome Ypl 1.2, a region of 99% identity to Xq21. Example 4: Expression Analysis of 109P1D4 in Normal Tissues and Patient Specimens Expression analysis by RT-PCR and Northern analysis demonstrated that normal tissue expression of a gene of Figure 2 is restricted predominantly to the tissues set forth in Table 1. Therapeutic applications for a gene of Figure 2 include use as a small molecule therapy and/or a vaccine (T cell or antibody) target. Diagnostic applications for a gene of Figure 2 include use as a diagnostic marker for local and/or metastasized disease. The restricted expression of a gene of Figure 2 in normal tissues makes it useful as a tumor target for diagnosis and therapy. Expression analysis of a gene of Figure 2 provides information useful for predicting susceptibility to advanced stage disease, rate of progression, and/or tumor aggressiveness. Expression status of a gene of Figure 2 in patient samples, tissue arrays and/or cell lines may be analyzed by: (i) immunohistochemical analysis; (ii) in situ hybridization; (iii) RT-PCR analysis on laser capture micro-dissected samples; (iv) Western blot analysis; and (v) Northern analysis. RT-PCR analysis and Northern blotting were used to evaluate gene expression in a selection of normal and cancerous urological tissues. The results are summarized in Figures 15-19. Figure 14 shows expression of 109P1 D4 in lymphoma cancer patient specimens. RNA was extracted from peripheral blood lymphocytes, cord blood isolated from normal individuals, and from lymphoma patient cancer specimens. Northern blots with I Opg of total RNA were probed with the 1 09P1 D4 sequence. Size standards in kilobases are on the side. Results show expression of 109P1 D4 in lymphoma patient specimens but not in the normal blood cells tested. Figure 15 shows expression of 109P1 D4 by RT-PCR. First strand cDNA was prepared from vital pool 1 (liver, lung and kidney), vital pool 2 (pancreas, colon and stomach), prostate cancer pool, bladder cancer pool, kidney cancer pool, colon cancer pool, lung cancer pool, ovary cancer pool, breast cancer pool, cancer metastasis pool, and pancreas cancer pool. Normalization was performed by PCR using primers to actin and GAPDH. Semi-quantitative PCR, using primers to 109P1 D4, was performed at 30 cycles of amplification. Results show strong expression of 109P1D4 in all cancer pools WO 2004/098515 PCT/US2004/013568 85 tested. Very low expression was detected in the vital pools. Figure 16 shows expression of 1 09P1 D4 in normal tissues. Two multiple tissue northern blots (Clontech), both with 2 pg of mRNAllane, were probed with the 109P1D4 SSH fragment. Size standards in kilobases (kb) are indicated on the side. Results show expression of approximately 10 kb 109P1 D4 transcript in ovary. Weak expression was also detected in placenta and brain, but not in the other normal tissues tested. Figure 17 shows expression of 109P1 D4 in human cancer cell lines. RNA was extracted from a number of human prostate and bone cancer cell lines. Northern blots with 10 pg of total RNAllane were probed with the 109P1D4 SSH fragment. Size standards in kilobases (kb) are indicated on the side. Results show expression of 109P1 D4 in LAPC-9AD, LAPC-9AI, LNCaP prostate cancer cell lines, and in the bone cancer cell lines, SK-ES-1 and RD-ES. Extensive expression of 109P1 D4 in normal tissues is shown in Figure 18A. A cDNA dot blot containing 76 different samples from human tissues was analyzed using a I 09P1 D4 SSH probe. Expression was only detected in multiple areas of the brain, placenta, ovary, and fetal brain, amongst all tissues tested. Figure 18B shows expression of 109P1D4 in patient cancer specimens. Expression of 109P1D4 was assayed in a panel of human cancers (T) and their respective matched normal tissues (N) on RNA dot blots. Upregulated expression of 109P1D4 in tumors compared to normal tissues was observed in uterus, lung and stomach. The expression detected in normal adjacent tissues (isolated from diseased tissues) but not in normal tissues (isolated from healthy donors) may indicate that these tissues are not fully normal and that 109P1D4 may be expressed in early stage tumors. Figure 19 shows 109P1D4 expression in lung cancer patient specimens. RNA was extracted from normal lung, prostate cancer xenograft LAPC-9AD, bone cancer cell line RD-ES, and lung cancer patient tumors. Northern blots with 10 pg of total RNA were probed with 109P1D4. Size standards in kilobases are on the side. Results show strong expression of 109P1D4 in lung tumor tissues as well as the RD-ES cell line, but not in normal lung. The restricted expression of 109P1 D4 in normal tissues and the expression detected in cancer patient specimens suggest that 109P1 D4 is a potential therapeutic target and a diagnostic marker for human cancers. Example 5: Splice Variants of 109P1 D4 Transcript variants are variants of mature mRNA from the same gene which arise by alternative transcription or alternative splicing. Alternative transcripts are transcripts from the same gene but start transcription at different points. Splice variants are mRNA variants spliced differently from the same transcript, In eukaryotes, when a multi-exon gene is transcribed from genomic DNA, the initial RNA is spliced to produce functional mRNA, which has only exons and is used for translation into an amino acid sequence. Accordingly, a given gene can have zero to many alternative transcripts and each transcript can have zero to many splice variants. Each transcript variant has a unique exon makeup, and can have different coding and/or non-coding (5' or 3' end) portions, from the original transcript. Transcript variants can code for similar or different proteins with the same or a similar function or can encode proteins with different functions, and can be expressed in the same tissue at the same time, or in different tissues at the same time, or in the same tissue at different times, or in different tissues at different times. Proteins encoded by transcript variants can have similar or different cellular or extracellular localizations, e.g., secreted versus intracellular. Transcript variants are identified by a variety of art-accepted methods. For example, alternative transcripts and splice variants are identified by full-length cloning experiment, or by use of full-length transcript and EST sequences. First, all human ESTs were grouped into clusters which show direct or indirect identity with each other. Second, ESTs in the same cluster were further grouped into sub-clusters and assembled into a consensus sequence. The original gene sequence is compared to the consensus sequence(s) or other full-length sequences. Each consensus sequence is a potential splice WO 2004/098515 PCT/US2004/013568 86 variant for that gene. Even when a variant is identified that is not a full-length clone, that portion of the variant is very useful for antigen generation and for further cloning of the full-length splice variant, using techniques known in the art. Moreover, computer programs are available in the art that identify transcript variants based on genomic sequences. Genomic-based transcript variant identification programs include FgenesH (A. Salamov and V. Solovyev, "Ab initio gene finding in Drosophila genomic DNA," Genome Research. 2000 April;10(4):516-22); Grail (URL compbio.ornl.gov/Grail-bin/EmptyGrailForm) and GenScan (URL genes.mit.edu/GENSCAN.html). For a general discussion of splice variant identification protocols see., e.g., Southan, C., A genomic perspective on human proteases, FEBS Lett. 2001 Jun 8; 498(2-3):214-8; de Souza, S.J., et al., Identification of human chromosome 22 transcribed sequences with ORF expressed sequence tags, Proc. Natl Acad Sci U S A. 2000 Nov 7; 97(23):12690-3. To further confirm the parameters of a transcript variant, a variety of techniques are available in the art, such as full-length cloning, proteomic validation, PCR-based validation, and 5' RACE validation, etc. (see e.g., Proteomic Validation: Brennan, S.O., et al., Albumin banks peninsula: a new termination variant characterized by electrospray mass spectrometry, Biochem Biophys Acta. 1999 Aug 17;1433(1-2):321-6; Ferranti P, et al,, Differential splicing of pre-messenger RNA produces multiple forms of mature caprine alpha(si)-casein, Eur J Biochem. 1997 Oct 1;249(1):1-7. For PCR-based Validation: Wellmann S, et al., Specific reverse transcription-PCR quantification of vascular endothelial growth factor (VEGF) splice variants by LightCycler technology, Clin Chem. 2001 Apr;47(4):654-60; Jia, H.P., et al., Discovery of new human beta defensins using a genomics-based approach, Gene. 2001 Jan 24; 263(1-2):211-8. For PCR-based and 5' RACE Validation: Brigle, K.E., et al., Organization of the murine reduced folate carrier gene and identification of variant splice forms, Biochem Biophys Acta. 1997 Aug 7; 1353(2): 191-8). It is known in the art that genomic regions are modulated in cancers. When the genomic region to which a gene maps is modulated in a particular cancer, the alternative transcripts or splice variants of the gene are modulated as well. Disclosed herein is that 109P1 D4 has a particular expression profile related to cancer. Alternative transcripts and splice variants of 109P1D4 may also be involved in cancers in the same or different tissues, thus serving as tumor-associated markers/antigens. Using the full-length gene and EST sequences, 8 transcript variants were identified, designated as 109P1D4 v.2, v.3, v.4, v.5, v.6, v.7, v.8 and v.9. The boundaries of the exon in the original transcript, 109P1D4 v.1, were shown in Table LI. Compared with 109P1 D4 v.1, transcript variant 109P1 D4 v.3 has spliced out 2069-2395 from variant 109P1 D4 v.1, as shown in Figure 12. Variant 109P1D4 v.4 spliced out 1162-2096 of variant 109P1D4 v.1. Variant 109P1D4 v.5 added one exon to the 5' and extended 2 bp to the 5' end and 288 bp to the 3' end of variant 109P1D4 v.1. Theoretically, each different combination of exons in spatial order, e.g. exon I of v.5 and exons I and 2 of v.3 or v.4, is a potential splice variant. Tables LII through LV are set forth on a variant-by-variant basis. Tables Lll(a)-(h) show nucleotide sequence of the transcript variants. Tables LIII(a)-(h) show the alignment of the transcript variants with nucleic acid sequence of 109P1D4 v.1. Tables LIV(a)-(h) lay out amino acid translation of the transcript variants for the identified reading frame orientation. Tables LV(a)-(h) displays alignments of the amino acid sequence encoded by the splice variants with that of 109P1D4 v.1. Example 6: Single Nucleotide Polymorphisms of 109P1D4 A Single Nucleotide Polymorphism (SNP) is a single base pair variation in a nucleotide sequence at a specific location. At any given point of the genome, there are four possible nucleotide base pairs: AlT, CIG, GIC and T/A. Genotype refers to the specific base pair sequence of one or more locations in the genome of an individual. Haplotype refers to the base pair sequence of more than one location on the same DNA molecule (or the same chromosome in higher organisms), WO 2004/098515 PCT/US2004/013568 87 often in the context of one gene or in the context of several tightly linked genes. SNP that occurs on a cDNA is called cSNP. This cSNP may change amino acids of the protein encoded by the gene and thus change the functions of the protein. Some SNP cause inherited diseases; others contribute to quantitative variations in phenotype and reactions to environmental factors including diet and drugs among individuals. Therefore, SNP and/or combinations of alleges (called haplotypes) have many applications, including diagnosis of inherited diseases, determination of drug reactions and dosage, identification of genes responsible for diseases, and analysis of the genetic relationship between individuals (P. Nowotny, J. M. Kwon and A. M. Goate, " SNP analysis to dissect human traits," Curr. Opin. Neurobiol. 2001 Oct; 11(5):637-641; M. Pirmohamed and B. K. Park, "Genetic susceptibility to adverse drug reactions," Trends Pharmacol. Sci. 2001 Jun; 22(6):298-305; J. H. Riley, C. J. Allan, E. Lai and A. Roses, "The use of single nucleotide polymorphisms in the isolation of common disease genes," Pharmacogenomics. 2000 Feb; 1(1):39-47; R. Judson, J. C. Stephens and A. Windemuth, "The predictive power of haplotypes in clinical response," Pharmacogenomics. 2000 Feb; 1(1): 15-26). SNP are identified by a variety of art-accepted methods (P. Bean, "The promising voyage of SNP target discovery," Am. Clin. Lab. 2001 Oct-Nov; 20(9):18-20; K. M. Weiss, "In search of human variation," Genome Res. 1998 Jul; 8(7):691 697; M. M. She, "Enabling large-scale pharmacogenetic studies by high-throughput mutation detection and genotyping technologies," Clin. Chem. 2001 Feb; 47(2):164-172). For example, SNP can be identified by sequencing DNA fragments that show polymorphism by gel-based methods such as restriction fragment length polymorphism (RFLP) and denaturing gradient gel electrophoresis (DGGE). They can also be discovered by direct sequencing of DNA samples pooled from different individuals or by comparing sequences from different DNA samples. With the rapid accumulation of sequence data in public and private databases, one can discover SNP by comparing sequences using computer programs (Z. Gu, L. Hillier and P. Y. Kwok, "Single nucleotide polymorphism hunting in cyberspace," Hum. Mutat. 1998; 12(4):221-225). SNP can be verified and genotype or haplotype of an individual can be determined by a variety of methods including direct sequencing and high throughput microarrays (P. Y. Kwok, "Methods for genotyping single nucleotide polymorphisms," Annu. Rev. Genomics Hum. Genet. 2001; 2:235-258; M. Kokoris, K. Dix, K. Moynihan, J. Mathis, B. Erwin, P. Grass, B. Hines and A. Duesterhoeft, "High-throughput SNP genotyping with the Masscode system," Mol. Diagn. 2000 Dec; 5(4):329-340). Using the methods described above, SNP were identified in the original transcript, 109P4D4 v.1, and its variants (see Figure 2J and Figure 2K). These alleles of the SNP, though shown separately here, can occur in different combinations (haplotypes) and in any one of the transcript variants (such as 109P4D4 v.4 or v.5) that contains the site of the SNP. Transcript variants v.4 and v.5 contained those SNP in the exons shared with variant v.3, and transcript variant v.9 contained all the SNP occurred in variant v.6 (see Figure 10). Example 7: Production of Recombinant 109PID4 in Prokaryotic Systems To express recombinant 109P1D4 and 109P1D4 variants in prokaryotic cells, the full or partial length 109P1D4 and 109P1D4 variant cDNA sequences are cloned into any one of a variety of expression vectors known in the art. One or more of the following regions of 109P1 D4 variants are expressed: the full length sequence presented in Figures 2 and 3, or any 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or more contiguous amino acids from 109P1 D4, variants, or analogs thereof. A. In vitro transcription and translation constructs: pCRIli: To generate 109P1 D4 sense and anti-sense RNA probes for RNA in situ investigations, pCRlI constructs (Invitrogen, Carlsbad CA) are generated encoding either all or fragments of the 109P1D4 cDNA. The pCRlI vector has Sp6 and T7 promoters flanking the insert to drive the transcription of 109PI D4 RNA for use as probes in RNA in situ hybridization experiments. These probes are used to analyze the cell and tissue expression of 109P1 D4 at the RNA level. Transcribed WO 2004/098515 PCT/US2004/013568 88 109P1D4 RNA representing the cDNA amino acid coding region of the 109P1D4 gene is used in in vitro translation systems such as the TnTTM Coupled Reticulolysate System (Promega, Corp., Madison, WI) to synthesize 109P1 D4 protein. B. Bacterial Constructs: oGEX Constructs: To generate recombinant 109P1D4 proteins in bacteria that are fused to the Glutathione S transferase (GST) protein, all or parts of the 109P1 D4 cDNA protein coding sequence are cloned into the pGEX family of GST-fusion vectors (Amersham Pharmacia Biotech, Piscataway, NJ). These constructs allow controlled expression of recombinant 109P1D4 protein sequences with GST fused at the amino-terminus and a six histidine epitope (6X His) at the carboxyl-terminus. The GST and 6X His tags permit purification of the recombinant fusion protein from induced bacteria with the appropriate affinity matrix and allow recognition of the fusion protein with anti-GST and anti-His antibodies. The 6X His tag is generated by adding 6 histidine codons to the cloning primer at the 3' end, e.g., of the open reading frame (ORF). A proteolytic cleavage site, such as the PreScissionTM recognition site in pGEX-6P-1, may be employed such that it permits cleavage of the GST tag from I 09P1 D4-related protein. The ampicillin resistance gene and pBR322 origin permits selection and maintenance of the pGEX plasmids in E. coi. pMAL Constructs: To generate, in bacteria, recombinant 109P1D4 proteins that are fused to maltose-binding protein (MBP), all or parts of the 109P1D4 cDNA protein coding sequence are fused to the MBP gene by cloning into the pMAL-c2X and pMAL-p2X vectors (New England Biolabs, Beverly, MA). These constructs allow controlled expression of recombinant I 09P1 D4 protein sequences with MBP fused at the amino-terminus and a 6X His epitope tag at the carboxyl terminus. The MBP and 6X His tags permit purification of the recombinant protein from induced bacteria with the appropriate affinity matrix and allow recognition of the fusion protein with anti-MBP and anti-His antibodies. The 6X His epitope tag is generated by adding 6 histidine codons to the 3 cloning primer. A Factor Xa recognition site permits cleavage of the pMAL tag from 109P1D4. The pMAL-c2X and pMAL-p2X vectors are optimized to express the recombinant protein in the cytoplasm or periplasm respectively. Periplasm expression enhances folding of proteins with disulfide bonds. In one embodiment, amino acids 24-419 of 109P1D4 variant I was cloned into the pMAL-c2X vector and was used to express the fusion protein. pET Constructs: To express 109P1D4 in bacterial cells, all or parts of the 109P1D4 cDNA protein coding sequence are cloned into the pET family of vectors (Novagen, Madison, WI). These vectors allow tightly controlled expression of recombinant 109P1 D4 protein in bacteria with and without fusion to proteins that enhance solubility, such as NusA and thioredoxin (Trx), and epitope tags, such as 6X His and S-Tag Tm that aid purification and detection of the recombinant protein. For example, constructs are made utilizing pET NusA fusion system 43.1 such that regions of the 109P1D4 protein are expressed as amino-terminal fusions to NusA. In 2 embodiments, amino acids 24-419 and 24-815 were cloned into pET43.1 vector and used to express the fusion protein. C. Yeast Constructs: PESC Constructs: To express 1 09P1 D4 in the yeast species Saccharomyces cerevisiae for generation of recombinant protein and functional studies, all or parts of the 109P1 D4 cDNA protein coding sequence are cloned into the pESC family of vectors each of which contain 1 of 4 selectable markers, HIS3, TRP1, LEU2, and URA3 (Stratagene, La Jolla, CA). These vectors allow controlled expression from the same plasmid of up to 2 different genes or cloned sequences containing either FlagTM or Myc epitope tags in the same yeast cell. This system is useful to confirm protein-protein interactions of 1 09P1 D4. In addition, expression in yeast yields similar post-translational modifications, such as glycosylations and phosphorylations, that are found when expressed in eukaryotic cells. pESP Constructs: To express 109P1 D4 in the yeast species Saccharomycespombe, all or parts of the 109P1D4 cONA protein coding sequence are cloned into the pESP family of vectors. These vectors allow controlled high level of WO 2004/098515 PCT/US2004/013568 89 expression of a 109P1 D4 protein sequence that is fused at either the amino terminus or at the carboxyl terminus to GST which aids purification of the recombinant protein. A FlagTMepitope tag allows detection of the recombinant protein with anti FlagTM antibody. Example 8: Production of Recombinant 109PiD4 in Higher Eukarvotic Systems A. Mammalian Constructs: To express recombinant 109P1D4 in eukaryotic cells, the full or partial length 109P1D4 cDNA sequences were cloned into any one of a variety of expression vectors known in the art. One or more of the following regions of 109P1 D4 were expressed in these constructs, amino acids I to 1021 or any 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18,19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or more contiguous amino acids from 109P1D4 v.1; amino acids I to 1054, 1 to 1347, 1 to 1337, 1 to 1310, 1 to 1037, 1 to 1048, 1 to 1340 of v.2, v.3, v.4, v.5, v.6, v.7, and v.8 respectively; or any 8, 9, 10, 11, 12,13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or more contiguous amino acids from 109P1D4 variants, or analogs thereof. The constructs can be transfected into any one of a wide variety of mammalian cells such as 293T cells. Transfected 293T cell lysates can be probed with the anti-109P1D4 polyclonal serum, described herein. pcDNA4/HisMax Constructs: To express 109P1D4 in mammalian cells, a 109P1D4 ORF, or portions thereof, of 109P1D4 are cloned into pcDNA4/HisMax Version A (Invitrogen, Carlsbad, CA). Protein expression is driven from the cytomegalovirus (CMV) promoter and the SPI6 translational enhancer. The recombinant protein has XpressTM and six histidine (6X His) epitopes fused to the amino-terminus. The pcDNA4/HisMax vector also contains the bovine growth hormone (BGH) polyadenylation signal and transcription termination sequence to enhance mRNA stability along with the SV40 origin for episomal replication and simple vector rescue in cell lines expressing the large T antigen. The Zeocin resistance gene allows for selection of mammalian cells expressing the protein and the ampicillin resistance gene and ColE1 origin permits selection and maintenance of the plasmid in E. coli. pcDNA3.1/MycHis Constructs: To express 109P1 D4 in mammalian cells, a 109P1 D4 ORF, or portions thereof, of 109P1D4 with a consensus Kozak translation initiation site was cloned into pcDNA3.1/MycHis Version A (Invitrogen, Carlsbad, CA). Protein expression is driven from the cytomegalovirus (CMV) promoter. The recombinant proteins have the myc epitope and 6X His epitope fused to the carboxyl-terminus. The pcDNA3.1/MycHis vector also contains the bovine growth hormone (BGH) polyadenylation signal and transcription termination sequence to enhance mRNA stability, along with the SV40 origin for episomal replication and simple vector rescue in cell lines expressing the large T antigen. The Neomycin resistance gene can be used, as it allows for selection of mammalian cells expressing the protein and the ampicillin resistance gene and ColEI origin permits selection and maintenance of the plasmid in E coli. The complete ORF of 109P1D4 v.1 was cloned into the pcDNA3.1/MycHis construct to generate 109P1D4.pcDNA3.1/MycHis. pcDNA3.1/CT-GFP-TOPO Construct: To express 109P1 D4 in mammalian cells and to allow detection of the recombinant proteins using fluorescence, a 109P1 D4 ORF, or portions thereof, with a consensus Kozak translation initiation site are cloned into pcDNA3.1/CT-GFP-TOPO (Invitrogen, CA). Protein expression is driven from the cytomegalovirus (CMV) promoter. The recombinant proteins have the Green Fluorescent Protein (GFP) fused to the carboxyl-terminus facilitating non-invasive, in vivo detection and cell biology studies. The pcDNA3.1 CT-GFP-TOPO vector also contains the bovine growth hormone (BGH) polyadenylation signal and transcription termination sequence to enhance mRNA stability along with the SV40 origin for episomal replication and simple vector rescue in cell lines expressing the large T antigen. The WO 2004/098515 PCT/US2004/013568 90 Neomycin resistance gene allows for selection of mammalian cells that express the protein, and the ampicillin resistance gene and ColE1 origin permits selection and maintenance of the plasmid in E. coli. Additional constructs with an amino terminal GFP fusion are made in pcDNA3.1/NT-GFP-TOPO spanning the entire length of a 109P1D4 protein. PAPtag: A 109P1D4 ORF, or portions thereof, is cloned into pAPtag-5 (GenHunter Corp. Nashville, TN). This construct generates an alkaline phosphatase fusion at the carboxyl-terminus of a 109P1D4 protein while fusing the IgGK signal sequence to the amino-terminus. Constructs are also generated in which alkaline phosphatase with an amino terminal IgGK signal sequence is fused to the amino-terminus of a 109P1 D4 protein. The resulting recombinant 1 09P1 D4 proteins are optimized for secretion into the media of transfected mammalian cells and can be used to identify proteins such as ligands or receptors that interact with 109P1 D4 proteins. Protein expression is driven from the CMV promoter and the recombinant proteins also contain myc and 6X His epitopes fused at the carboxyl-terminus that facilitates detection and purification. The Zeocin resistance gene present in the vector allows for selection of mammalian cells expressing the recombinant protein and the ampicillin resistance gene permits selection of the plasmid in E. coli. pTaa5: A 109P1D4 ORF, or portions thereof, were cloned into pTag-5. This vector is similar to pAPtag but without the alkaline phosphatase fusion. This construct generated 109P1D4 protein with an amino-terminal IgGK signal sequence and myc and 6X His epitope tags at the carboxyl-terminus that facilitate detection and affinity purification. The resulting recombinant I 09P1 D4 protein was optimized for secretion into the media of transfected mammalian cells, and was used as immunogen or ligand to identify proteins such as ligands or receptors that interact with the 109P1 D4 proteins. Protein expression is driven from the CMV promoter. The Zeocin resistance gene present in the vector allows for selection of mammalian cells expressing the protein, and the ampicillin resistance gene permits selection of the plasmid in E coil. PsecFc: A 109P1D4 ORF, or portions thereof, is also cloned into psecFc. The psecFc vector was assembled by cloning the human immunoglobulin GI (IgG) Fc (hinge, CH2, CH3 regions) into pSecTag2 (Invitrogen, California). This construct generates an igGI Fc fusion at the carboxyl-terminus of the 109P1 D4 proteins, while fusing the IgGK signal sequence to N-terminus. 109P1D4 fusions utilizing the murine IgGI Fo region are also used. The resulting recombinant 109P1D4 proteins are optimized for secretion into the media of transfected mammalian cells, and can be used as immunogens or to identify proteins such as ligands or receptors that interact with 1 D9PI D4 protein. Protein expression is driven from the CMV promoter. The hygromycin resistance gene present in the vector allows for selection of mammalian cells that express the recombinant protein, and the ampicillin resistance gene permits selection of the plasmid in E col. pSRc Constructs: To generate mammalian cell lines that express 109P1 D4 constitutively, 109P1 D4 ORF, or portions thereof, were cloned into pSRu constructs. Amphotropic and ecotropic retroviruses were generated by transfection of pSRax constructs into the 293T-I OA1 packaging line or co-transfection of pSRa and a helper plasmid (containing deleted packaging sequences) into the 293 cells, respectively. The retrovirus is used to infect a variety of mammalian cell lines, resulting in the integration of the cloned gene, 109P1D4, into the host cell-lines. Protein expression is driven from a long terminal repeat (LTR). The Neomycin resistance gene present in the vector allows for selection of mammalian cells that express the protein, and the ampicillin resistance gene and ColE1 origin permit selection and maintenance of the plasmid in E coli. The retroviral vectors can thereafter be used for infection and generation of various cell lines using, for example, PC3, NIH 3T3, TsuPrI, 293 or rat-I cells. Additional pSRa constructs are made that fuse an epitope tag such as the FLAGTM tag to the carboxyl-terminus of 109P1D4 sequences to allow detection using anti-Flag antibodies. For example, the FLAGTM sequence 5' GAT TAC AAG GAT GAC GAC GAT AAG 3' (SEQ ID NO: 56) is added to cloning primer at the 3 end of the ORF. Additional pSRux constructs are made to produce both amino-terminal and carboxyl-terminal GFP and myc/6X His fusion proteins of the full length 109P1D4 proteins.

WO 2004/098515 PCT/US2004/013568 91 Additional Viral Vectors: Additional constructs are made for viral-mediated delivery and expression of 109P1 D4. High virus titer leading to high level expression of 109P1D4 is achieved in viral delivery systems such as adenoviral vectors and herpes amplicon vectors. A 109P1 D4 coding sequence or fragments thereof are amplified by PCR and subcloned into the AdEasy shuttle vector (Stratagene). Recombination and virus packaging are performed according to the manufacturer's instructions to generate adenoviral vectors. Alternatively, 109P1D4 coding sequences or fragments thereof are cloned into the HSV-1 vector (imgenex) to generate herpes viral vectors. The viral vectors are thereafter used for infection of various cell lines such as PC3, NIH 3T3, 293 or rat-1 cells. Regulated Expression Systems: To control expression of 109P1D4 in mammalian cells, coding sequences of 109P1D4, or portions thereof, are cloned into regulated mammalian expression systems such as the T-Rex System (Invitrogen), the GeneSwitch System (Invitrogen) and the tightly-regulated Ecdysone System (Stratagene). These systems allow the study of the temporal and concentration dependent effects of recombinant 109P1D4. These vectors are thereafter used to control expression of 109P1D4 in various cell lines such as PC3, NIH 3T3, 293 or rat-1 cells. B. Baculovirus Expression Systems To generate recombinant 109P1D4 proteins in a baculovirus expression system, 109P1D4 ORF, or portions thereof, are cloned into the baculovirus transfer vector pBlueBac 4.5 (Invitrogen), which provides a His-tag at the N-terminus. Specifically, pBlueBac-1 09P1D4 is co-transfected with helper plasmid pBac-N-Blue (Invitrogen) into SF9 (Spodoptera frugiperda) insect cells to generate recombinant baculovirus (see Invitrogen Instruction manual for details). Baculovirus is then collected from cell supernatant and purified by plaque assay. Recombinant 109P1D4 protein is then generated by infection of HighFive insect cells (Invitrogen) with purified baculovirus. Recombinant 109P1D4 protein can be detected using anti-109P1D4 or anti-His-tag antibody. 109P1D4 protein can be purified and used in various cell-based assays or as immunogen to generate polyclonal and monoclonal antibodies specific for 109P1D4. Example 9: Antigenicity Profiles and Secondary Structure Figure(s) 5A-l, Figure 6A-1, Figure 7A-1, Figure 8A-l, and Figure 9A-I depict graphically five amino acid profiles of 109P1D4 variants 1 through 9, each assessment available by accessing the ProtScale website located on the World Wide Web at (.expasy.ch/cgi-bin/protscale.p) on the ExPasy molecular biology server. These profiles: Figure 5, Hydrophilicity, (Hopp T.P., Woods K.R., 1981. Proc. Nati. Acad. Sci. U.S.A. 78:3824 3828); Figure 6, Hydropathicity, (Kyte J., Doolittle R.F., 1982. J. Mol. Biol. 157:105-132); Figure 7, Percentage Accessible Residues (Janin J., 1979 Nature 277:491-492); Figure 8, Average Flexibility, (Bhaskaran R., and Ponnuswamy P.K., 1988. Int. J. Pept. Protein Res. 32:242-255); Figure 9, Beta-turn (Deleage, G., Roux B. 1987 Protein Engineering 1:289-294); and optionally others available in the art, such as on the ProtScale website, were used to identify antigenic regions of each of the 109P1D4 variant proteins. Each of the above amino acid profiles of 109P1D4 variants were generated using the following ProtScale parameters for analysis: 1) A window size of 9; 2) 100% weight of the window edges compared to the window center; and, 3) amino acid profile values normalized to lie between 0 and 1. Hydrophilicity (Figure 5), Hydropathicity (Figure 6) and Percentage Accessible Residues (Figure 7) profiles were used to determine stretches of hydrophilic amino acids (i.e., values greater than 0.5 on the Hydrophilicity and Percentage Accessible Residues profile, and values less than 0.5 on the Hydropathicity profile). Such regions are likely to be exposed to the aqueous environment, be present on the surface of the protein, and thus available for immune recognition, such as by antibodies. Average Flexibility (Figure 8) and Beta-turn (Figure 9) profiles determine stretches of amino acids (i.e., values WO 2004/098515 PCT/US2004/013568 92 greater than 0.5 on the Beta-turn profile and the Average Flexibility profile) that are not constrained in secondary structures such as beta sheets and alpha helices. Such regions are also more likely to be exposed on the protein and thus accessible to immune recognition, such as by antibodies. Antigenic sequences of the 109P1D4 variant proteins indicated, e.g., by the profiles set forth in Figure 5, Figure 6, Figure 7, Figure 8, and/or Figure 9 are used to prepare immunogens, either peptides or nucleic acids that encode them, to generate therapeutic and diagnostic anti-I 09P1 D4 antibodies. The immunogen can be any 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50 or more than 50 contiguous amino acids, or the corresponding nucleic acids that encode them, from the 109P1D4 protein variants listed in Figures 2 and 3. In particular, peptide immunogens of the invention can comprise, a peptide region of at least 5 amino acids of Figures 2 and 3 in any whole number increment that includes an amino acid position having a value greater than 0.5 in the Hydrophilicity profiles of Figure 5; a peptide region of at least 5 amino acids of Figures 2 and 3 in any whole number increment that includes an amino acid position having a value less than 0.5 in the Hydropathicity profile of Figure 6; a peptide region of at least 5 amino acids of Figures 2 and 3 in any whole number increment that includes an amino acid position having a value greater than 0.5 in the Percent Accessible Residues profiles of Figure 7; a peptide region of at least 5 amino acids of Figures 2 and 3 in any whole number increment that includes an amino acid position having a value greater than 0.5 in the Average Flexibility profiles on Figure 8 ; and, a peptide region of at least 5 amino acids of Figures 2 and 3 in any whole number increment that includes an amino acid position having a value greater than 0.5 in the Beta-turn profile of Figures 9. Peptide immunogens of the invention can also comprise nucleic acids that encode any of the forgoing. All immunogens of the invention, peptide or nucleic acid, can be embodied in human unit dose form, or comprised by a composition that includes a pharmaceutical excipient compatible with human physiology. The secondary structure of 109P1D4 protein variants, namely the predicted presence and location of alpha helices, extended strands, and random coils, are predicted from the primary amino acid sequence using the HNN - Hierarchical Neural Network method (NPS@: Network Protein Sequence Analysis TIBS 2000 March Vol. 25, No 3 [2911:147-150 Combet C., Blanchet C., Geourjon C. and Deleage G., http://pbil.ibcp.fr/cgi-bin/npsa.automatpl?page=npsa-nn.html), accessed from the ExPasy molecular biology server located on the World Wide Web at (www.expasy.ch/tools/). This analysis for protein variants I through 9 are shown in Figure 13A through 131 respectively. The percent of structure for each variant comprised of alpha helix, extended strand, and random doil is also indicated. Analysis for the potential presence of transmembrane domains in 109P1D4 variant proteins was carried out using a variety of transmembrane prediction algorithms accessed from the ExPasy molecular biology server located on the World Wide Web at (www.expasy.ch/tools/). Shown graphically in figures 13J-R are the results of analyses using the TMpred program (top panels) and the TMHMM program (bottom panels) of 109P1 D4 protein variants 1 through 9 respectively. Analyses of the variants using other structural prediction programs are summarized in Table VI and Table L. Example 10: Generation of 109P1D4 Polyconal Antibodies Polyclonal antibodies can be raised in a mammal, for example, by one or more injections of an immunizing agent and, if desired, an adjuvant. Typically, the immunizing agent and/or adjuvant will be injected in the mammal by multiple subcutaneous or intraperitoneal injections. In addition to immunizing with a full length 109P1D4 protein variant, computer algorithms are employed in design of immunogens that, based on amino acid sequence analysis contain characteristics of being antigenic and available for recognition by the immune system of the immunized host (see the Example entitled "Antigenicity Profiles and Secondary Structure"). Such regions would be predicted to be hydrophilic, flexible, in beta-turn conformations, and be exposed on the surface of the protein (see, e.g., Figure 5, Figure 6, Figure 7, Figure 8, or Figure 9 for WO 2004/098515 PCT/US2004/013568 93 amino acid profiles that indicate such regions of 109P1 D4 protein variant 1). For example, recombinant bacterial fusion proteins or peptides containing hydrophilic, flexible, beta-turn regions of 109P1 D4 protein variants are used as antigens to generate polyclonal antibodies in New Zealand White rabbits or monoclonal antibodies as described in the example entitled "Generation of 109PI D4 Monoclonal Antibodies (mAbs)". For example, in 109P1D4 variant 1, such regions include, but are not limited to, amino acids 22-39, amino acids 67-108, amino acids 200-232, amino acids 454-499, amino acids 525-537, amino acids 640-660, amino acids 834-880, and amino acids 929-942. It is useful to conjugate the immunizing agent to a protein known to be immunogenic in the mammal being immunized. Examples of such immunogenic proteins include, but are not limited to, keyhole limpet hemocyanin (KLH), serum albumin, bovine thyroglobulin, and soybean trypsin inhibitor. In 2 embodiments, peptides encoding amino acids 77-90 and amino acids 929-942 of 109P1D4 variant 1 were synthesized, conjugated to KLH, and used to immunize separate rabbits. Alternatively the immunizing agent may include all or portions of the 109P1 D4 variant proteins, analogs or fusion proteins thereof. For example, the 109P1 D4 variant 1 amino acid sequence can be fused using recombinant DNA techniques to any one of a variety of fusion protein partners that are well known in the art, such as glutathione-S-transferase (GST) and HIS tagged fusion proteins. In 1 embodiment, amino acids 24-419 of 109P1D4 variant 1 was fused to NUSa using recombinant techniques and the pET43.1 expression vector, expressed, purified and used to immunize a rabbit. Such fusion proteins are purified from induced bacteria using the appropriate affinity matrix. Other recombinant bacterial fusion proteins that may be employed include maltose binding protein, LacZ, thioredoxin, NusA, or an immunoglobulin constant region (see the section entitled "Production of 109P1 D4 in Prokaryotic Systems" and Current Protocols In Molecular Biology, Volume 2, Unit 16, Frederick M. Ausubul et al. eds., 1995; Linsley, P.S., Brady, W., Urnes, M., Grosmaire, L., Damle, N., and Ledbetter, J.(1991) J.Exp. Med. 174, 561-566). In addition to bacterial derived fusion proteins, mammalian expressed protein antigens are also used. These antigens are expressed from mammalian expression vectors such as the Tag5 and Fc-fusion vectors (see the section entitled "Production of Recombinant 109P1D4 in Eukaryotic Systems"), and retain post-translational modifications such as glycosylations found in native protein. In one embodiment, amino acids 24-812 of 109P1D4 variant 1 was cloned into the Tag5 mammalian secretion vector, and expressed in 293T cells (See Figure 20). The recombinant protein is purified by metal chelate chromatography from tissue culture supernatants of 293T cells stably expressing the recombinant vector. The purified Tag5 109P1D4 protein is then used as immunogen. During the immunization protocol, it is useful to mix or emulsify the antigen in adjuvants that enhance the immune response of the host animal. Examples of adjuvants include, but are not limited to, complete Freund's adjuvant (CFA) and MPL-TDM adjuvant (monophosphoryl Lipid A, synthetic trehalose dicorynomycolate). In a typical protocol, rabbits are initially immunized subcutaneously with up to 200 pig, typically 100-200 pag, of fusion protein or peptide conjugated to KLH mixed in complete Freund's adjuvant (CFA). Rabbits are then injected subcutaneously every two weeks with up to 200 Ig, typically 100-200 ig, of the immunogen in incomplete Freund's adjuvant (IFA). Test bleeds are taken approximately 7-10 days following each immunization and used to monitor the titer of the antiserum by ELISA. To test reactivity and specificity of immune serum, such as the rabbit serum derived from immunization with the NUSa-fusion of 109P1D4 variant I protein, the full-length 109P1D4 variant 1 cDNA is cloned into pCDNA 3.1 myc-his expression vector (Invitrogen, see the Example entitled "Production of Recombinant 109P1 D4 in Eukaryotic Systems"). After transfection of the constructs into 293T cells, cell lysates are probed with the anti-i 09P1 D4 serum to determine specific reactivity to denatured 109P1D4 protein using the Western blot technique. Probing with anti-His antibody serves as a positive control for expression of 109P1D4 in the transfected cells (See Figure 21). In addition, the immune serum is tested WO 2004/098515 PCT/US2004/013568 94 by fluorescence microscopy, flow cytometry and immunoprecipitation against 293T and other recombinant 109P1 D4 expressing cells to determine specific recognition of native protein. Western blot, immunoprecipitation, fluorescent microscopy, and flow cytometric techniques using cells that endogenously express 109P1D4 are also carried out to test reactivity and specificity. Anti-serum from rabbits immunized with 109P1D4 variant fusion proteins, such as GST and MBP fusion proteins, are purified by depletion of antibodies reactive to the fusion partner sequence by passage over an affinity column containing the fusion partner either alone or in the context of an irrelevant fusion protein. For example, antiserum derived from a NUSa 109P1D4 variant 1 fusion protein is first purified by passage over a column of MBP protein covalently coupled to AffiGel matrix (BioRad, Hercules, Calif.). The antiserum is then affinity purified by passage over a column composed of a NUSa 109P1D4 fusion protein covalently coupled to Affigel matrix. The serum is then further purified by protein G affinity chromatography to isolate the igG fraction. Sera from other His-tagged antigens and peptide immunized rabbits as well as fusion partner depleted sera are affinity purified by passage over a column matrix composed of the original protein immunogen or free peptide. Example 11: Generation of 109P1D4 Monoclonal Antibodies (mAbs) In one embodiment, therapeutic mAbs to 109P1D4 variants comprise those that react with epitopes specific for each variant protein or specific to sequences in common between the variants that would disrupt or modulate the biological function of the 109P1D4 variants, for example those that would disrupt the interaction with ligands and binding partners. Immunogens for generation of such mAbs include those designed to encode or contain the entire 109P1D4 protein variant sequence, regions predicted to contain functional motifs, and regions of the 109P1D4 protein variants predicted to be antigenic from computer analysis of the amino acid sequence (see, e.g., Figure 5, Figure 6, Figure 7, Figure 8, or Figure 9, and the Example entitled "Antigenicity Profiles and Secondary Structure"). Immunogens include peptides, recombinant bacterial proteins, and mammalian expressed Tag 5 proteins and human and murine IgG FO fusion proteins. In addition, cells engineered to express high levels of a respective 109P1D4 variant, such as 293T-109P1D4 variant I or 300.19 109P1D4 variant Imurine Pre-B cells, are used to immunize mice. To generate mAbs to a 109P1D4 variant, mice are first immunized intraperitoneally (IP) with, typically, 10-50 pig of protein immunogen or 107 109P1D4-expressing cells mixed in complete Freund's adjuvant. Mice are then subsequently immunized IP every 2-4 weeks with, typically, 10-50 pg of protein immunogen or 107 cells mixed in incomplete Freund's adjuvant. Alternatively, MPL-TDM adjuvant is used in immunizations. In addition to the above protein and cell-based immunization strategies, a DNA-based immunization protocol is employed in which a mammalian expression vector encoding a 109P1D4 variant sequence is used to immunize mice by direct injection of the plasmid DNA. For example, amino acids 24-812 of 109P1D4 of variant I is cloned into the Tag5 mammalian secretion vector and the recombinant vector will then be used as immunogen. In another example the same amino acids are cloned into an Fc-fusion secretion vector in which the 109P1D4 variant I sequence is fused at the amino-terminus to an IgK leader sequence and at the carboxyl terminus to the coding sequence of the human or murine igG Fc region. This recombinant vector is then used as immunogen. The plasmid immunization protocols are used in combination with purified proteins expressed from the same vector and with cells expressing the respective 109P1D4 variant. Alternatively, mice may be immunized directly into their footpads. In this case, 10-50 pg of protein immunogen or 107 254P1D6B-expressing cells are injected sub-cutaneously into the footpad of each hind leg. The first immunization is given with Titermax (SigmaTM) as an adjuvant and subsequent injections are given with Alum-gel in conjunction with CpG oligonucleotide sequences with the exception of the final injection which is given with PBS. Injections are given twice weekly WO 2004/098515 PCT/US2004/013568 95 (every three to four days) for a period of 4 weeks and mice are sacrificed 3-4 days after the final injection, at which point lymph nodes immediately draining from the footpad are harvested and the B-cells are collected for use as antibody producing fusion partners. During the immunization protocol, test bleeds are taken 7-10 days following an injection to monitor titer and specificity of the immune response. Once appropriate reactivity and specificity is obtained as determined by ELISA, Western blotting, immunoprecipitation, fluorescence microscopy, and flow cytometric analyses, fusion and hybridoma generation is then carried out with established procedures well known in the art (see, e.g., Harlow and Lane, 1988). In one embodiment for generating 109P1 D4 monoclonal antibodies, a Tag5 antigen of variant 1 encoding amino acids 14-812 is expressed in 293T cells and purified from conditioned media. Balb C mice are initially immunized intraperitoneally with 25 ptg of the Tag5 109P1D4 variant 1 protein mixed in complete Freund's adjuvant. Mice are subsequently immunized every two weeks with 25 pg of the antigen mixed in incomplete Freund's adjuvant for a total of three immunizations. ELISA using the Tag5 antigen determines the titer of serum from immunized mice. Reactivity and specificity of serum to full length 109P1 D4 variant 1 protein is monitored by Western blotting, immunoprecipitation and flow cytometry using 293T cells transfected with an expression vector encoding the 109P1D4 variant I cDNA (see e.g., the Example entitled "Production of Recombinant 109P1D4 in Higher Eukaryotic Systems" and Figure 21). Other recombinant 109P1 D4 variant 1-expressing cells or cells endogenously expressing 109P1 D4 variant 1 are also used. Mice showing the strongest reactivity are rested and given a final injection of antigen in PBS and then sacrificed four days later. The spleens of the sacrificed mice are harvested and fused to SPO/2 myeloma cells using standard procedures (Harlow and Lane, 1988). Supernatants from HAT selected growth wells are screened by ELISA, Western blot, immunoprecipitation, fluorescent microscopy, and flow cytometry to identify 109P1 D4 specific antibody-producing clones. To generate monoclonal antibodies that are specific for a 109P1D4 variant protein, immunogens are designed to encode sequences unique for each variant. In one embodiment, an antigenic peptide composed of amino acids 1-29 of 1 09P1D4 variant 2 is coupled to KLH to derive monoclonal antibodies specific to 109P1 D4 variant 2. In another embodiment, an antigenic peptide comprised of amino acids 1-23 of 109P1 D4 variant 6 is coupled to KLH and used as immunogen to derive varaiant 6 specific MAbs. In another example, a GST-fusion protein encoding amino acids 1001 -1347 of variant 3 is used as immunogen to generate antibodies that would recognize variants 3, 4, 5, and 8, and distinguish them from variants 1, 2, 6, 7and 9. Hybridoma supernatants are then screened on the respective antigen and then further screened on cells expressing the specific variant and cross-screened on cells expressing the other variants to derive variant specific monoclonal antibodies. The binding affinity of 109P1 D4 variant specific monoclonal antibodies are determined using standard technologies. Affinity measurements quantify the strength of antibody to epitope binding and are used to help define which 1 09P1 D4 variant monoclonal antibodies preferred for diagnostic or therapeutic use, as appreciated by one of skill in the art. The BlAcore system (Uppsala, Sweden) is a preferred method for determining binding affinity. The BlAcore system uses surface plasmon resonance (SPR, Welford K. 1991, Opt. Quant. Elect. 23:1; Morton and Myszka, 1998, Methods in Enzymology 295: 268) to monitor biomolecular interactions in real time. BlAcore analysis conveniently generates association rate constants, dissociation rate constants, equilibrium dissociation constants, and affinity constants. Alternatively, equilibrium binding analysis of MAbs on 109P1D4-expressing cells can be used to determine affinity. Example 12: HLA Class I and Class I Binding Assays HLA class I and class 11 binding assays using purified HLA molecules are performed in accordance with disclosed protocols (e.g., PCT publications WO 94120127 and WO 94/03205; Sidney et al., Current Protocols in Immunology 18.3.1 WO 2004/098515 PCT/US2004/013568 96 (1998); Sidney, et al., J. Immunol. 154:247 (1995); Sette, et aL, Mol. Immunol. 31:813 (1994)). Briefly, purified MHC molecules (5 to 500 nM) are incubated with various unlabeled peptide inhibitors and 1-10 nM 12 1-radiolabeled probe peptides as described. Following incubation, MHC-peptide complexes are separated from free peptide by gel filtration and the fraction of peptide bound is determined. Typically, in preliminary experiments, each MHC preparation is titered in the presence of fixed amounts of radioiabeled peptides to determine the concentration of HLA molecules necessary to bind 10 20% of the total radioactivity. All subsequent inhibition and direct binding assays are performed using these HLA concentrations. Since under these conditions [label]<[HLA] and IC5o0:[HLA], the measured IC5o values are reasonable approximations of the true KD values. Peptide inhibitors are typically tested at concentrations ranging from 120 [Ig/ml to 1.2 nglml, and are tested in two to four completely independent experiments. To allow comparison of the data obtained in different experiments, a relative binding figure is calculated for each peptide by dividing the IC5o of a positive control for inhibition by the iCso for each tested peptide (typically unlabeled versions of the radiolabeled probe peptide). For database purposes, and inter-experiment comparisons, relative binding values are compiled. These values can subsequently be converted back into ICso nM values by dividing the ICoo nM of the positive controls for inhibition by the relative binding of the peptide of interest. This method of data compilation is accurate and consistent for comparing peptides that have been tested on different days, or with different lots of purified MHC. Binding assays as outlined above may be used to analyze HLA supermotif and/or HLA motif-bearing peptides (see Table IV). Example 13: Identification of HLA Supermotif- and Motif-Bearing CTL Candidate Epitopes HLA vaccine compositions of the invention can include multiple epitopes. The multiple epitopes can comprise multiple HLA supermotifs or motifs to achieve broad population coverage. This example illustrates the identification and confirmation of supermotif- and motif-bearing epitopes for the inclusion in such a vaccine composition. Calculation of population coverage is performed using the strategy described below. Computer searches and algorithms for identification of supermotif and/or motif-bearing epitopes The searches performed to identify the motif-bearing peptide sequences in the Example entitled "Antigenicity Profiles" and Tables VIII-XXI and XXIl-XLIX employ the protein sequence data from the gene product of 109P1 D4 set forth in Figures 2 and 3, the specific search peptides used to generate the tables are listed in Table VII. Computer searches for epitopes bearing HLA Class I or Class i1 supermotifs or motifs are performed as follows. All translated 109P1D4 protein sequences are analyzed using a text string search software program to identify potential peptide sequences containing appropriate HLA binding motifs; such programs are readily produced in accordance with information in the art in view of known motif/supermotif disclosures. Furthermore, such calculations can be made mentally. Identified A2-, A3-, and DR-supermotif sequences are scored using polynomial algorithms to predict their capacity to bind to specific HLA-Class I or Class 1I molecules. These polynomial algorithms account for the impact of different amino acids at different positions, and are essentially based on the premise that the overall affinity (or AG) of peptide-HLA molecule interactions can be approximated as a linear polynomial function of the type: "AG"= a1; x a21 x a31...... x an! where ati is a coefficient which represents the effect of the presence of a given amino acid () at a given position (f) along the sequence of a peptide of n amino acids. The crucial assumption of this method is that the effects at each position are essentially independent of each other (i.e., independent binding of individual side-chains). When residue j occurs at position i in the peptide, it is assumed to contribute a constant amount j to the free energy of binding of the peptide WO 2004/098515 PCT/US2004/013568 97 irrespective of the sequence of the rest of the peptide. The method of derivation of specific algorithm coefficients has been described in Gulukota et al., J. Mol. Biol. 267:1258-126, 1997; (see also Sidney et aL., Human Immunol. 45:79-93, 1996; and Southwood et al., J. Immunol. 160:3363 3373, 1998). Briefly, for all i positions, anchor and non-anchor alike, the geometric mean of the average relative binding (ARB) of all peptides carrying j is calculated relative to the remainder of the group, and used as the estimate of ji. For Class 11 peptides, if multiple alignments are possible, only the highest scoring alignment is utilized, following an iterative procedure. To calculate an algorithm score of a given peptide in a test set, the ARB values corresponding to the sequence of the peptide are multiplied. If this product exceeds a chosen threshold, the peptide is predicted to bind. Appropriate thresholds are chosen as a function of the degree of stringency of prediction desired. Selection of HLA-A2 supertype cross-reactive peptides Protein sequences from 109P1D4 are scanned utilizing motif identification software, to identify 8-, 9- 10- and 11 mer sequences containing the HLA-A2-supermotif main anchor specificity. Typically, these sequences are then scored using the protocol described above and the peptides corresponding to the positive-scoring sequences are synthesized and tested for their capacity to bind purified HLA-A*0201 molecules in vitro (HLA-A*0201 is considered a prototype A2 supertype molecule). These peptides are then tested for the capacity to bind to additional A2-supertype molecules (A*0202, A*0203, A*0206, and A*6802). Peptides that bind to at least three of the five A2-supertype alleles tested are typically deemed A2 supertype cross-reactive binders. Preferred peptides bind at an affinity equal to or less than 500 nM to three or more HLA A2 supertype molecules. Selection of HLA-A3 supermotif-bearing epitopes The 109P1 D4 protein sequence(s) scanned above is also examined for the presence of peptides with the HLA-A3 supermotif primary anchors. Peptides corresponding to the HLA A3 supermotif-bearing sequences are then synthesized and tested for binding to HLA-A*0301 and HLA-A*1101 molecules, the molecules encoded by the two most prevalent A3 supertype alleles. The peptides that bind at least one of the two alleles with binding affinities of <500 nM, often < 200 nM, are then tested for binding cross-reactivity to the other common A3-supertype alleles (e.g., A*3101, A*3301, and A*6801) to identify those that can bind at least three of the five HLA-A3-supertype molecules tested. Selection of HLA-B7 supermotif bearing epitopes The 109P1 D4 protein(s) scanned above is also analyzed for the presence of 8-, 9- 10-, or 1 1-mer peptides with the HLA-B7-supermotif. Corresponding peptides are synthesized and tested for binding to HLA-B*0702, the molecule encoded by the most common B7-supertype allele (i.e., the prototype B7 supertype allele). Peptides binding B*0702 with IC50 of 500 nM are identified using standard methods. These peptides are then tested for binding to other common B7-supertype molecules (e.g., B*3501, B*5101, B*5301, and B*5401). Peptides capable of binding to three or more of the five B7 supertype alleles tested are thereby identified. Selection of Al and A24 motif-bearinq epitopes To further increase population coverage, HLA-A1 and -A24 epitopes can also be incorporated into vaccine compositions. An analysis of the 109P1D4 protein can also be performed to identify HLA-A1- and A24-motif-containing sequences.

WO 2004/098515 PCT/US2004/013568 98 High affinity and/or cross-reactive binding epitopes that bear other motif and/or supermotifs are identified using analogous methodology. Example 14: Confirmation of Immunogenicity Cross-reactive candidate CTL A2-supermotif-bearing peptides that are identified as described herein are selected to confirm in vitro immunogenicity. Confirmation is performed using the following methodology: Target Cell Lines for Cellular Screenino: The .221A2.1 cell line, produced by transferring the HLA-A2.1 gene into the HLA-A, -B, -C null mutant human B lymphoblastoid cell line 721.221, is used as the peptide-loaded target to measure activity of HLA-A2. I-restricted CTL. This cell line is grown in RPMI-1640 medium supplemented with antibiotics, sodium pyruvate, nonessential amino acids and 10% (v/v) heat inactivated FCS. Cells that express an antigen of interest, or transfectants comprising the gene encoding the antigen of interest, can be used as target cells to confirm the ability of peptide-specific CTLs to recognize endogenous antigen. Primary CTL Induction Cultures: Generation of Dendritic Cells (DC): PBMCs are thawed in RPMI with 30 ptg/ml DNAse, washed twice and resuspended in complete medium (RPMI-1640 plus 5% AB human serum, non-essential amino acids, sodium pyruvate, L glutamine and penicillinistreptomycin). The monocytes are purified by plating 10 x 106 PBMC/well in a 6-well plate. After 2 hours at 37*C, the non-adherent cells are removed by gently shaking the plates and aspirating the supernatants. The wells are washed a total of three times with 3 ml RPMI to remove most of the non-adherent and loosely adherent cells. Three ml of complete medium containing 50 ng/ml of GM-CSF and 1,000 U/mi of IL-4 are then added to each well. TNFc is added to the DCs on day 6 at 75 ng/ml and the cells are used for CTL induction cultures on day 7. Induction of CTL with DC and Peptide: CD8+ T-cells are isolated by positive selection with Dynal immunomagnetic beads (Dynabeads@ M-450) and the detacha-bead@ reagent. Typically about 200-250x106 PBMC are processed to obtain 24x10 6 CD8+ T-cells (enough for a 48-well plate culture). Briefly, the PBMCs are thawed in RPMI with 30pg/ml DNAse, washed once with PBS containing 1% human AB serum and resuspended in PBS/1% AB serum at a concentration of 20x1O 6 cells/ml. The magnetic beads are washed 3 times with PBS/AB serum, added to the cells (140pl beads/20x106 cells) and incubated for 1 hour at 4 0 C with continuous mixing. The beads and cells are washed 4x with PBS/AB serum to remove the nonadherent cells and resuspended at 100x10 6 cells/mI (based on the original cell number) in PBS/AB serum containing 100pi/mi detacha-bead@ reagent and 30 pg/ml DNAse. The mixture is incubated for 1 hour at room temperature with continuous mixing. The beads are washed again with PBS!AB/DNAse to collect the CD8+ T-cells. The DC are collected and centrifuged at 1300 rpm for 5-7 minutes, washed once with PBS with 1% BSA, counted and pulsed with 40pg/ml of peptide at a cell concentration of 1-2x10 6 /ml in the presence of 3pg/ml &12- microglobulin for 4 hours at 201C. The DC are then irradiated (4,200 rads), washed 1 time with medium and counted again. Setting up induction cultures: 0.25 ml cytokine-generated DC (at 1x10 5 cells/ml) are co-cultured with 0.25ml of CD8+ T-cells (at 2x10 6 cell/ml) in each well of a 48-well plate in the presence of 10 ng/ml of IL-7. Recombinant human IL-10 is added the next day at a final concentration of 10 ng/ml and rhuman IL-2 is added 48 hours later at 10 IU/ml. Restimulation of the induction cultures with peptide-pulsed adherent cells: Seven and fourteen days after the primary induction, the cells are restimulated with peptide-pulsed adherent cells. The PBMCs are thawed and washed twice with RPMI and DNAse. The cells are resuspended at 5x10 6 cells/mi and irradiated at -4200 rads. The PBMCs are plated at 2x10 6 in 0.5 ml complete medium per well and incubated for 2 hours at 37"C. The plates are washed twice with RPMi by tapping the plate gently to remove the nonadherent cells and the adherent cells pulsed with lOpg/ml of peptide in the WO 2004/098515 PCT/US2004/013568 99 presence of 3 pg/ml 52 microglobulin in 0.25ml RPMI/5%AB per well for 2 hours at 370C. Peptide solution from each well is aspirated and the wells are washed once with RPMI. Most of the media is aspirated from the induction cultures (CD8+ cells) and brought to 0.5 ml with fresh media. The cells are then transferred to the wells containing the peptide-pulsed adherent cells. Twenty four hours later recombinant human IL-10 is added at a final concentration of 10 ng/ml and recombinant human IL2 is added the next day and again 2-3 days later at 501UIml (Tsai et al., Critical Reviews in Immunology 18(1-2):65-75, 1998). Seven days later, the cultures are assayed for CTL activity in a 5 1 Cr release assay. In some experiments the cultures are assayed for peptide-specific recognition in the in situ IFNy ELISA at the time of the second restimulation followed by assay of endogenous recognition 7 days later. After expansion, activity is measured in both assays for a side-by-side comparison. Measurement of CTL lytic activity by 5 1 Cr release. Seven days after the second restimulation, cytotoxicity is determined in a standard (5 hr) 5 1 Cr release assay by assaying individual wells at a single E:T. Peptide-pulsed targets are prepared by incubating the cells with 10pg/ml peptide overnight at 370C. Adherent target cells are removed from culture flasks with trypsin-EDTA. Target cells are labeled with 200pCi of 3 1 Cr sodium chromate (Dupont, Wilmington, DE) for 1 hour at 370C. Labeled target cells are resuspended at 106 per ml and diluted 1:10 with K562 cells at a concentration of 3.3x10 6 /ml (an NK-sensitive erythroblastoma cell line used to reduce non specific lysis). Target cells (100 pl) and effectors (100pl) are plated in 96 well round-bottom plates and incubated for 5 hours at 370C. At that time, 100 pl of supernatant are collected from each well and percent lysis is determined according to the formula: [(cpm of the test sample- cpm of the spontaneous 5 1Cr release sample)/(cpm of the maximal 5 1 Cr release sample cpm of the spontaneous 5 1 Cr release sample)] x 100. Maximum and spontaneous release are determined by incubating the labeled targets with 1% Triton X-100 and media alone, respectively. A positive culture is defined as one in which the specific lysis (sample- background) is 10% or higher in the case of individual wells and is 15% or more at the two highest E:T ratios when expanded cultures are assayed. In situ Measurement of Human IFNy Production as an Indicator of Peptide-specific and Endogenous Recognition Immulon 2 plates are coated with mouse anti-human IFN 7 monoclonal antibody (4 pg/ml 0.1M NaHCO3, pH8.2) overnight at 4*C. The plates are washed with Ca 2 +, Mg 2 +-free PBS/0.05% Tween 20 and blocked with PBS/10% FCS for two hours, after which the CTLs (100 piwell) and targets (100 pl/well) are added to each well, leaving empty wells for the standards and blanks (which received media only). The target cells, either peptide-pulsed or endogenous targets, are used at a concentration of 1x106 cells/ml. The plates are incubated for 48 hours at 37*C with 5% C02. Recombinant human IFN-gamma is added to the standard wells starting at 400 pg or 1200pg/100 microliter/well and the plate incubated for two hours at 37*C. The plates are washed and 100 pl of biotinylated mouse anti-human IFN gamma monoclonal antibody (2 microgram/ml in PBS/3%FCS/0.05% Tween 20) are added and incubated for 2 hours at room temperature. After washing again, 100 microliter HRP-streptavidin (1:4000) are added and the plates incubated for one hour at room temperature. The plates are then washed 6x with wash buffer, 100 microliter/well developing solution (TMB 1:1) are added, and the plates allowed to develop for 5-15 minutes. The reaction is stopped with 50 microliter/well 1M H3P04 and read at OD450. A culture is considered positive if it measured at least 50 pg of IFN-gamma/well above background and is twice the background level of expression. CTL Expansion. Those cultures that demonstrate specific lytic activity against peptide-pulsed targets and/or tumor targets are expanded over a two week period with anti-CD3. Briefly, 5x10 4 CD8+ cells are added to a T25 flask containing the following: WO 2004/098515 PCT/US2004/013568 100 xI 06 irradiated (4,200 rad) PBMC (autologous or allogeneic) per ml, 2x10 5 irradiated (8,000 rad) EBV- transformed cells per ml, and OKT3 (anti-CD3) at 30ng per ml in RPMI-1 640 containing 10% (vlv) human AB serum, non-essential amino acids, sodium pyruvate, 25pM 2-mercaptoethanol, L-glutamine and penicillin/streptomycin. Recombinant human IL2 is added 24 hours later at a final concentration of 200lU/ml and every three days thereafter with fresh media at 50lUlmi. The cells are split if the cell concentration exceeds 1x1O6/ml and the cultures are assayed between days 13 and 15 at E:T ratios of 30, 10, 3 and 1:1 in the 5 1Cr release assay or at x10 6 /ml in the in situ IFNy assay using the same targets as before the expansion. Cultures are expanded in the absence of anti-CD3+ as follows. Those cultures that demonstrate specific lytic activity against peptide and endogenous targets are selected and 5x10 4 CD8+ cells are added to a T25 flask containing the following: 1x106 autologous PBMC per ml which have been peptide-pulsed with 10 pg/ml peptide for two hours at 37*C and irradiated (4,200 rad); 2x105 irradiated (8,000 rad) EBV-transformed cells per ml RPMi-1640 containing 10%(v/v) human AB serum, non-essential AA, sodium pyruvale, 25mM 2-ME, L-glutamine and gentamicin. Immunogenicity of A2 supermotif-bearing peptides A2-supermotif cross-reactive binding peptides are tested in the cellular assay for the ability to induce peptide specific CTL in normal individuals. In this analysis, a peptide is typically considered to be an epitope if it induces peptide specific CTLs in at least individuals, and preferably, also recognizes the endogenously expressed peptide. Immunogenicity can also be confirmed using PBMCs isolated from patients bearing a tumor that expresses 109P1D4. Briefly, PBMCs are isolated from patients, re-stimulated with peptide-pulsed monocytes and assayed for the ability to recognize peptide-pulsed target cells as well as transfected cells endogenously expressing the antigen. Evaluation of A*03A1 1 immunogenicity HLA-A3 supermotif-bearing cross-reactive binding peptides are also evaluated for immunogenicity using methodology analogous for that used to evaluate the immunogenicity of the HLA-A2 supermotif peptides. Evaluation of B7 immunogenicity Immunogenicity screening of the B7-supertype cross-reactive binding peptides identified as set forth herein are confirmed in a manner analogous to the confirmation of A2-and A3-supermotif-bearing peptides. Peptides bearing other supermotifs/motifs, e.g., HLA-A1, HLA-A24 etc. are also confirmed using similar methodology Example 15: Implementation of the Extended Supermotif to Improve the Binding Capacity of Native Epitopes by Creating Analogs HLA motifs and supermotifs (comprising primary andfor secondary residues) are useful in the identification and preparation of highly cross-reactive native peptides, as demonstrated herein. Moreover, the definition of HLA motifs and supermotifs also allows one to engineer highly cross-reactive epitopes by identifying residues within a native peptide sequence which can be analoged to confer upon the peptide certain characteristics, e.g. greater cross-reactivity within the group of HLA molecules that comprise a supertype, andlor greater binding affinity for some or all of those HLA molecules. Examples of analoging peptides to exhibit modulated binding affinity are set forth in this example. Analoging at Primary Anchor Residues Peptide engineering strategies are implemented to further increase the cross-reactivity of the epitopes. For example, the main anchors of A2-supermotif-bearing peptides are altered, for example, to introduce a preferred L, I, V, or M at position 2, and I or V at the C-terminus. To analyze the cross-reactivity of the analog peptides, each engineered analog is initially tested for binding to the prototype A2 supertype allele A*0201, then, if A*0201 binding capacity is maintained, for A2-supertype cross-reactivity.

WO 2004/098515 PCT/US2004/013568 101 Alternatively, a peptide is confirmed as binding one or all supertype members and then analoged to modulate binding affinity to any one (or more) of the supertype members to add population coverage. The selection of analogs for immunogenicity in a cellular screening analysis is typically further restricted by the capacity of the parent wild type (WT) peptide to bind at least weakly, i.e., bind at an ICso of 5000nM or less, to three of more A2 supertype alleges. The rationale for this requirement is that the WT peptides must be present endogenously in sufficient quantity to be biologically relevant. Analoged peptides have been shown to have increased immunogenicity and cross reactivity by T cells specific for the parent epitope (see, e.g., Parkhurst et al., J. Immunol. 157:2539, 1996; and Pogue et al., Proc. Natl. Acad. Sci. USA 92:8166, 1995). In the cellular screening of these peptide analogs, it is important to confirm that analog-specific CTLs are also able to recognize the wild-type peptide and, when possible, target cells that endogenously express the epitope. Analoging of HLA-A3 and B7-supermotif-bearing peptides Analogs of HLA-A3 supermotif-bearing epitopes are generated using strategies similar to those employed in analoging HLA-A2 supermotif-bearing peptides. For example, peptides binding to 3/5 of the A3-supertype molecules are engineered at primary anchor residues to possess a preferred residue (V, S, M, or A) at position 2. The analog peptides are then tested for the ability to bind A*03 and A*1 1 (prototype A3 supertype alleles). Those peptides that demonstrate 500 nM binding capacity are then confirmed as having A3-supertype cross-reactivity. Similarly to the A2- and A3- motif bearing peptides, peptides binding 3 or more B7-supertype alleles can be improved, where possible, to achieve increased cross-reactive binding or greater binding affinity or binding half life. B7 supermotif-bearing peptides are, for example, engineered to possess a preferred residue (V, I, L, or F) at the C-terminal primary anchor position, as demonstrated by Sidney et al. (J. Immunol. 157:3480-3490, 1996). Analoging at primary anchor residues of other motif and/or supermotif-bearing epitopes is performed in a like manner. The analog peptides are then be confirmed for immunogenicity, typically in a cellular screening assay. Again, it is generally important to demonstrate that analog-specific CTLs are also able to recognize the wild-type peptide and, when possible, targets that endogenously express the epitope. Analoging at Secondary Anchor Residues Moreover, HLA supermotifs are of value in engineering highly cross-reactive peptides and/or peptides that bind HLA molecules with increased affinity by identifying particular residues at secondary anchor positions that are associated with such properties. For example, the binding capacity of a B7 supermotif-bearing peptide with an F residue at position 1 Is analyzed. The peptide is then analoged to, for example, substitute L for F at position 1. The analoged peptide is evaluated for increased binding affinity, binding half life and/or increased cross-reactivity. Such a procedure identifies analoged peptides with enhanced properties. Engineered analogs with sufficiently improved binding capacity or cross-reactivity can also be tested for immunogenicity in HLA-B7-transgenic mice, following for example, IFA immunization or lipopeptide immunization. Analoged peptides are additionally tested for the ability to stimulate a recall response using PBMC from patients with 109P1 D4 expressing tumors. Other analoaing strategies Another form of peptide analoging, unrelated to anchor positions, involves the substitution of a cysteine with a amino butyric acid. Due to its chemical nature, cysteine has the propensity to form disulfide bridges and sufficiently alter the WO 2004/098515 PCT/US2004/013568 102 peptide structurally so as to reduce binding capacity. Substitution of a-amino butyric acid for cysteine not only alleviates this problem, but has been shown to improve binding and crossbinding capabilities in some instances (see, e.g., the review by Sette et al., In: Persistent Viral Infections, Eds. R. Ahmed and i. Chen, John Wiley & Sons, England, 1999). Thus, by the use of single amino acid substitutions, the binding properties and/or cross-reactivity of peptide ligands for HLA supertype molecules can be modulated. Example 16: Identification and confirmation of 109P1D4-derived sequences with HLA-DR binding motifs Peptide epitopes bearing an HLA class Il supermotif or motif are identified and confirmed as outlined below using methodology similar to that described for HLA Class I peptides. Selection of HLA-DR-supermotif-bearina epitopes. To identify 109P1 D4-derived, HLA class 11 HTL epitopes, a 109P1 D4 antigen is analyzed for the presence of sequences bearing an HLA-DR-motif or supermotif. Specifically, 15-mer sequences are selected comprising a DR supermotif, comprising a 9-mer core, and three-residue N- and C-terminal flanking regions (15 amino acids total). Protocols for predicting peptide binding to DR molecules have been developed (Southwood et al., J. Immunol. 160:3363-3373, 1998). These protocols, specific for individual DR molecules, allow the scoring, and ranking, of 9-mer core regions. Each protocol not only scores peptide sequences for the presence of DR-supermotif primary anchors (i.e., at position 1 and position 6) within a 9-mer core, but additionally evaluates sequences for the presence of secondary anchors. Using allele-specific selection tables (see, e.g., Southwood et al, ibid.), it has been found that these protocols efficiently select peptide sequences with a high probability of binding a particular DR molecule. Additionally, it has been found that performing these protocols in tandem, specifically those for DRI, DR4w4, and DR7, can efficiently select DR cross-reactive peptides. The 109P1D4-derived peptides identified above are tested for their binding capacity for various common HLA-DR molecules. All peptides are initially tested for binding to the DR molecules in the primary panel: DR1, DR4w4, and DR7. Peptides binding at least two of these three DR molecules are then tested for binding to DR2w2 P1, DR2w2 P2, DR6w1 9, and DR9 molecules in secondary assays. Finally, peptides binding at least two of the four secondary panel DR molecules, and thus cumulatively at least four of seven different DR molecules, are screened for binding to DR4w1 5, DR5w1 1, and DR8w2 molecules in tertiary assays. Peptides binding at least seven of the ten DR molecules comprising the primary, secondary, and tertiary screening assays are considered cross-reactive DR binders. 109P1 D4-derived peptides found to bind common HLA-DR alleles are of particular interest. Selection of DR3 motif peptides Because HLA-DR3 is an allele that is prevalent in Caucasian, Black, and Hispanic populations, DR3 binding capacity is a relevant criterion in the selection of HTL epitopes. Thus, peptides shown to be candidates may also be assayed for their DR3 binding capacity. However, in view of the binding specificity of the DR3 motif, peptides binding only to DR3 can also be considered as candidates for inclusion in a vaccine formulation. To efficiently identify peptides that bind DR3, target 109P1 D4 antigens are analyzed for sequences carrying one of the two DR3-specific binding motifs reported by Geluk et a. (J. Immunol. 152:5742-5748, 1994). The corresponding peptides are then synthesized and confirmed as having the ability to bind DR3 with an affinity of I pM or better, i.e., less than 1 pM. Peptides are found that meet this binding criterion and qualify as HLA class 11 high affinity binders. DR3 binding epitopes identified in this manner are included in vaccine compositions with DR supermotif-bearing peptide epitopes. Similarly to the case of HLA class I motif-bearing peptides, the class Il motif-bearing peptides are analoged to WO 2004/098515 PCT/US2004/013568 103 improve affinity or cross-reactivity. For example, aspartic acid at position 4 of the 9-mer core sequence is an optimal residue for DR3 binding, and substitution for that residue often improves DR 3 binding. Example 17: Immunogenicity of 109P1D4-derived HTL epitopes This example determines immunogenic DR supermotif- and DR3 motif-bearing epitopes among those identified using the methodology set forth herein. Immunogenicity of HTL epitopes are confirmed in a manner analogous to the determination of immunogenicity of CTL epitopes, by assessing the ability to stimulate HTL responses and/or by using appropriate transgenic mouse models. Immunogenicity is determined by screening for: 1.) in vitro primary induction using normal PBMC or 2.) recall responses from patients who have 109P1D4-expressing tumors. Example 18: Calculation of phenotypic frequencies of HLA-supertypes in various ethnic backgrounds to determine breadth of population coverage This example illustrates the assessment of the breadth of population coverage of a vaccine composition comprised of multiple epitopes comprising multiple supermotifs and/or motifs. In order to analyze population coverage, gene frequencies of HLA alleles are determined. Gene frequencies for each HLA allele are calculated from antigen or allele frequencies utilizing the binomial distribution formulae gf=1-(SQRT(1 af)) (see, e.g., Sidney et al., Human Immunol. 45:79-93, 1996). To obtain overall phenotypic frequencies, cumulative gene frequencies are calculated, and the cumulative antigen frequencies derived by the use of the inverse formula [af=1-(l-Cgf) 2 1. Where frequency data is not available at the level of DNA typing, correspondence to the serologically defined antigen frequencies is assumed. To obtain total potential supertype population coverage no linkage disequilibrium is assumed, and only alleles confirmed to belong to each of the supertypes are included (minimal estimates). Estimates of total potential coverage achieved by inter-loci combinations are made by adding to the A coverage the proportion of the non-A covered population that could be expected to be covered by the B alleles considered (e.g., total=A+B*(1-A)). Confirmed members of the A3-like supertype are A3, Al1, A31, A*3301, and A*6801. Although the A3-like supertype may also include A34, A66, and A*7401, these alleles were not included in overall frequency calculations. Likewise, confirmed members of the A2-like supertype family are A*0201, A*0202, A*0203, A*0204, A*0205, A*0206, A*0207, A*6802, and A*6901. Finally, the B7-like supertype-confirmed alleles are: B7, B*3501-03, B51, B*5301, B*5401, B*5501-2, B*5601, B*6701, and B*7801 (potentially also B*1401, B*3504-06, B*4201, and B*5602). Population coverage achieved by combining the A2-, A3- and B7-supertypes is approximately 86% in five major ethnic groups. Coverage may be extended by including peptides bearing the Al and A24 motifs. On average, Al is present in 12% and A24 in 29% of the population across five different major ethnic groups (Caucasian, North American Black, Chinese, Japanese, and Hispanic). Together, these alleles are represented with an average frequency of 39% in these same ethnic populations. The total coverage across the major ethnicities when Al and A24 are combined with the coverage of the A2-, A3- and B7-supertype alleles is >95%, see, e.g., Table IV (G). An analogous approach can be used to estimate population coverage achieved with combinations of class Il motif-bearing epitopes. Immunogenicity studies in humans (e.g., Bertoni et al., J. Clin, Invest. 100:503, 1997; Doolan et al., immunity 7:97, 1997; and Threlkeld et al., J. Immunol. 159:1648, 1997) have shown that highly cross-reactive binding peptides are almost always recognized as epitopes. The use of highly cross-reactive binding peptides is an important selection criterion in identifying candidate epitopes for inclusion in a vaccine that is immunogenic in a diverse population. With a sufficient number of epitopes (as disclosed herein and from the art), an average population coverage is WO 2004/098515 PCT/US2004/013568 104 predicted to be greater than 95% in each of five major ethnic populations. The game theory Monte Carlo simulation analysis, which is known in the art (see e.g., Osborne, M.J. and Rubinstein, A. "A course in game theory" MIT Press, 1994), can be used to estimate what percentage of the individuals in a population comprised of the Caucasian, North American Black, Japanese, Chinese, and Hispanic ethnic groups would recognize the vaccine epitopes described herein. A preferred percentage is 90%. A more preferred percentage is 95%. Example 19: CTL Recognition Of Endogenously Processed Antigens After Priming This example confirms that CTL induced by native or analoged peptide epitopes identified and selected as described herein recognize endogenously synthesized, i.e., native antigens. Effector cells isolated from transgenic mice that are immunized with peptide epitopes, for example HLA-A2 supermotif-bearing epitopes, are re-stimulated in vitro using peptide-coated stimulator cells. Six days later, effector cells are assayed for cytotoxicity and the cell lines that contain peptide-specific cytotoxic activity are further re-stimulated. An additional six days later, these cell lines are tested for cytotoxic activity on 5 1Cr labeled Jurkat-A2.1/Kb target cells in the absence or presence of peptide, and also tested on 5 1 Cr labeled target cells bearing the endogenously synthesized antigen, i.e. cells that are stably transfected with 109P1 D4 expression vectors. The results demonstrate that CTL lines obtained from animals primed with peptide epitope recognize endogenously synthesized 109P1D4 antigen. The choice of transgenic mouse model to be used for such an analysis depends upon the epitope(s) that are being evaluated. In addition to HLA-A*0201/Kb transgenic mice, several other transgenic mouse models including mice with human Al1, which may also be used to evaluate A3 epitopes, and B7 alleles have been characterized and others (e.g., transgenic mice for HLA-Al and A24) are being developed. HLA-DR1 and HLA DR3 mouse models have also been developed, which may be used to evaluate HTL epitopes. Example 20: Activity Of CTL-HTL Conjugated Epitopes In Transgenic Mice This example illustrates the induction of CTLs and HTLs in transgenic mice, by use of a 109P1 D4-derived CTL and HTL peptide vaccine compositions. The vaccine composition used herein comprise peptides to be administered to a patient with a 109P1D4-expressing tumor. The peptide composition can comprise multiple CTL and/or HTL epitopes. The epitopes are identified using methodology as described herein. This example also illustrates that enhanced immunogenicity can be achieved by inclusion of one or more HTL epitopes in a CTL vaccine composition; such a peptide composition can comprise an HTL epitope conjugated to a CTL epitope. The CTL epitope can be one that binds to multiple HLA family members at an affinity of 500 nM or less, or analogs of that epitope. The peptides may be lipidated, if desired. Immunization procedures: Immunization of transgenic mice is performed as described (Alexander et al., J. Immunol. 159:4753-4761, 1997). For example, A2/Kb mice, which are transgenic for the human HLA A2.1 allele and are used to confirm the immunogenicity of HLA-A*0201 motif- or HLA-A2 supermotif-bearing epitopes, and are primed subcutaneously (base of the tail) with a 0.1 ml of peptide in Incomplete Freund's Adjuvant, or if the peptide composition is a lipidated CTL/HTL conjugate, in DMSO/saline, or if the peptide composition is a polypeptide, in PBS or Incomplete Freund's Adjuvant. Seven days after priming, splenocytes obtained from these animals are restimulated with syngenic irradiated LPS activated lymphoblasts coated with peptide. Cell lines: Target cells for peptide-specific cytotoxicity assays are Jurkat cells transfected with the HLA-A2.1/Kb chimeric gene (e.g., Vitiello et al., J. Exp. Med. 173:1007, 1991) In vitro CTL activation: One week after priming, spleen cells (30x1 06 cells/flask) are co-cultured at 37 0 C with syngeneic, irradiated (3000 rads), peptide coated lymphoblasts (10x106 cells/flask) in 10 ml of culture medium/T25 flask.

WO 2004/098515 PCT/US2004/013568 105 After six days, effector cells are harvested and assayed for cytotoxic activity. Assay for cytotoxic activity: Target cells (1.0 to 1.5x1 06) are incubated at 37*C in the presence of 200 pl of 5 1 Cr. After 60 minutes, cells are washed three times and resuspended in R10 medium. Peptide is added where required at a concentration of I pg/ml. For the assay, 104 51 Cr-labeled target cells are added to different concentrations of effector cells (final volume of 200 pl) in U-bottom 96-well plates. After a six hour incubation period at 37*C, a 0.1 ml aliquot of supernatant is removed from each well and radioactivity is determined in a Micromedic automatic gamma counter. The percent specific lysis is determined by the formula: percent specific release = 100 x (experimental release - spontaneous release)/(maximum release - spontaneous release). To facilitate comparison between separate CTL assays run under the same conditions, % 5 1 Cr release data is expressed as lytic units/106 cells. One lytic unit is arbitrarily defined as the number of effector cells required to achieve 30% lysis of 10,000 target cells in a six hour 5 1 Cr release assay. To obtain specific lytic units/1 06, the lytic units/1 06 obtained in the absence of peptide is subtracted from the lytic units/106 obtained in the presence of peptide. For example, if 30% 51 Cr release is obtained at the effector (E): target (T) ratio of 50:1 (i.e., 5x1 05 effector cells for 10,000 targets) in the absence of peptide and 5:1 (i.e., 5x10 4 effector cells for 10,000 targets) in the presence of peptide, the specific lytic units would be: [(1/50,000)-(1/500,000)] x 106 = 18 LU. The results are analyzed to assess the magnitude of the CTL responses of animals injected with the immunogenic CTLIHTL conjugate vaccine preparation and are compared to the magnitude of the CTL response achieved using, for example, CTL epitopes as outlined above in the Example entitled "Confirmation of Immunogenicity." Analyses similar to this may be performed to confirm the immunogenicity of peptide conjugates containing multiple CTL epitopes and/or multiple HTL epitopes. In accordance with these procedures, it is found that a CTL response is induced, and concomitantly that an HTL response is induced upon administration of such compositions. Example 21: Selection of CTL and HTL epitopes for inclusion in a 109P1ID4-specific vaccine. This example illustrates a procedure for selecting peptide epitopes for vaccine compositions of the invention. The peptides in the composition can be in the form of a nucleic acid sequence, either single or one or more sequences (i.e., minigene) that encodes peptide(s), or can be single and/or polyepitopic peptides. The following principles are utilized when selecting a plurality of epitopes for inclusion in a vaccine composition. Each of the following principles is balanced in order to make the selection. Epitopes are selected which, upon administration, mimic immune responses that are correlated with 109P1D4 clearance. The number of epitopes used depends on observations of patients who spontaneously clear 109P1 D4. For example, if it has been observed that patients who spontaneously clear 109P1 4-expressing cells generate an immune response to at least three (3) epitopes from 109P1 D4 antigen, then at least three epitopes should be included for HLA class I. A similar rationale is used to determine HLA class Il epitopes. Epitopes are often selected that have a binding affinity of an IC5o of 500 nM or less for an HLA class I molecule, or for class 11, an ICo of 1000 nM or less; or HLA Class I peptides with high binding scores from the BIMAS web site, at URL bimas.dcrt.nihgov/. In order to achieve broad coverage of the vaccine through out a diverse population, sufficient supermotif bearing peptides, or a sufficient array of allele-specific motif bearing peptides, are selected to give broad population coverage. In one embodiment, epitopes are selected to provide at least 80% population coverage. A Monte Carlo analysis, a statistical evaluation known in the art, can be employed to assess breadth, or redundancy, of population coverage. When creating polyepitopic compositions, or a minigene that encodes same, it is typically desirable to generate the smallest peptide possible that encompasses the epitopes of interest. The principles employed are similar, if not the same, as WO 2004/098515 PCT/US2004/013568 106 those employed when selecting a peptide comprising nested epitopes. For example, a protein sequence for the vaccine composition is selected because it has maximal number of epitopes contained within the sequence, i.e., it has a high concentration of epitopes. Epitopes may be nested or overlapping (i.e., frame shifted relative to one another). For example, with overlapping epitopes, two 9-mer epitopes and one 10-mer epitope can be present in a 10 amino acid peptide. Each epitope can be exposed and bound by an HLA molecule upon administration of such a peptide. A multi-epitopic, peptide can be generated synthetically, recombinantly, or via cleavage from the native source. Altematively, an analog can be made of this native sequence, whereby one or more of the epitopes comprise substitutions that alter the cross-reactivity and/or binding affinity properties of the polyepitopic peptide. Such a vaccine composition is administered for therapeutic or prophylactic purposes. This embodiment provides for the possibility that an as yet undiscovered aspect of immune system processing will apply to the native nested sequence and thereby facilitate the production of therapeutic or prophylactic immune response-inducing vaccine compositions. Additionally such an embodiment provides for the possibility of motif bearing epitopes for an HLA makeup that is presently unknown. Furthermore, this embodiment (absent the creating of any analogs) directs the immune response to multiple peptide sequences that are actually present in 109P1D4, thus avoiding the need to evaluate any junctional epitopes. Lastly, the embodiment provides an economy of scale when producing nucleic acid vaccine compositions. Related to this embodiment, computer programs can be derived in accordance with principles in the art, which identify in a target sequence, the greatest number of epitopes per sequence length. A vaccine composition comprised of selected peptides, when administered, is safe, efficacious, and elicits an immune response similar in magnitude to an immune response that controls or clears cells that bear or overexpress 109P1 D4. Example 22: Construction of "Minigene" Multi-Epitope DNA Plasmids This example discusses the construction of a minigene expression plasmid. Minigene plasmids may, of course, contain various configurations of B cell, CTL and/or HTL epitopes or epitope analogs as described herein. A minigene expression plasmid typically includes multiple CTL and HTL peptide epitopes. In the present example, HLA-A2, -A3, -B7 supermotif-bearing peptide epitopes and HLA-A1 and -A24 motif-bearing peptide epitopes are used in conjunction with DR supermotif-bearing epitopes and/or DR3 epitopes. HLA class I supermotif or motif-bearing peptide epitopes derived 109P1D4, are selected such that multiple supermotifs/motifs are represented to ensure broad population coverage. Similarly, HLA class I epitopes are selected from 109P1 D4 to provide broad population coverage, i.e. both HLA DR-1-4-7 supermotif-bearing epitopes and HLA DR-3 motif-bearing epitopes are selected for inclusion in the minigene construct. The selected CTL and HTL epitopes are then incorporated into a minigene for expression in an expression vector. Such a construct may additionally include sequences that direct the HTL epitopes to the endoplasmic reticulum. For example, the li protein may be fused to one or more HTL epitopes as described in the art, wherein the CLIP sequence of the Ii protein is removed and replaced with an HLA class 11 epitope sequence so that HLA class 11 epitope is directed to the endoplasmic reticulum, where the epitope binds to an HLA class Il molecules. This example illustrates the methods to be used for construction of a minigene-bearing expression plasmid. Other expression vectors that may be used for minigene compositions are available and known to those of skill in the art. The minigene DNA plasmid of this example contains a consensus Kozak sequence and a consensus murine kappa Ig-light chain signal sequence followed by CTL and/or HTL epitopes selected in accordance with principles disclosed herein. The sequence encodes an open reading frame fused to the Myc and His antibody epitope tag coded for by the pcDNA 3.1 Myc-His vector. Overlapping oligonucleotides that can, for example, average about 70 nucleotides in length with 15 nucleotide WO 2004/098515 PCT/US2004/013568 107 overlaps, are synthesized and HPLC-purifled. The oligonucleotides encode the selected peptide epitopes as well as appropriate linker nucleotides, Kozak sequence, and signal sequence. The final multiepitope minigene is assembled by extending the overlapping oligonucleotides in three sets of reactions using PCR. A Perkin/Elmer 9600 PCR machine is used and a total of 30 cycles are performed using the following conditions: 950C for 15 sec, annealing temperature (50 below the lowest calculated Tm of each primer pair) for 30 sec, and 72*C for 1 min. For example, a minigene is prepared as follows. For a first PCR reaction, 5 tg of each of two oligonucleotides are annealed and extended: In an example using eight oligonucleotides, i.e., four pairs of primers, oligonucleotides 1+2, 3+4, 5+6, and 7+8 are combined in 100 [ reactions containing Pfu polymerase buffer (1x= 10 mM KCL, 10 mM (NH4)2SO4, 20 mM Tris-chloride, pH 8.75, 2 mM MgSO4, 0.1% Triton X-100, 100 pg/ml BSA), 0.25 mM each dNTP, and 2.5 U of Pfu polymerase. The full-length dimer products are gel-purified, and two reactions containing the product of 1+2 and 3+4, and the product of 5+6 and 7+8 are mixed, annealed, and extended for 10 cycles. Half of the two reactions are then mixed, and 5 cycles of annealing and extension carried out before flanking primers are added to amplify the full length product. The full length product is gel-purified and cloned into pCR-blunt (Invitrogen) and individual clones are screened by sequencing. Example 23: The Plasmid Construct and the Degree to Which It Induces Immunogenicity. The degree to which a plasmid construct, for example a plasmid constructed in accordance with the previous Example, is able to induce immunogenicity is confirmed in vitro by determining epitope presentation by APC following transduction or transfection of the APC with an epitope-expressing nucleic acid construct. Such a study determines "antigenicity" and allows the use of human APC. The assay determines the ability of the epitope to be presented by the APC in a context that is recognized by a T cell by quantifying the density of epitope-HLA class I complexes on the cell surface. Quantitation can be performed by directly measuring the amount of peptide eluted from the APC (see, e.g., Sijts et al., J. Immunol. 156:683-692, 1996; Demotz et al., Nature 342:682-684, 1989); or the number of peptide-HLA class I complexes can be estimated by measuring the amount of lysis or lymphokine release induced by diseased or transfected target cells, and then determining the concentration of peptide necessary to obtain equivalent levels of lysis or lymphokine release (see, e.g., Kageyama et a., J. Immunol. 154:567-576, 1995). Alternatively, immunogenicity is confirmed through in vivo injections into mice and subsequent in vitro assessment of CTL and HTL activity, which are analyzed using cytotoxicity and proliferation assays, respectively, as detailed e.g., in Alexander eta., Immunity 1:751-761, 1994. For example, to confirm the capacity of a DNA minigene construct containing at least one HLA-A2 supermotif peptide to induce CTLs in vivo, HLA-A2.1/Kb transgenic mice, for example, are immunized intramuscularly with 100 ptg of naked cDNA. As a means of comparing the level of CTLs induced by cDNA immunization, a control group of animals is also immunized with an actual peptide composition that comprises multiple epitopes synthesized as a single polypeptide as they would be encoded by the minigene. Splenocytes from immunized animals are stimulated twice with each of the respective compositions (peptide epitopes encoded in the minigene or the polyepitopic peptide), then assayed for peptide-specific cytotoxic activity in a 51 Cr release assay. The results indicate the magnitude of the CTL response directed against the A2-restricted epitope, thus indicating the in vivo immunogenicity of the minigene vaccine and polyepitopic vaccine. It is, therefore, found that the minigene elicits immune responses directed toward the HLA-A2 supermotif peptide epitopes as does the polyepitopic peptide vaccine. A similar analysis is also performed using other HLA-A3 and HLA-B7 transgenic mouse models to assess CTL induction by HLA-A3 and HLA-B7 motif or supermotif epitopes, whereby it is also found that the minigene elicits appropriate immune responses directed toward the provided epitopes.

WO 2004/098515 PCT/US2004/013568 108 To confirm the capacity of a class 1i epitope-encoding minigene to induce HTLs in vivo, DR transgenic mice, or for those epitopes that cross react with the appropriate mouse MHC molecule, l-Ab-restricted mice, for example, are immunized intramuscularly with 100 ptg of plasmid DNA. As a means of comparing the level of HTLs induced by DNA immunization, a group of control animals is also immunized with an actual peptide composition emulsified in complete Freund's adjuvant. CD4+ T cells, i.e. HTLs, are purified from splenocytes of immunized animals and stimulated with each of the respective compositions (peptides encoded in the minigene). The HTL response is measured using a 3 H-thymidine incorporation proliferation assay, (see, e.g., Alexander et aL. Immunity 1:751-761, 1994). The results indicate the magnitude of the HTL response, thus demonstrating the in vivo immunogenicity of the minigene. DNA minigenes, constructed as described in the previous Example, can also be confirmed as a vaccine in combination with a boosting agent using a prime boost protocol. The boosting agent can consist of recombinant protein (e.g., Barnett et al, Aids Res. and Human Retroviruses 14, Supplement 3:S299-S309, 1998) or recombinant vaccinia, for example, expressing a minigene or DNA encoding the complete protein of interest (see, e.g., Hanke et al., Vaccine 16:439 445, 1998; Sedegah et al., Proc. Nat. Acad. Sci USA 95:7648-53, 1998; Hanke and McMichael, Immunol Letters 66:177 181, 1999; and Robinson et al., Nature Med. 5:526-34, 1999). For example, the efficacy of the DNA minigene used in a prime boost protocol is initially evaluated in transgenic mice. In this example, A2.1/Kb transgenic mice are immunized IM with 100 pig of a DNA minigene encoding the immunogenic peptides including at least one HLA-A2 supermotif-bearing peptide. After an incubation period (ranging from 3 9 weeks), the mice are boosted IP with 107 pfu/mouse of a recombinant vaccinia virus expressing the same sequence encoded by the DNA minigene. Control mice are immunized with 100 Ig of DNA or recombinant vaccinia without the minigene sequence, or with DNA encoding the minigene, but without the vaccinia boost. After an additional incubation period of two weeks, splenocytes from the mice are immediately assayed for peptide-specific activity in an ELISPOT assay. Additionally, splenocytes are stimulated in vitro with the A2-restricted peptide epitopes encoded in the minigene and recombinant vaccinia, then assayed for peptide-specific activity in an alpha, beta and/or gamma IFN ELISA. It is found that the minigene utilized in a prime-boost protocol elicits greater immune responses toward the HLA-A2 supermotif peptides than with DNA alone. Such an analysis can also be performed using HLA-A1 1 or HLA-B7 transgenic mouse models to assess CTL induction by HLA-A3 or HLA-B7 motif or supermotif epitopes. The use of prime boost protocols in humans is described below in the Example entitled "Induction of CTL Responses Using a Prime Boost Protocol." Example 24: Peptide Compositions for Prophylactic Uses Vaccine compositions of the present invention can be used to prevent 109P1D4 expression in persons who are at risk for tumors that bear this antigen, For example, a polyepitopic peptide epitope composition (or a nucleic acid comprising the same) containing multiple CTL and HTL epitopes such as those selected in the above Examples, which are also selected to target greater than 80% of the population, is administered to individuals at risk for a 109P1 D4-associated tumor. For example, a peptide-based composition is provided as a single polypeptide that encompasses multiple epitopes. The vaccine is typically administered in a physiological solution that comprises an adjuvant, such as Incomplete Freunds Adjuvant. The dose of peptide for the initial immunization is from about 1 to about 50,000 pag, generally 100-5,000 tg, for a 70 kg patient. The initial administration of vaccine is followed by booster dosages at 4 weeks followed by evaluation of the magnitude of the immune response in the patient, by techniques that determine the presence of epitope specific CTL populations in a PBMC sample. Additional booster doses are administered as required. The composition is found to be both safe and efficacious as a prophylaxis against 1 09P1 D4-associated disease. Alternatively, a composition typically comprising transfecting agents is used for the administration of a nucleic acid- WO 2004/098515 PCT/US2004/013568 109 based vaccine in accordance with methodologies known in the art and disclosed herein. Example 25: Polyepitopic Vaccine Compositions Derived from Native 109P1D4 Sequences A native 109P1 D4 polyprotein sequence is analyzed, preferably using computer algorithms defined for each class I and/or class li supermotif or motif, to identify "relatively short" regions of the polyprotein that comprise multiple epitopes. The "relatively short" regions are preferably less in length than an entire native antigen. This relatively short sequence that contains multiple distinct or overlapping, "nested" epitopes can be used to generate a minigene construct. The construct is engineered to express the peptide, which corresponds to the native protein sequence. The "relatively short" peptide is generally less than 250 amino acids in length, often less than 100 amino acids in length, preferably less than 75 amino acids in length, and more preferably less than 50 amino acids in length. The protein sequence of the vaccine composition is selected because it has maximal number of epitopes contained within the sequence, i.e., it has a high concentration of epitopes. As noted herein, epitope motifs may be nested or overlapping (i.e., frame shifted relative to one another). For example, with overlapping epitopes, two 9-mer epitopes and one 1 0-mer epitope can be present in a 10 amino acid peptide. Such a vaccine composition is administered for therapeutic or prophylactic purposes. The vaccine composition will include, for example, multiple CTL epitopes from 109P1 D4 antigen and at least one HTL epitope. This polyepitopic native sequence is administered either as a peptide or as a nucleic acid sequence which encodes the peptide. Alternatively, an analog can be made of this native sequence, whereby one or more of the epitopes comprise substitutions that alter the cross-reactivity and/or binding affinity properties of the polyepitopic peptide. The embodiment of this example provides for the possibility that an as yet undiscovered aspect of immune system processing will apply to the native nested sequence and thereby facilitate the production of therapeutic or prophylactic immune response-inducing vaccine compositions. Additionally, such an embodiment provides for the possibility of motif bearing epitopes for an HLA makeup(s) that is presently unknown. Furthermore, this embodiment (excluding an analoged embodiment) directs the immune response to multiple peptide sequences that are actually present in native 109P1D4, thus avoiding the need to evaluate any junctional epitopes. Lastly, the embodiment provides an economy of scale when producing peptide or nucleic acid vaccine compositions. Related to this embodiment, computer programs are available in the art which can be used to identify in a target sequence, the greatest number of epitopes per sequence length. Example 26: Polyepitopic Vaccine Compositions from Multiple Antigens The 109P1 D4 peptide epitopes of the present invention are used in conjunction with epitopes from other target tumor-associated antigens, to create a vaccine composition that is useful for the prevention or treatment of cancer that expresses 109P1D4 and such other antigens. For example, a vaccine composition can be provided as a single polypeptide that incorporates multiple epitopes from 109P1D4 as well as tumor-associated antigens that are often expressed with a target cancer associated with 109P1 D4 expression, or can be administered as a composition comprising a cocktail of one or more discrete epitopes. Alternatively, the vaccine can be administered as a minigene construct or as dendritic cells which have been loaded with the peptide epitopes in vitro. Example 27: Use of peptides to evaluate an immune response Peptides of the invention may be used to analyze an immune response for the presence of specific antibodies, CTL or HTL directed to 109P1 D4. Such an analysis can be performed in a manner described by Ogg et al., Science 279:2103-2106, 1998. In this Example, peptides in accordance with the invention are used as a reagent for diagnostic or WO 2004/098515 PCT/US2004/013568 110 prognostic purposes, not as an immunogen. In this example highly sensitive human leukocyte antigen tetrameric complexes ("tetramers") are used for a cross sectional analysis of, for example, 109P1D4 HLA-A*0201-specific CTL frequencies from HLA A*0201-positive individuals at different stages of disease or following immunization comprising a 109P1D4 peptide containing an A*0201 motif. Tetrameric complexes are synthesized as described (Musey et al., N. Eng. J. Med. 337:1267, 1997). Briefly, purified HLA heavy chain (A*0201 in this example) and p2-microglobulin are synthesized by means of a prokaryotic expression system. The heavy chain is modified by deletion of the transmembrane-cytosolic tail and COOH-terminal addition of a sequence containing a BirA enzymatic biotinylation site. The heavy chain, p2-microglobulin, and peptide are refolded by dilution. The 45-kD refolded product is isolated by fast protein liquid chromatography and then biotinylated by BirA in the presence of biotin (Sigma, St. Louis, Missouri), adenosine 5' triphosphate and magnesium. Streptavidin-phycoerythrin conjugate is added in a 1:4 molar ratio, and the tetrameric product is concentrated to 1 mg/ml. The resulting product is referred to as tetramer phycoerythrin. For the analysis of patient blood samples, approximately one million PBMCs are centrifuged at 300g for 5 minutes and resuspended in 50 pl of cold phosphate-buffered saline. Tri-color analysis is performed with the tetramer-phycoerythrin, along with anti-CDB-Tricolor, and anti-CD38. The PBMCs are incubated with tetramer and antibodies on ice for 30 to 60 min and then washed twice before formaldehyde fixation. Gates are applied to contain >99.98% of control samples. Controls for the tetramers include both A*0201-negative individuals and A*0201-positive non-diseased donors. The percentage of cells stained with the tetramer is then determined by flow cytometry. The results indicate the number of cells in the PBMC sample that contain epitope-restricted CTLs, thereby readily indicating the extent of immune response to the 109PI D4 epitope, and thus the status of exposure to 109P1D4, or exposure to a vaccine that elicits a protective or therapeutic response. Example 28: Use of Peptide Epitopes to Evaluate Recall Responses The peptide epitopes of the invention are used as reagents to evaluate T cell responses, such as acute or recall responses, in patients. Such an analysis may be performed on patients who have recovered from 109P1D4-associated disease or who have been vaccinated with a 109P1D4 vaccine. For example, the class I restricted CTL response of persons who have been vaccinated may be analyzed. The vaccine may be any 109P1D4 vaccine. PBMC are collected from vaccinated individuals and HLA typed. Appropriate peptide epitopes of the invention that, optimally, bear supermotifs to provide cross-reactivity with multiple HLA supertype family members, are then used for analysis of samples derived from individuals who bear that HLA type. PBMC from vaccinated individuals are separated on Ficoll-Histopaque density gradients (Sigma Chemical Co., St. Louis, MO), washed three times in HBSS (GIBCO Laboratories), resuspended in RPMI-1640 (GIBCO Laboratories) supplemented with L-glutamine (2mM), penicillin (50UIml), streptomycin (50 pg/ml), and Hepes (10mM) containing 10% heat-inactivated human AB serum (complete RPMI) and plated using microculture formats. A synthetic peptide comprising an epitope of the invention is added at 10 pLg/ml to each well and HBV core 128-140 epitope is added at 1 pg/ml to each well as a source of T cell help during the first week of stimulation. In the microculture format, 4 x 101 PBMC are stimulated with peptide in 8 replicate cultures in 96-well round bottom plate in 100 pil/well of complete RPMI. On days 3 and 10, 100 pl of complete RPMI and 20 U/ml final concentration of rIL-2 are added to each well. On day 7 the cultures are transferred into a 96-well flat-bottom plate and restimulated with peptide, rlL-2 and 106 irradiated (3,000 rad) autologous feeder cells. The cultures are tested for cytotoxic activity on day 14. A positive CTL response requires two or more of the eight replicate cultures to display greater than 10% specific 51 Cr release, based on comparison with non-diseased control subjects as previously described (Rehermann, et a., Nature Med.

WO 2004/098515 PCT/US2004/013568 111 2:1104,1108,1996; Rehermann etal., J. Clin. Invest. 97:1655-1665, 1996; and Rehermann et al. J. Clin. Invest. 98:1432 1440,1996). Target cell lines are autologous and allogeneic EBV-transformed B-LCL that are either purchased from the American Society for Histocompatibility and immunogenetics (ASHi, Boston, MA) or established from the pool of patients as described (Gulihot, et al. J. Virol. 66:2670-2678, 1992). Cytotoxicity assays are performed in the following manner. Target cells consist of either allogeneic HLA-matched or autologous EBV-transformed B lymphoblastoid cell line that are incubated overnight with the synthetic peptide epitope of the invention at 10 pLM, and labeled with 100 pCI of 51 Cr (Amersham Corp., Arlington Heights, IL) for 1 hour after which they are washed four times with HBSS. Cytolytic activity is determined in a standard 4-h, split well "Cr release assay using U-bottomed 96 well plates containing 3,000 targets/well. Stimulated PBMC are tested at effector/target (E/T) ratios of 20-50:1 on day 14. Percent cytotoxicity is determined from the formula: 100 x [(experimental release-spontaneous release)/maximum release spontaneous release)]. Maximum release is determined by lysis of targets by detergent (2% Triton X-100; Sigma Chemical Co., St. Louis, MO). Spontaneous release is <25% of maximum release for all experiments. The results of such an analysis indicate the extent to which HLA-restricted CTL populations have been stimulated by previous exposure to 109P1D4 or a 109P1D4 vaccine. Similarly, Class il restricted HTL responses may also be analyzed. Purified PBMC are cultured in a 98-well flat bottom plate at a density of 1.5x1 05 cells/well and are stimulated with 10 Ig/ml synthetic peptide of the invention, whole 109P1D4 antigen, or PHA. Cells are routinely plated in replicates of 4-6 wells for each condition. After seven days of culture, the medium is removed and replaced with fresh medium containing 1OU/mi IL-2. Two days later, 1 paCi 3 H-thymidine is added to each well and incubation is continued for an additional 18 hours. Cellular DNA is then harvested on glass fiber mats and analyzed for 3 H-thymidine incorporation. Antigen-specific T cell proliferation is calculated as the ratio of 3

H

thymidine incorporation in the presence of antigen divided by the 3 H-thymidine incorporation in the absence of antigen. Example 29: Induction Of Specific CTL Response in Humans A human clinical trial for an immunogenic composition comprising CTL and HTL epitopes of the invention is set up as an IND Phase I, dose escalation study and carried out as a randomized, double-blind, placebo-controlled trial. Such a trial is designed, for example, as follows: A total of about 27 individuals are enrolled and divided into 3 groups: Group 1: 3 subjects are injected with placebo and 6 subjects are injected with 5 pg of peptide composition; Group 11: 3 subjects are injected with placebo and 6 subjects are injected with 50 pag peptide composition; Group I1: 3 subjects are injected with placebo and 6 subjects are injected with 500 tg of peptide composition. After 4 weeks following the first injection, all subjects receive a booster inoculation at the same dosage. The endpoints measured in this study relate to the safety and tolerability of the peptide composition as well as its immunogenicity. Cellular immune responses to the peptide composition are an index of the intrinsic activity of this the peptide composition, and can therefore be viewed as a measure of biological efficacy. The following summarize the clinical and laboratory data that relate to safety and efficacy endpoints. Safety: The incidence of adverse events is monitored in the placebo and drug treatment group and assessed in terms of degree and reversibility. Evaluation of Vaccine Efficacy: For evaluation of vaccine efficacy, subjects are bled before and after injection. Peripheral blood mononuclear cells are isolated from fresh heparinized blood by Ficoli-Hypaque density gradient WO 2004/098515 PCT/US2004/013568 112 centrifugation, aliquoted in freezing media and stored frozen. Samples are assayed for CTL and HTL activity. The vaccine is found to be both safe and efficacious. Example 30: Phase If Trials In Patients Expressing 109P1D4 Phase i trials are performed to study the effect of administering the CTL-HTL peptide compositions to patients having cancer that expresses 109P1 D4. The main objectives of the trial are to determine an effective dose and regimen for inducing CTLs in cancer patients that express 109P1 D4, to establish the safety of inducing a CTL and HTL response in these patients, and to see to what extent activation of CTLs improves the clinical picture of these patients, as manifested, e.g., by the reduction and/or shrinking of lesions. Such a study is designed, for example, as follows: The studies are performed in multiple centers. The trial design is an open-label, uncontrolled, dose escalation protocol wherein the peptide composition is administered as a single dose followed six weeks later by a single booster shot of the same dose. The dosages are 50, 500 and 5,000 micrograms per injection. Drug-associated adverse effects (severity and reversibility) are recorded. There are three patient groupings. The first group is injected with 50 micrograms of the peptide composition and the second and third groups with 500 and 5,000 micrograms of peptide composition, respectively. The patients within each group range in age from 21-65 and represent diverse ethnic backgrounds. All of them have a tumor that expresses 109P1D4. Clinical manifestations or antigen-specific T-cell responses are monitored to assess the effects of administering the peptide compositions. The vaccine composition is found to be both safe and efficacious in the treatment of 109P1D4 associated disease. Example 31: Induction of CTL Responses Using a Prime Boost Protocol A prime boost protocol similar in its underlying principle to that used to confirm the efficacy of a DNA vaccine in transgenic mice, such as described above in the Example entitled "The Plasmid Construct and the Degree to Which It Induces immunogenicity," can also be used for the administration of the vaccine to humans. Such a vaccine regimen can include an initial administration of, for example, naked DNA followed by a boost using recombinant virus encoding the vaccine, or recombinant protein/polypeptide or a peptide mixture administered in an adjuvant For example, the initial immunization may be performed using an expression vector, such as that constructed in the Example entitled "Construction of "Minigene" Multi-Epitope DNA Plasmids" in the form of naked nucleic acid administered IM (or SC or ID) in the amounts of 0.5-5 mg at multiple sites. The nucleic acid (0.1 to 1000 ig) can also be administered using a gene gun. Following an incubation period of 3-4 weeks, a booster dose is then administered. The booster can be recombinant fowlpox virus administered at a dose of 5-107 to 5x10 9 pfu. An alternative recombinant virus, such as an MVA, canarypox, adenovirus, or adeno-associated virus, can also be used for the booster, or the polyepitopic protein or a mixture of the peptides can be administered. For evaluation of vaccine efficacy, patient blood samples are obtained before immunization as well as at intervals following administration of the initial vaccine and booster doses of the vaccine. Peripheral blood mononuclear cells are isolated from fresh heparinized blood by Ficoll-Hypaque density gradient centrifugation, aliquoted in freezing media and stored frozen. Samples are assayed for CTL and HTL activity. Analysis of the results indicates that a magnitude of response sufficient to achieve a therapeutic or protective immunity against 109P1 D4 is generated. Example 32: Administration of Vaccine Compositions Using Dendritic Cells (DC) WO 2004/098515 PCT/US2004/013568 113 Vaccines comprising peptide epitopes of the invention can be administered using APCs, or "professional" APCs such as DC. In this example, peptide-pulsed DC are administered to a patient to stimulate a CTL response in vivo. In this method, dendritic cells are isolated, expanded, and pulsed with a vaccine comprising peptide CTL and HTL epitopes of the invention. The dendritic cells are infused back into the patient to elicit CTL and HTL responses in vivo. The induced CTL and HTL then destroy or facilitate destruction, respectively, of the target cells that bear the 109P1 D4 protein from which the epitopes in the vaccine are derived. For example, a cocktail of epitope-comprising peptides is administered ex vivo to PBMC, or isolated DC therefrom. A pharmaceutical to facilitate harvesting of DC can be used, such as ProgenipoetinTM (Monsanto, St. Louis, MO) or GM CSF/IL-4. After pulsing the DC with peptides, and prior to reinfusion into patients, the DC are washed to remove unbound peptides. As appreciated clinically, and readily determined by one of skill based on clinical outcomes, the number of DC reinfused into the patient can vary (see, e.g., Nature Med. 4:328, 1998; Nature Med. 2:52, 1996 and Prostate 32:272,1997). Although 2-50 x 106 DC per patient are typically administered, larger number of DC, such as 107 or 108 can also be provided. Such cell populations typically contain between 50-90% DC. In some embodiments, peptide-loaded PBMC are injected into patients without purification of the DC. For example, PBMC generated after treatment with an agent such as ProgenipoletinTM are injected into patients without purification of the DC. The total number of PBMC that are administered often ranges from 108 to 1010. Generally, the cell doses injected into patients is based on the percentage of DC in the blood of each patient, as determined, for example, by immunofluorescence analysis with specific anti-DC antibodies. Thus, for example, if ProgenipoietinTM mobilizes 2% DC in the peripheral blood of a given patient, and that patient is to receive 5 x 106 DC, then the patient will be injected with a total of 2.5 x 108 peptide-loaded PBMC. The percent DC mobilized by an agent such as Progenipoletin T M is typically estimated to be between 2-10%, but can vary as appreciated by one of skill in the art. Ex vivo activation of CTL/HTL responses Alternatively, ex vivo CTL or HTL responses to 109P1D4 antigens can be induced by incubating, in tissue culture, the patient's, or genetically compatible, CTL or HTL precursor cells together with a source of APC, such as DC, and immunogenic peptides. After an appropriate incubation time (typically about 7-28 days), in which the precursor cells are activated and expanded into effector cells, the cells are infused into the patient, where they will destroy (CTL) or facilitate destruction (HTL) of their specific target cells, i.e., tumor cells. Example 33: An Alternative Method of Identifying and Confirming Motif-Bearing Peptides Another method of identifying and confirming motif-bearing peptides is to elute them from cells bearing defined MHC molecules. For example, EBV transformed B cell lines used for tissue typing have been extensively characterized to determine which HLA molecules they express. In certain cases these cells express only a single type of HLA molecule. These cells can be transfected with nucleic acids that express the antigen of interest, e.g. 109P1D4. Peptides produced by endogenous antigen processing of peptides produced as a result of transfection will then bind to HLA molecules within the cell and be transported and displayed on the cell's surface. Peptides are then eluted from the HLA molecules by exposure to mild acid conditions and their amino acid sequence determined, e.g., by mass spectral analysis (e.g., Kubo et al., J. Immune. 152:3913, 1994). Because the majority of peptides that bind a particular HLA molecule are motif-bearing, this is an alternative modality for obtaining the motif-bearing peptides correlated with the particular HLA molecule expressed on the cell. Alternatively, cell lines that do not express endogenous HLA molecules can be transfected with an expression WO 2004/098515 PCT/US2004/013568 114 construct encoding a single HLA allele. These cells can then be used as described, i.e., they can then be transfected with nucleic acids that encode 109P1 D4 to isolate peptides corresponding to 109P1D4 that have been presented on the cell surface. Peptides obtained from such an analysis will bear motif(s) that correspond to binding to the single HLA allele that is expressed in the cell. As appreciated by one in the art, one can perform a similar analysis on a cell bearing more than one HLA allele and subsequently determine peptides specific for each HLA allele expressed. Moreover, one of skill would also recognize that means other than transfection, such as loading with a protein antigen, can be used to provide a source of antigen to the cell. Example 34: Complementary Polynucleotides Sequences complementary to the 109P1 D4-encoding sequences, or any parts thereof, are used to detect, decrease, or inhibit expression of naturally occurring 109P1 D4. Although use of oligonucleotides comprising from about 15 to 30 base pairs is described, essentially the same procedure is used with smaller or with larger sequence fragments. Appropriate oligonucleotides are designed using, e.g., OLIGO 4.06 software (National Biosciences) and the coding sequence of 109P1 D4. To inhibit transcription, a complementary oligonucleotide is designed from the most unique 5' sequence and used to prevent promoter binding to the coding sequence. To inhibit translation, a complementary oligonucleotide is designed to prevent ribosomal binding to a 109P1 D4-encoding transcript. Example 35: Purification of Naturally-occurring or Recombinant 109P1 D4 Using 109P1 D4-Specific Antibodies Naturally occurring or recombinant 109P1 D4 is substantially purified by immunoaffinity chromatography using antibodies specific for 109P1 D4. An immunoaffinity column is constructed by covalently coupling anti-1 09P1 D4 antibody to an activated chromatographic resin, such as CNBr-activated SEPHAROSE (Amersham Pharmacia Biotech). After the coupling, the resin is blocked and washed according to the manufacturer's instructions. Media containing 109P1 D4 are passed over the immunoaffinity column, and the column is washed under conditions that allow the preferential absorbance of 109P1D4 (e.g., high ionic strength buffers in the presence of detergent). The column is eluted under conditions that disrupt antibody/i 09P1 D4 binding (e.g., a buffer of pH 2 to pH 3, or a high concentration of a chaotrope, such as urea or thiocyanate ion), and GCR.P is collected. Example 36: Identification of Molecules Which Interact with 109P1 D4 109P1D4, or biologically active fragments thereof, are labeled with 121 1 Bolton-Hunter reagent. (See, e.g., Bolton et al. (1973) Biochem. J. 133:529.) Candidate molecules previously arrayed in the wells of a multi-well plate are incubated with the labeled 109P1 D4, washed, and any wells with labeled 109P1 D4 complex are assayed. Data obtained using different concentrations of 109PI D4 are used to calculate values for the number, affinity, and association of 109PI D4 with the candidate molecules. Example 37: In Vivo Assay for 109P1D4 Tumor Growth Promotion The effect of a 109P1D4 protein on tumor cell growth is evaluated in vivo by gene overexpression in tumor-bearing mice. For example, SCID mice are injected subcutaneously on each flank with 1 x 106 of either PC3, DU145 or 3T3 cells containing tkNeo empty vector or a nucleic acid sequence of the invention. At least two strategies can be used: (1) Constitutive expression under regulation of a promoter such as a constitutive promoter obtained from the genomes of viruses such as polyoma virus, fowipox virus (UK 2,211,504 published 5 July 1989), adenovirus (such as Adenovirus 2), bovine WO 2004/098515 PCT/US2004/013568 115 papilloma virus, avian sarcoma virus, cytomegalovirus, a retrovirus, hepatitis-B virus and Simian Virus 40 (SV40), or from heterologous mammalian promoters, e.g., the actin promoter or an immunoglobulin promoter, provided such promoters are compatible with the host cell systems, and (2) Regulated expression under control of an inducible vector system, such as ecdysone, tet, etc., provided such promoters are compatible with the host cell systems. Tumor volume is then monitored at the appearance of palpable tumors and followed over time to determine if the cells expressing a gene of the invention grow at a faster rate and whether tumors of a 109P1 D4 protein-expressing cells demonstrate characteristics of altered aggressiveness (e.g. enhanced metastasis, vascularization, reduced responsiveness to chemotherapeutic drugs). Additionally, mice can be implanted with 1 x 106 of the same cells orthotopically to determine if a protein of the invention has an effect on local growth in the prostate or on the ability of the cells to metastasize, specifically to lungs, lymph nodes, and bone marrow. The assay is also useful to determine the inhibitory effect of candidate therapeutic compositions, such as for example, 109P1D4 protein-related intrabodies, 109P1D4 gene-related antisense molecules and ribozymes. Example 38: 109P1 D4 Monoclonal Antibody-mediated Inhibition of Tumors In Vivo The significant expression of I 09P1 D4 proteins in the cancer tissues of Table I and its restrictive expression in normal tissues, together with its expected cell surface expression, makes 109P1 D4 proteins excellent targets for antibody therapy. Similarly, 109P1 D4 proteins are a target for T cell-based immunotherapy. Thus, for 109P1 D4 genes expressed, e.g., in prostate cancer, the therapeutic efficacy of anti-I 09P1D4 protein mAbs in human prostate cancer xenograft mouse models is evaluated by using androgen-independent LAPC-4 and LAPC-9 xenografts (Craft, N., et al.,. Cancer Res, 1999. 59(19): p. 5030-6) and the androgen independent recombinant cell line PC3-of 109P1D4 (see, e.g., Kaighn, M.E., et al., Invest Urol, 1979. 17(1): p. 16-23); analogous models are used for other cancers. Antibody efficacy on tumor growth and metastasis formation is studied, e.g., in a mouse orthotopic prostate cancer xenograft models and mouse kidney xenograft models. The antibodies can be unconjugated, as discussed in this Example, or can be conjugated to a therapeutic modality, as appreciated in the art. Anti-i 09P1D4 protein mAbs inhibit formation of both the androgen-dependent LAPC-9 and androgen-independent PC3-109P1D4 protein tumor xenografts. Anti-109P1D4 protein mAbs also retard the growth of established orthotopic tumors and prolonged survival of tumor-bearing mice. These results indicate the utility of anti-I 09P1D4 protein mAbs in the treatment of local and advanced stages of prostate cancer. (See, e.g., (Saffran, D., et al., PNAS 10:1073-1078 or World Wide Web URL ww.pnas.org/cgi/doi/10.1073/pnas.051624698). Administration of the anti-i 09P1 D4 protein mAbs lead to retardation of established orthotopic tumor growth and inhibition of metastasis to distant sites, resulting in a significant prolongation in the survival of tumor-bearing mice. These studies indicate that proteins of the invention are attractive targets for immunotherapy and demonstrate the therapeutic potential of anti-1 09P1D4 protein mAbs for the treatment of local and metastatic cancer. This example demonstrates that unconjugated 109P1D4 protein-related monoclonal antibodies are effective to inhibit the growth of human prostate tumor xenografts and human kidney xenografts grown in SCID mice; accordingly a combination of such efficacious monoclonal antibodies is also effective. Tumor inhibition using multiple unconjugated mAbs Materials and Methods I09PID4 Protein-related Monoclonal Antibodies: Monoclonal antibodies are raised against proteins of the invention as described in the Example entitled "Generation of 109P1D4 Monoclonal Antibodies". The antibodies are characterized by ELISA, Western blot, FACS, and WO 2004/098515 PCT/US2004/013568 116 immunoprecipitation for their capacity to bind to the respective protein of the invention. Epitope mapping data for, e.g., the anti-1 09P1 D4 protein mAbs, as determined by ELISA and Western analysis, indicate that the antibodies recognize epitopes on the respective 109P1D4 protein. Immunohistochemical analysis of prostate cancer tissues and cells with these antibodies is performed. The monoclonal antibodies are purified from ascites or hybridoma tissue culture supematants by Protein-G Sepharose chromatography, dialyzed against PBS, filter sterilized, and stored at -20*C. Protein determinations are performed by a Bradford assay (Bio-Rad, Hercules, CA). A therapeutic monoclonal antibody or a cocktail comprising a mixture of individual monoclonal antibodies is prepared and used for the treatment of mice receiving subcutaneous or orthotopic injections of LAPC-9 prostate tumor xenografts. Cancer Xenografts and Cell Lines The LAPC-9 xenograft, which expresses a wild-type androgen receptor and produces prostate-specific antigen (PSA), is passaged in 6- to 8-week-old male ICR-severe combined immunodeficient (SCID) mice (Taconic Farms) by s.c. trocar implant (Craft, N., et at., supra). The prostate carcinoma cell line PC3 (American Type Culture Collection) is maintained in RPMI supplemented with L-glutamine and 10% FBS. Recombinant PC3 and 3T3- cell populations expressing a protein of the invention are generated by retroviral gene transfer as described in Hubert, R.S., et al., STEAP: a prostate-specific cell-surface antigen highly expressed in human prostate tumors. Proc Nati Acad Sci U S A, 1999. 96(25): p. 14523-8. Anti-protein of the invention staining is detected by using an FITC-conjugated goat anti-mouse antibody (Southern Biotechnology Associates) followed by analysis on a Coulter Epics-XL flow cytometer. Xenograft Mouse Models. Subcutaneous (s.c.) tumors are generated by injection of 1 x 10 6 LAPC-9, PC3, recombinant PC3-protein of the invention, 3T3 or recombinant 3T3-protein of the invention cells mixed at a 1:1 dilution with Matrigel (Collaborative Research) in the right flank of male SCID mice. To test antibody efficacy on tumor formation, i.p. antibody injections are started on the same day as tumor-cell injections. As a control, mice are injected with either purified mouse IgG (ICN) or PBS; or a purified monoclonal antibody that recognizes an irrelevant antigen not expressed in human cells. In preliminary studies, no difference is found between mouse igG or PBS on tumor growth. Tumor sizes are determined by vernier caliper measurements, and the tumor volume is calculated as length x width x height. Mice with s.c. tumors greater than 1.5 cm in diameter are sacrificed. PSA levels are determined by using a PSA ELISA kit (Anogen, Mississauga, Ontario). Circulating levels of, e.g., anti-109PI D4 protein mAbs are determined by a capture ELISA kit (Bethyl Laboratories, Montgomery, TX). (See, e.g., Saffran, D., et al., PNAS 10:1073-1078 or www.pnas.org/cgi/ dol/I0.1073/pnas.051624698) Orthotopic injections are performed under anesthesia by using ketamine/xylazine. For prostate orthotopic studies, an incision is made through the abdominal muscles to expose the bladder and seminal vesicles, which then are delivered through the incision to expose the dorsal prostate. LAPC-9 or PC3 cells (5 x 105) mixed with Matrigel are injected into each dorsal lobe in a 10-pl volume. To monitor tumor growth, mice are bled on a weekly basis for determination of PSA levels. The mice are segregated into groups for the appropriate treatments, with anti-protein of the invention or control mAbs being injected i.p. Anti-109P1 D4 Protein mAbs Inhibit Growth of Respective 109P1D4 Protein-Expressino Xenograft-Cancer Tumors The effect of anti-109P1D4 protein mAbs on tumor formation is tested by using LAPC-9 and recombinant PC3 protein of the invention orthotopic models. As compared with the s.c. tumor model, the orthotopic model, which requires injection of tumor cells directly in the mouse prostate or kidney, respectively, results in a local tumor growth, development of metastasis in distal sites, deterioration of mouse health, and subsequent death (Saffran, D., et al., PNAS supra; Fu, X., et al., WO 2004/098515 PCT/US2004/013568 117 Int J Cancer, 1992. 52(6): p. 987-90; Kubota, T., J Cell Biochem, 1994. 56(1): p. 4-8). The features make the orthotopic model more representative of human disease progression and allowed us to follow the therapeutic effect of mAbs on clinically relevant end points. Accordingly, tumor cells are injected into the mouse prostate or kidney, and 2 days later, the mice are segregated into two groups and treated with either: a) 200-500pg, of anti-I 09P1 D4 protein Ab, or b) PBS three times per week for two to five weeks. A major advantage of the orthotopic prostate-cancer model is the ability to study the development of metastases. Formation of metastasis in mice bearing established orthotopic tumors is studied by IHC analysis on lung sections using an antibody against a prostate-specific cell-surface protein STEAP expressed at high levels in LAPC-9 xenografts (Hubert, R.S., et al., Proc Nati Acad Sci U S A, 1999. 96(25): p. 14523-8). Mice bearing established orthotopic LAPC-9 or recombinant PC3-109P1D4 protein tumors are administered 10O0pg injections of either anti-I 09P1 D4 protein mAbs or PBS over a 4-week period. Mice in both groups are allowed to establish a high tumor burden (PSA levels greater than 300 ng/ml for IAPC-9), to ensure a high frequency of metastasis formation in mouse lungs. Mice then are killed and their prostate and lungs are analyzed for the presence of tumor cells by IHC analysis. These studies demonstrate a broad anti-tumor efficacy of anti-1 09P1 D4 protein antibodies on initiation and progression of prostate cancer in xenograft mouse models. Anti-1 09P1 D4 protein antibodies inhibit tumor formation of both androgen-dependent and androgen-independent tumors, retard the growth of already established tumors, and prolong the survival of treated mice. Moreover, anti-I 09P1 D4 protein mAbs demonstrate a dramatic inhibitory effect on the spread of local prostate tumor to distal sites, even in the presence of a large tumor burden. Thus, anti-1 09P1 D4 protein mAbs are efficacious on major clinically relevant end points (tumor growth), prolongation of survival, and health. Example 39: Therapeutic and Diagnostic use of Anti-109P1D4 Antibodies in Humans. Anti-I 09P1 D4 monoclonal antibodies are safely and effectively used for diagnostic, prophylactic, prognostic and/or therapeutic purposes in humans. Western blot and immunohistochemical analysis of cancer tissues and cancer xenografts with anti-1 09P1 D4 mAb show strong extensive staining in carcinoma but significantly lower or undetectable levels in normal tissues. Detection of 109P1 D4 in carcinoma and in metastatic disease demonstrates the usefulness of the mAb as a diagnostic andlor prognostic indicator. Anti-I 09P1 D4 antibodies are therefore used in diagnostic applications such as immunohistochemistry of kidney biopsy specimens to detect cancer from suspect patients. As determined by flow cytometry, anti-109P1D4 mAb specifically binds to carcinoma cells. Thus, anti-109P1D4 antibodies are used in diagnostic whole body imaging applications, such as radioimmunoscintigraphy and radioimmunotherapy, (see, e.g., Potamianos S., et. al. Anticancer Res 20(2A):925-948 (2000)) for the detection of localized and metastatic cancers that exhibit expression of 109P1D4. Shedding or release of an extracellular domain of 109P1D4 into the extracellular milieu, such as that seen for alkaline phosphodiesterase BI0 (Meerson, N. R., Hepatology 27:563-568 (1998)), allows diagnostic detection of 109P1D4 by anti-109P1D4 antibodies in serum and/or urine samples from suspect patients. Anti-i09P1D4 antibodies that specifically bind 109P1D4 are used in therapeutic applications for the treatment of cancers that express 109P1D4. Anti-109P1D4 antibodies are used as an unconjugated modality and as conjugated form in which the antibodies are attached to one of various therapeutic or imaging modalities well known in the art, such as a prodrugs, enzymes or radioisotopes, In preclinical studies, unconjugated and conjugated anti-109P1D4 antibodies are tested for efficacy of tumor prevention and growth inhibition in the SCID mouse cancer xenograft models, e.g., kidney cancer WO 2004/098515 PCT/US2004/013568 118 models AGS-K3 and AGS-K6, (see, e.g., the Example entitled '109P1D4 Monoclonal Antibody-mediated Inhibition of Bladder and Lung Tumors In Vivo"). Either conjugated and unconjugated anti-i 09P1 D4 antibodies are used as a therapeutic modality in human clinical trials either alone or in combination with other treatments as described in following Examples. Example 40: Human Clinical Trials for the Treatment and Diagnosis of Human Carcinomas through use of Human Anti-i 09P1 D4 Antibodies In vivo Antibodies are used in accordance with the present invention which recognize an epitope on 109P1 D4, and are used in the treatment of certain tumors such as those listed in Table I. Based upon a number of factors, including 109P1D4 expression levels, tumors such as those listed in Table I are presently preferred indications. In connection with each of these indications, three clinical approaches are successfully pursued. I.) Adjunctive therapy: In adjunctive therapy, patients are treated with anti-109P1D4 antibodies in combination with a chemotherapeutic or antineoplastic agent and/or radiation therapy. Primary cancer targets, such as those listed in Table I, are treated under standard protocols by the addition anti-i 09P1 D4 antibodies to standard first and 'second line therapy. Protocol designs address effectiveness as assessed by reduction in tumor mass as well as the ability to reduce usual doses of standard chemotherapy. These dosage reductions allow additional andfor prolonged therapy by reducing dose-related toxicity of the chemotherapeutic agent. Anti-1 09P1D4 antibodies are utilized in several adjunctive clinical trials in combination with the chemotherapeutic or antineoplastic agents adriamycin (advanced prostrate carcinoma), cisplatin (advanced head and neck and lung carcinomas), taxol (breast cancer), and doxorubicin (preclinical). 11.) Monotherapy: In connection with the use of the anti-109P1D4 antibodies in monotherapy of tumors, the antibodies are administered to patients without a chemotherapeutic or antineoplastic agent. in one embodiment, monotherapy is conducted clinically in end stage cancer patients with extensive metastatic disease. Patients show some disease stabilization. Trials demonstrate an effect in refractory patients with cancerous tumors. Ill.) Imaging Agent: Through binding a radionuclide (e.g., iodine or yttrium (1131, YGO) to anti-109P1 D4 antibodies, the radiolabeled antibodies are utilized as a diagnostic and/or imaging agent. In such a role, the labeled antibodies localize to both solid tumors, as well as, metastatic lesions of cells expressing 109P1 D4. In connection with the use of the anti-I 09P1 4 antibodies as imaging agents, the antibodies are used as an adjunct to surgical treatment of solid tumors, as both a pre-surgical screen as well as a post-operative follow-up to determine what tumor remains and/or returns. In one embodiment, a (111 In)-109P11D4 antibody is used as an imaging agent in a Phase I human clinical trial in patients having a carcinoma that expresses 109P1D4 (by analogy see, e.g., Divgi et al. J. Nati. Cancer Inst. 83:97-104 (1991)). Patients are followed with standard anterior and posterior gamma camera. The results indicate that primary lesions and metastatic lesions are identified. Dose and Route of Administration As appreciated by those of ordinary skill in the art, dosing considerations can be determined through comparison with the analogous products that are in the clinic. Thus, anti-1 09P1D4 antibodies can be administered with doses in the range of 5 to 400 mg/m 2, with the lower doses used, e.g., in connection with safety studies. The affinity of anti-109P1D4 antibodies relative to the affinity of a known antibody for its target is one parameter used by those of skill in the art for determining analogous dose regimens. Further, anti-I 09P1 D4 antibodies that are fully human antibodies, as compared to the chimeric antibody, have slower clearance; accordingly, dosing in patients with such fully human anti-1 09P1 D4 antibodies can be lower, perhaps in the range of 50 to 300 mg/im 2 , and still remain efficacious. Dosing in mg/m 2 , as opposed to the conventional measurement of dose in mg/kg, is a measurement based on surface area and is a convenient dosing measurement that is designed to include patients of all sizes from infants to adults.

WO 2004/098515 PCT/US2004/013568 119 Three distinct delivery approaches are useful for delivery of anti-109PiD4 antibodies. Conventional intravenous delivery is one standard delivery technique for many tumors. However, in connection with tumors in the peritoneal cavity, such as tumors of the ovaries, biliary duct, other ducts, and the like, intraperitoneal administration may prove favorable for obtaining high dose of antibody at the tumor and to also minimize antibody clearance. In a similar manner, certain solid tumors possess vasculature that is appropriate for regional perfusion. Regional perfusion allows for a high dose of antibody at the site of a tumor and minimizes short term clearance of the antibody. Clinical Development Plan (CDP) Overview: The CDP follows and develops treatments of anti-I 09P1D4 antibodies in connection with adjunctive therapy, monotherapy, and as an imaging agent. Trials initially demonstrate safety and thereafter confirm efficacy in repeat doses. Trails are open label comparing standard chemotherapy with standard therapy plus anti-109P1D4 antibodies. As will be appreciated, one criteria that can be utilized in connection with enrollment of patients is 109P1 D4 expression levels in their tumors as determined by biopsy. As with any protein or antibody infusion-based therapeutic, safety concerns are related primarily to (i) cytokine release syndrome, i.e., hypotension, fever, shaking, chills; (ii) the development of an immunogenic response to the material (i.e., development of human antibodies by the patient to the antibody therapeutic, or HAHA response); and, (iii) toxicity to normal cells that express 109P1D4. Standard tests and follow-up are utilized to monitor each of these safety concerns. Anti-1 09P1D4 antibodies are found to be safe upon human administration. Example 41: Human Clinical Trial Adjunctive Therapy with Human Anti-109P1D4 Antibody and Chemotherapeutic Agent A phase I human clinical trial is initiated to assess the safety of six intravenous doses of a human anti-1 09P1 D4 antibody in connection with the treatment of a solid tumor, e.g., a cancer of a tissue listed in Table I. In the study, the safety of single doses of anti-1 09P1 D4 antibodies when utilized as an adjunctive therapy to an antineoplastic or chemotherapeutic agent as defined herein, such as, without limitation: cisplatin, topotecan, doxorubicin, adriamycin, taxol, or the like, is assessed. The trial design includes delivery of six single doses of an anti-109P1D4 antibody with dosage of antibody escalating from approximately about 25 mg/m 2 to about 275 mg/m o ver the course of the treatment in accordance with the following schedule: Day 0 Day 7 Day 14 Day 21 Day 28 Day 35 mAb Dose 25 75 125 175 225 275 mg/m 2 mg/m 2 mg/m 2 mg/m 2 mg/m 2 mg/m 2 Chemotherapy + + + + + + (standard dose) Patients are closely followed for one-week following each administration of antibody and chemotherapy. In particular, patients are assessed for the safety concerns mentioned above: (i) cytokine release syndrome, i.e., hypotension, fever, shaking, chills; (ii) the development of an immunogenic response to the material (i.e., development of human antibodies by the patient to the human antibody therapeutic, or HAHA response); and, (iii) toxicity to normal cells that express 109P1 D4. Standard tests and follow-up are utilized to monitor each of these safety concerns. Patients are also assessed for clinical outcome, and particularly reduction in tumor mass as evidenced by MRI or other imaging.

WO 2004/098515 PCT/US2004/013568 120 The anti-I 09P1 D4 antibodies are demonstrated to be safe and efficacious, Phase Il trials confirm the efficacy and refine optimum dosing. Example 42: Human Clinical Trial: Monotherapy with Human Anti-109P1D4 Antibody Anti-I09P1D4 antibodies are safe in connection with the above-discussed adjunctive trial, a Phase II human clinical trial confirms the efficacy and optimum dosing for monotherapy. Such trial is accomplished, and entails the same safety and outcome analyses, to the above-described adjunctive trial with the exception being that patients do not receive chemotherapy concurrently with the receipt of doses of anti-I 09P1 D4 antibodies. Example 43: Human Clinical Trial: Diagnostic Imaging with Anti-109P1D4 Antibody Once again, as the adjunctive therapy discussed above is safe within the safety criteria discussed above, a human clinical trial is conducted concerning the use of anti-109P1D4 antibodies as a diagnostic imaging agent. The protocol is designed in a substantially similar manner to those described in the art, such as in Divgi et aL. J. Nati. Cancer Inst. 83:97-104 (1991). The antibodies are found to be both safe and efficacious when used as a diagnostic modality. Example 44: 109P1D4 Functional Assays 1. Phosphorylation of 109P1D4 on tyrosine residues One hallmark of the cancer cell phenotype is the active signal transduction of surface bound receptor molecules, such as the EGF receptor, through tyrosine phosphorylation of their cytoplasmic domains and their subsequent interaction with cytosolic signaling molecules. To address the possibility that I 09P1 D4 is phosphorylated on its cytoplamsic tyrosine residues, 293T cells were transfected with the 109P1 D4 gene in an expression plasmid such that the 109P1 D4 gene was fused with a Myc/His tag, and were then stimulated with pervanadate (a 1:1 mixture of Na3VO4 and H202). After solubilization of the cells in Triton X-100, the 109P1D4 protein was immunoprecipitated with anti-His polyclonal antibody (pAb), subjected to SDS-PAGE and Western blotted with anti-phosphotyrosine. Equivalent immunoprecipitates were Western blotted with anti-His antibody. In Figure 22, 109P1D4 exhibits tyrosine phosphorylation only upon cell treatment with pervanadate and not without treatment. This suggests that pervanadate, which inhibits intracellular protein tyrosine phosphatases (PTPs), allows the accumulation of phosphotyrosine (tyrosine kinase activity) on 109P1D4. Further, a large amount of the 109P1D4 protein is sequestered into the insoluble fraction upon pervanadate activation, suggesting its association with cytoskeletal components. Similar effects of partial insolubility in Triton X-100 have been observed for cadherins, proteins that are related to protocadherins based on homology of their extracellular domains. Cadherins are known to interact with cytoskeletal proteins including actin, which are not readily soluble in the detergent conditions used in this study. Together, these data indicate that 109P1D4 is a surface receptor with the capacity to be phosphorylated on tyrosine and to bind to signaling molecules that possess SH2 or PTB binding domains, including but not limited to, phospholipase-Cyl, Grb2, Shc, Crk, PI-3-kinase p85 subunit, rasGAP, Src-family kinases and abl-family kinases. Such interactions are important for downstream signaling through 109P1 D4, leading to changes in adhesion, proliferation, migration or elaboration of secreted factors, In addition, I 09P1 D4 protein interacts with cytoskeletal components such as actin that facilitates its cell adhesion functions. These phenotypes are enhanced in I 09P1 D4 expressing tumor cells and contribute to their increased capacity to metastasize and grow in vivo. Thus, when 109P1 D4 plays a role in cell signaling and phosphorylation, it is used as a target for diagnostic, prognostic, preventative and/or therapeutic purposes. Example 45: 109P1D4 RNA Interference (RNAi) WO 2004/098515 PCT/US2004/013568 121 RNA interference (RNAi) technology is implemented to a variety of cell assays relevant to oncology. RNAi is a post-transcriptional gene silencing mechanism activated by double-stranded RNA (dsRNA). RNAi induces specific mRNA degradation leading to changes in protein expression and subsequently in gene function. In mammalian cells, these dsRNAs called short interfering RNA (siRNA) have the correct composition to activate the RNAi pathway targeting for degradation, specifically some mRNAs. See, Elbashir S.M., ei. al., Duplexes of 21-nucleotide RNAs Mediate RNA interference in Cultured Mammalian Cells, Nature 411(6836):494-8 (2001). Thus, RNAi technology is used successfully in mammalian cells to silence targeted genes. Loss of cell proliferation control is a hallmark of cancerous cells; thus, assessing the role of 109PI D4 in cell survival/proliferation assays is relevant. Accordingly, RNAi was used to investigate the function of the I 09P1 D4 antigen. To generate siRNA for 109P1 D4, algorithms were used that predict oligonucleotides that exhibit the critical molecular parameters (G:C content, melting temperature, etc.) and have the ability to significantly reduce the expression levels of the 109P1D4 protein when introduced into cells. Accordingly, three targeted sequences for the 109P1D4 siRNA are: 5' AAGAGGATACTGGTGAGATCT 3' (SEQ ID NO: 57)(oligo 109P1D4.a), 5' AAGAGCAATGGTGCTGGTAAA 3' (SEQ ID NO: 58)(oligo 109P1D4.c), and 5' AACACCAGAAGGAGACAAGAT3' (SEQ ID NO: 59)(oligo 109P1D4.d). In accordance with this Example, 109P1 D4 siRNA compositions are used that comprise siRNA (double stranded, short interfering RNA) that correspond to the nucleic acid ORF sequence of the 109P1 D4 protein or subsequences thereof. Thus, siRNA subsequences are used in this manner are generally 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30,31, 32, 33, 34, 35 or more than 35 contiguous RNA nucleotides in length. These siRNA sequences are complementary and non-complementary to at least a portion of the mRNA coding sequence. In a preferred embodiment, the subsequences are 19-25 nucleotides in length, most preferably 21-23 nucleotides in length. In preferred embodiments, these siRNA achieve knockdown of 109P1 D4 antigen in cells expressing the protein and have functional effects as described below. The selected siRNAs (109P1D4.a, 109P1D4.c, 109P1D4.d oligos) were tested in LNCaP cells in the 3 H-thymidine incorporation assay (measures cellular proliferation). Moreover, the oligonucleotides achieved knockdown of 109P1D4 antigen in cells expressing the protein and had functional effects as described below using the following protocols. Mammalian siRNA transfections: The day before siRNA transfection, the different cell lines were plated in media (RPMI 1640 with 10% FBS w/o antibiotics) at 2x10 3 cells/well in 80 p (96 well plate format) for the proliferation assay. In parallel with the 109P1 D4 specific siRNA oligo, the following sequences were included in every experiment as controls: a) Mock transfected cells with Lipofectamine 2000 (Invitrogen, Carlsbad, CA) and annealing buffer (no siRNA); b) Luciferase-4 specific siRNA (targeted sequence: 5'-AAGGGACGAAGACGAACACUUCTT-3') (SEQ ID NO: 60); and, c) Eg5 specific siRNA (targeted sequence: 5'-AACTGAAGACCTGAAGACAATAA-3') (SEQ ID NO: 61). SiRNAs were used at 10nM and pg/mi Lipofectamine 2000 final concentration. The procedure was as follows: The siRNAs were first diluted in OPTIMEM (serum-free transfection media, Invitrogen) at 0.1 pM (10-fold concentrated) and incubated 5-10 min RT. Lipofectamine 2000 was diluted at 10 pg/ml (10 fold concentrated) for the total number transfections and incubated 5-10 minutes at room temperature (RT). Appropriate amounts of diluted 10-fold concentrated Lipofectamine 2000 were mixed 1:1 with diluted 10-fold concentrated siRNA and incubated at RT for 20-30" (5-fold concentrated transfection solution). 20 pls of the 5-fold concentrated transfection solutions were added to the respective samples and incubated at 37oC for 96 hours before analysis. 3H-Thymidine incorporation assay: The proliferation assay is a 3 H-thymidine incorporation method for determining the proliferation of viable cells by uptake and incorporation of label into DNA. The procedure was as follows: Cells growing in log phase are trypsinized, washed, counted and plated in 96-well WO 2004/098515 PCT/US2004/013568 122 plates at 1000-4000 cells/well in 10% FBS. After 4-8 hrs, the media is replaced. The cells are incubated for 24-72 hrs, pulsed with 3 H-Thy at 1.5 pCi/mI for 14 hrs, harvested onto a filtermat and counted in scintillation cocktail on a Microbeta trilux or other counter. In order to address the function of 109P1 D4 in cells, 109P1 D4 was silenced by transfecting the endogenously expressing 109P1D4 cell line (LNCaP) with the 109P1D4 specific siRNAs (109P1D4.a, 109P1D4.c, and 109P1D4.d) along with negative siRNA controls (Luc4, targeted sequence not represented in the human genome), a positive siRNA control (targeting Eg5) and no siRNA oligo (LF2K) (Figure 23). The results indicated that when these cells are treated with siRNA specifically targeting the 109P1D4 mRNA, the resulting "109P1D4 deficient cells" showed diminished cell proliferation as measured by this assay (e.g., see oligo 109P1D4.a treated cells). These data indicate that 109P1 D4 plays an important role in the proliferation of cancer cells and that the lack of 109P1 D4 clearly decreases the survival potential of these cells. It is to be noted that 109P1 D4 is constitutively expressed in many tumor cell lines. 109P1 D4 serves a role in malignancy; its expression is a primary indicator of disease, where such disease is often characterized by high rates of uncontrolled cell proliferation and diminished apoptosis. Correlating cellular phenotype with gene knockdown following RNAi treatments is important, and allows one to draw valid conclusions and rule out toxicity or other non-specific effects of these reagents. To this end, assays to measure the levels of expression of both protein and mRNA for the target after RNAi treatments are important, including Western blotting, FACS staining with antibody, immunoprecipitation, Northern blotting or RT-PCR (Taqman or standard methods). Any phenotypic effect of the siRNAs in these assays should be correlated with the protein and/or mRNA knockdown levels in the same cell lines. 109P1D4 protein is reduced after treatment with siRNA oligos described above (e.g., 109P1D4.a, etc.) A method to analyze 109P1 D4 related cell proliferation is the measurement of DNA synthesis as a marker for proliferation. Labeled DNA precursors (i.e. 3 H-Thymidine) are used and their incorporation to DNA is quantified. Incorporation of the labeled precursor into DNA is directly proportional to the amount of cell division occurring in the culture. Another method used to measure cell proliferation is performing clonogenic assays. In these assays, a defined number of cells are plated onto the appropriate matrix and the number of colonies formed after a period of growth following siRNA treatment is counted. In 109P1 D4 cancer target validation, complementing the cell survival/proliferation analysis with apoptosis and cell cycle profiling studies are considered. The biochemical hallmark of the apoptotic process is genomic DNA fragmentation, an irreversible event that commits the cell to die. A method to observe fragmented DNA in cells is the immunological detection of histone-complexed DNA fragments by an immunoassay (i.e. cell death detection ELISA) which measures the enrichment of histone-complexed DNA fragments (mono- and oligo-nucleosomes) in the cytoplasm of apoptotic cells. This assay does not require pre-labeling of the cells and can detect DNA degradation in cells that do not proliferate in vitro (i.e. freshly isolated tumor cells). The most important effector molecules for triggering apoptotic cell death are caspases. Caspases are proteases that when activated cleave numerous substrates at the carboxy-terminal site of an aspartate residue mediating very early stages of apoptosis upon activation. All caspases are synthesized as pro-enzymes and activation involves cleavage at aspartate residues. In particular, caspase 3 seems to play a central role in the initiation of cellular events of apoptosis. Assays for determination of caspase 3 activation detect early events of apoptosis. Following RNAi treatments, Western blot detection of active caspase 3 presence or proteolytic cleavage of products (i.e. PARP) found in apoptotic cells further support an active induction of apoptosis. Because the cellular mechanisms that result in apoptosis are complex, each has its advantages and limitations. Consideration of other criteria/endpoints such as cellular morphology, chromatin condensation, membrane blebbing, apoptotic bodies help to further support cell death as apoptotic. Since not all the gene targets that WO 2004/098515 PCT/US2004/013568 123 regulate cell growth are anti-apoptotic, the DNA content of permeabilized cells is measured to obtain the profile of DNA content or cell cycle profile. Nuclei of apoptotic cells contain less DNA due to the leaking out to the cytoplasm (sub-G1 population). In addition, the use of DNA stains (i.e., propidium iodide) also differentiate between the different phases of the cell cycle in the cell population due to the presence of different quantities of DNA in GO/G1, S and G2/M. In these studies the subpopulations can be quantified. For the 1 09P1 D4 gene, RNAi studies facilitate the understanding of the contribution of the gene product in cancer pathways. Such active RNAi molecules have use in identifying assays to screen for mAbs that are active anti-tumor therapeutics. Further, siRNA are administered as therapeutics to cancer patients for reducing the malignant growth of several cancer types, including those listed in Table 1. When 109P1D4 plays a role in cell survival, cell proliferation, tumorigenesis, or apoptosis, it is used as a target for diagnostic, prognostic, preventative and/or therapeutic purposes. Throughout this application, various website data content, publications, patent applications and patents are referenced. (Websites are referenced by their Uniform Resource Locator, or URL, addresses on the World Wide Web.) The present invention is not to be limited in scope by the embodiments disclosed herein, which are intended as single illustrations of individual aspects of the invention, and any that are functionally equivalent are within the scope of the invention. Various modifications to the models and methods of the invention, in addition to those described herein, will become apparent to those skilled in the art from the foregoing description and teachings, and are similarly intended to fall within the scope of the invention. Such modifications or other embodiments can be practiced without departing from the true scope and spirit of the invention.

WO 2004/098515 PCT/US2004/013568 124 TABLES: TABLE I: Tissues that Express 109P1 D4 when malignant: Prostate Bladder Kidney Colon Lymphoma Lung Pancreas Ovary Breast Uterus Stomach Rectum Cervix Lymph Node Bone TABLE Ii: Amino Acid Abbreviations SINGLE LETTER THREE LETTER FULL NAME F Phe phenylalanine L Leu leucine S Ser serine Y Tyr tyrosine C Cys cysteine W Trp tryptophan P Pro proline H His histidine Q Gin glutamine R Arg arginine lie isoleucine M Met methionine T Thr threonine N Asn asparagine K Lys lysine V Val valine A Ala alanine D Asp aspartic acid E Glu glutamic acid G Gly glycine WO 2004/098515 PCT/US2004/013568 125 TABLE III: Amino Acid Substitution Matrix Adapted from the GCG Software 9.0 BLOSUM62 amino acid substitution matrix (block substitution matrix). The higher the value, the more likely a substitution is found in related, natural proteins. (See world wide web URL ikp.unibe.ch/manual/blosum62.html) A C D E F G H I K L M N P Q R S T V W Y 4 0 -2 -1 -2 0 -2 -1 -1 -1 -1 -2 -1 -1 -1 1 0 0 -3 -2 A 9 -3 -4 -2 -3 -3 -1 -3 -1 -1 -3 -3 -3 -3 -1 -1 -1 -2 -2 C 6 2 -3 -1 -1 -3 -1 -4 -3 1 -1 0 -2 0 -1 -3 -4 -3 D 5 -3 -2 0 -3 1 -3 -2 0 -1 2 0 0 -1 -2 -3 -2 E 6 -3 -1 0 -3 0 0 -3 -4 -3 -3 -2 -2 -1 1 3 F 6 -2 -4 -2 -4 -3 0 -2 -2 -2 0 -2 -3 -2 -3 G 8 -3 -1 -3 -2 1 -2 0 0 -1 -2 -3 -2 2 H 4 -3 2 1 -3 -3 -3 -3 -2 -1 3 -3 -1 I 5 -2 -1 0 -1 1 2 0 -1 -2 -3 -2 K 4 2 -3 -3 -2 -2 -2 -1 1 -2 -1 L 5 -2 -2 0 -1-1-1 1-1-1M 6 -2 0 0 1 0 -3 -4 -2 N 7 -1 -2 -1 -1 -2 -4 -3 P 5 1 0 -1 -2 -2 -1 Q 5 -1 -1 -3 -3 -2 R 4 1 -2 -3 -2 S 5 0 -2 -2 T 4 -3 -1 V 11 2 W 7 Y WO 2004/098515 PCT/US2004/013568 126 TABLE IV: HLA Class ill Motifs/Supermotifs TABLE IV (A): HLA Class I Supermotifs/Motifs SUPERMOTIF POSITION POSITION POSITION 2 (Primary Anchor) 3 (Primary Anchor) C Terminus (Primary Anchor) Al TIL VMS FWY A2 LIVMATQ IVMATL A3 VSMATLI RK A24 YFWIVLMT FIYWLM B7 P VILFMWYA B27 RHK FYLWM1VA B44 ED FWYLIMVA B58 ATS FWYLIVMA B62 QLIVMP FWYMVLA MOTIFS Al TSM Y Al DEAS Y A2.1 LMVQIAT VLIMAT A3 LMVISATFCGD KYRHFA Al1 VTMLISAGNCDF KRYH A24 YFWM FLIW A*3101 MVTALIS RK A*3301 MVALFIST RK A*6801 AVTMSL1 RK B*0702 P LMFWYAIV B*3501 P LMFWYIVA B51 P LIVFWYAM B*5301 P IMFWYALV B*5401 P ATIVLMFWY Bolded residues are preferred, italicized residues are less preferred: A peptide is considered motif-bearing if it has primary anchors at each primary anchor position for a motif or supermotif as specified in the above table. TABLE IV (B): HLA Class I Supermotif 1 6 9 W, F, Y, V,.I, L A, V, 1, L, P, C, S, T A, V, I, L, C, S, T, M, Y WO 2004/098515 PCT/US2004/013568 127 TABLE IV (C): HLA Class 11 Motifs MOTIFS 1* anchor 1 2 3 4 5 1* anchor 6 7 8 9 DR4 preferred FMYLIVW M T I VSTCPALIM MH MH deleterious W R WDE DRI preferred MFL/VWY PAMQ VMATSPLIC M AVM deleterious C CH FD CWD GDE D DR7 preferred MFLIVWY M W A IVMSACTPL M IV deleterious C G GRD N G DR3 MOTIFS I anchor 1 2 3 1* anchor 4 5 1* anchor 6 Motif a preferred LIVMFY D Motif b preferred LIVMFAY DNQEST KRH DR Supermotif MFLIVWY VMSTACPLI Italicized residues indicate less preferred or "tolerated" residues TABLE IV (D): HLA Class I Supermotifs POSITION: 1 2 3 4 5 6 7 8 C-terminus

SUPER

MOTIFS Al 1* Anchor 1* Anchor TILtVMS FWY A2 10 Anchor 1* Anchor LIVMATQ LIVMAT, A3 Preferred I Anchor YFW YFW YFW P 10 Anchor VSMATLI (4/5) (3/5) (4/5) (4/5) RK deleterious DE (3/5); DE P (5/5) (415) A24 10 Anchor 1* Anchor Y FWIVLMT FlYWLM B7 Preferred FWY (5/5) 1* Anchor FWY FWY 1*Anchor LIVM (3/5) P (4/5) (3/5) VILFMWYA deleterious DE (3/5); DE G QN DE P(5/5); (3/5) (4/5) (415) (4/5) G(4/5); A(315); QN(315) B27 1* Anchor I*Anchor RHK FYLWMVA B44 1* Anchor 10 Anchor ED FWYLIMVA B58 10 Anchor 1* Anchor ATS FWYLIVMA B62 1* Anchor 1* Anchor QLIVMP FWYM/VLA Italicized residues indicate less preferred or "tolerated" residues WO 2004/098515 PCT/US2004/013568 128 TABLE IV (E): HLA Class I Motifs POSITION 1 2 3 4 5 6 7 8 9 C terminus or C-terminus Al preferred GFYW 1* 0 Anchor DEA YFW P DEQN YFW 1 Anchor 9-mer STM Y deleterious DE RHKLIVMP A G A Al preferred GRHK ASTCLIVM 1*Anchor GSTC ASTC LIVM DE lAnchor 9-mer DEAS Y deleterious A RHKDEPYFW DE PQN RHK PG GP Al preferred YFW I*Anchor DEAQN A YFWQN PASTC GDE P 1*Anchor 10- STM y mer deleterious GP RHKGLIVM DE RHK QNA RHKYFW RHK A Al preferred YFW STCLIVM I *Anchor A YFW PG G YFW 1*Anchor 10- DEAS Y mer deleterious RHK RHKDEPYFW P G PRHK QN A2.1 preferred YFW I*Anchor YFW STC YFW A P 1*Anchor 9-mer LMIVQAT VLIMAT deleterious DEP DERKH RKH DERKH POSITION:1 2 3 4 5 6 7 8 9 C Terminus A2.1 preferred AYFW 1"Anchor LVIM G G FYWL lAnchor 10- LMIVQAT ViM VLIMAT mer deleterious DEP DE RKHA P RKH DERKHRKH A3 preferred RHK 1*Anchor YFW PRHKYF A YFW P 1*Anchor LMVISATFCGD W KYRHFA deleterious DEP DE All preferred A 1*Anchor YFW YFW A YFW YFW P l*Anchor VTLMISAGNCD KRYH F deleterious DEP A G A24 preferred YFWRHK 1*Anchor STC YFW YFW I*Anchor 9-mer YFWM FLIW deleterious DEG DE G QNP DERHKG AQN A24 Preferred 1 *Anchor P YFWP P 1*Anchor 10- YFWM FLIW mer Deleterious GDE QN RHK DE A QN DEA A3101Preferred RHK 1*Anchor YFW P YFW YFW AP 1"Anchor MVTALIS RK Deleterious DEP DE ADE DE DE DE A3301 Preferred 1*Anchor YFW AYFW I*Anchor MVALFIST RK Deleterious GP DE A6801 Preferred YFWSTC I*Anchor YFWLIV YFW P 1*Anchor AVTMSLI M RK deleterious GP DEG RHK A B0702Preferred RHKFWY 1*Anchor RHK RHK RHK RHK PA 1 *Anchor P LMFWYAI V deleterious DEQNP DEP IDE DE GDE QN DE WO 2004/098515 PCT/US2004/013568 129 POSITION1 2 3 4 5 6 7 8 9 C terminus or C-terminus Al preferred GFYW I *Anchor IDEA YFW P DEQN YFW 1*Anchor 9-mer STM y deleterious DE RHKLIVMP A G A Al preferred GRHK ASTCLIVM 1* 0 Anchor GSTC ASTC LIVM DE 1*Anchor 9-mer DEAS y deleterious A RHKDEPYFW DE PQN RHK PG GP B3501 Preferred FWYLIVM 1*Anchor FWY FWY I*Anchor P LMFWY/V A deleterious AGP G G B51 Preferred LIVMFWY 1"Anchor FWY STC FWY G FWY 1 *Anchor P LIVFWYA M deleterious AGPDER DE G DEQN GDE HKSTC B5301 preferred LIVMFWY 1*Anchor FWY STC FWY LIVMFWYFWY I*Anchor P IMFWYAL V deleterious AGPQN G RHKQN DE B5401 preferred FWY 1*Anchor FWYLIVM LIVM ALIVM FWYA 1 0 Anchor P P ATIVLMF WY deleterious GPQNDE GDESTC RHKDE DE QNDGE DE WO 2004/098515 PCT/US2004/013568 130 TABLE IV (F): Summary of HLA-supertypes Overall phenotypic frequencies of HLA-supertypes in different ethnic populations Specificity Phenotypic frequency ____ Supertype Posiion 2 C-Terminus Caucasian N.A. Black Japanese Chinese Hispanic average B7 P AILMVFWY43.2 55.1 57.1 43.0 49.3 49.5 A3 AILMVST RK 37.5 42.1 5.8 52.7 43.1 44.2 n2 AILMVT AILMVT 45.8 39.0 2.4 45.9 43.0 42.2 A24 YF (WIVLMT)FI (YWLM) 23.9 |38.9 8.6 40.1 38.3 40.0 B44 E (D) |FWYLIMVA 43.0 21.2 2.9 39.1 39.0 37.0 al TI (LVMS) |FWY 47.1 16.1 21.8 14.7 26.3 25.2 B27 RHK FYL (WMI) 28.4 26.1 13.3 13.9 35.3 23.4 B62 QL (IVMP) |FWY (MIV)12.6 4.8 36.5 25.4 11.1 18.1 B58 ATS FWY (LIV) 10.0 25.1 1.6 9.0 5.9 10.3 TABLE IV (G): Calculated population coverage afforded by different HLA-supertype combinations HLA-supertypes Phenotypic frequency Caucasian N.A Blacks |Japanese Chinese Hispanic Average 83.0 86.1 87.5 88.4 86.3 86.2 2, A3 and B7 99.5 98.1 100.0 99.5 99.4 99.3 A2, A3, B7, A24, B44 99.9 99.6 100.0 99.8 99.9 99.8 and Al A2, A3, B7, A24, B44, Al, B27, B62, and B 58 Motifs indicate the residues defining supertype specificites. The motifs incorporate residues determined on the basis of published data to be recognized by multiple alleles within the supertype. Residues within brackets are additional residues also predicted to be tolerated by multiple alleles within the supertype. Table V: Frequently Occurring Motifs Name avrg. i Description Potential Function identity ___________ _________________ Nucleic acid-binding protein functions as transcription factor, nuclear location zf-C2H2 34% inc finger, C2H2 type probable Cytochrome b(N- membrane bound oxidase, generate cytochrome b N 68% terminal)/b6lpetB superoxide domains are one hundred amino acids long and include a conserved Ig 19% Immunoglobulin domain intradomain disulfide bond. tandem repeats of about 40 residues, each containing a Trp-Asp motif. Function in signal transduction and WD40 18% WD domain, G-beta repeat protein interaction may function in targeting signaling PDZ 23% PDZ domain molecules to sub-membranous sites LRR 28% Leucine Rich Repeat short sequence motifs involved in protein-protein interactions conserved catalytic core common to both serine/threonine and tyrosine protein kinases containing an ATP Pkinase 23% Protein kinase domain binding site and a catalytic site WO 2004/098515 PCT/US2004/013568 131 pleckstrin homology involved in intracellular signaling or as constituents PH 16% PH domain of the cytoskeleton 30-40 amino-acid long found in the extracellular domain of membrane EGF 34% EGF-like domain bound proteins or in secreted proteins Reverse transcriptase (RNA-dependent DNA Rvt 9% polymerase) Cytoplasmic protein, associates integral Ank 25% Ank repeat membrane proteins to the cytoskeleton NADH- membrane associated. Involved in Ubiquinone/plastoquinone proton translocation across the Oxidored ql 32% (complex 1), various chains membrane calcium-binding domain, consists of a12 residue loop flanked on both sides by a Efhand 24% EF hand 12 residue alpha-helical domain Retroviral aspartyl Aspartyl or acid proteases, centered on Rvp 79% protease a catalytic aspartyl residue extracellular structural proteins involved in formation of connective tissue. The Collagen triple helix repeat sequence consists of the G-X-Y and the Collagen 42% (20 copies) polypeptide chains forms a triple helix. Located in the extracellular ligand binding region of receptors and is about 200 amino acid residues long with two pairs of cysteines involved in disulfide Fn3 20% Fibronectin type Ill domain bonds seven hydrophobic transmembrane regions, with the N-terminus located 7 transmembrane receptor extracellularly while the C-terminus is 7tm_1 19% (rhodopsin family) cytoplasmic. Signal through G proteins Table VI: Post-translational modifications of 109P1D4 0-qlycosylation sites 231 S 238 S 240 T 266 T 346 T 467 T 551 T 552 S 555 T 595 T 652 S 654 S 660 T 790 T 795 T 798 T 804 S 808 S 923 T 927 T 954 T 979 S 982 S 983 S WO 2004/098515 PCT/US2004/013568 132 985 S 986 S 990 S 999 T 1000 T 1006 S 1017 S 1020 T Serine phosphorylation sites 50 DLNLSLIPN (SEQ ID NO: 62) 147 VINISIPEN (SEQ ID NO: 63) 152 IPENSAINS (SEQ ID NO: 64) 238 ILQVSVTDT (SEQ ID NO: 65) 257 EIEVSIPEN (SEQ ID NO: 66) 428 LDYESTKEY (SEQ ID NO: 67) 480 PENNSPGIQ (SEQ ID NO: 68) 489 LTKVSAMDA (SEQ ID NO: 69) 495 MDADSGPNA (SEQ ID NO: 70) 559 TVFVSIIDQ (SEQ ID NO: 71) 567 QNDNSPVFT (SEQ ID NO: 72) 608 AVTLSILDE (SEQ ID NO: 73) 630 RPNISFDRE (SEQ ID NO: 74) 638 EKQESYTFY (SEQ ID NO: 75) 652 GGRVSRSSS (SEQ ID NO: 76) 654 RVSRSSSAK (SEQ ID NO: 77) 655 VSRSSSAKV (SEQ ID NO: 78) 656 SRSSSAKVT (SEQ ID NO: 79) 714 EVRYSIVGG (SEQ ID NO: 80) 789 LVRKSTEAP (SEQ ID NO: 81) 805 ADVSSPTSD (SEQ ID NO: 82) 808 SSPTSDYVK (SEQ ID NO: 83) 852 NKQNSEWAT (SEQ ID NO: 84) 877 KKKHSPKNL (SEQ ID NO: 85) 898 DDVDSDGNR (SEQ ID NO: 86) 932 FKPDSPDLA (SEQ ID NO: 87) 941 RHYKSASPQ (SEQ ID NO: 88) 943 YKSASPQPA (SEQ ID NO: 89) 982 ISKCSSSSS (SEQ ID NO: 90) 983 SKCSSSSSD (SEQ ID NO: 91) 984 KCSSSSSDP (SEQ ID NO: 92) 985 CSSSSSDPY (SEQ ID NO: 93) 990 SDPYSVSDC (SEQ ID NO: 94) 1006 EVPVSVHTR (SEQ ID NO: 95) Threonine phosphorylation sites 29 EKNYTIREE (SEQ ID NO: 96) 81 IEEDTGEIF (SEQ ID NO: 97) 192 DVIETPEGD (SEQ ID NO: 98) 252 VFKETEIEV (SEQ ID NO: 99) 310 TGLITIKEP (SEQ ID NO: 100) 320 DREETPNHK (SEQ ID NO: 101) 551 VPPLTSNVT (SEQ ID NO: 102) 790 VRKSTEAPV (SEQ ID NO: 103) 856 SEWATPNPE (SEQ ID NO: 104) 924 NWVTTPTTF (SEQ ID NO: 105) 927 TTPTTFKPD (SEQ ID NO: 106) 999 GYPVTTFEV (SEQ ID NO: 107) 1000 YPVTTFEVP (SEQ ID NO: 108) Tyrosine phosphorvlation sites 67 FKLVYKTGD (SEQ ID NO: 109) WO 2004/098515 PCT/US2004/013568 133 158 INSKYTLPA (SEQ ID NO: 110) 215 EKDTYVMKV (SEQ ID NO: 111) 359 IDIRYIVNP (SEQ ID NO: 112) 423 ETAAYLDYE (SEQ ID NO: 113) 426 AYLDYESTK (SEQ ID NO: 114) 432 STKEYAIKL (SEQ ID NO: 115) 536 KEDKYLFTI (SEQ ID NO: 116) 599 TDPDYGDNS (SEQ ID NO: 117) 642 SYTFYVKAE (SEQ ID NO: 118) 682 SNCSYELVL (SEQ ID NO: 119) 713 AEVRYSIVG (SEQ ID NO: 120) 810 PTSDYVKIL (SEQ ID NO: 121) 919 TMGKYNWVT (SEQ ID NO: 122) 989 SSDPYSVSD (SEQ ID NO: 123) 996 SDCGYPVTT (SEQ ID NO: 124) Table VII: Search Peptides 109P1D4 v.1 - 9-mers, 10-mers and 15-mers (SEQ ID NO: 125) MDLLSGTYIF AVLLACVVFH. SGAQEKNYTI REEMPENVLI GDLLKDLNLS LIPNKSLTTA 60 MQFKLVYKTG DVPLIRIEED TGEIFTTGAR IDREKLCAGI PRDEHCFYEV EVAILPDEIF 120 RLVKIRFLIE DINDNAPLFP ATVINISIPE NSAINSKYTL PAAVDPDVGI NGVQNYELIK 180 SQNIFGLDVI ETPEGDKMPQ LIVQKELDRE EKDTYVMKVK VEDGGFPQRS STAILQVSVT 240 DTNDNHPVFK ETEIEVSIPE NAPVGTSVTQ LHATDADIGE NAKIHFSFSN LVSNIARRLF 300 HLNATTGLIT IKEPLDREET PNHKLLVLAS DGGLMFARAM VLVNVTDVND NVPSIDIRYI 360 VNPVNDTVVL SENIPLNTKI ALTTVTDKDA DHNGRVTCFT DHEIPFRLRP VFSNQFLLET 420 AAYLDYESTK EYAIKLLAAD AGKPPLNQSA MLFIKVKDEN DNAPVFTQSF VTVSIPENNS 480 PGIQLTKVSA MDADSGPNAK INYLLGPDAP PEFSLDCRTG MLTVVKKLDR EKEDKYLFTI 540 LAKDNGVPPL TSNVTVFVSI IDQNDNSPVF THNEYNFYVP ENLPRHGTVG LITVTDPDYG 600 DNSAVTLSIL DENDDFTIDS QTGVIRPNIS FDREKQESYT FYVKAEDGGR VSRSSSAKVT 660 INVVDVNDNK PVFIVPPSNC SYELVLPSTN PGTVVFQVIA VDNDTGMNAE VRYSIVGGNT 720 RDLFAIDQET GNITLMEKCD VTDLGLHRVL VKANDLGQPD SLFSVVIVNL FVNESVTNAT 780 LINELVRKST EAPVTPNTEI ADVSSPTSDY VKILVAAVAG TITVVVVIFI TAVVRCRQAP 840 HLKAAQKNKQ NSEWATPNPE NRQMIMMKKK KKKKKHSPKN LLLNFVTIEE TKADDVDSDG 900 NRVTLDLPID LEEQTMGKYN WVTTPTTFKP DSPDLARHYK SASPQPAFQI QPETPLNSKH 960 HTIQELPLDN TFVACDSISK CSSSSSDPYS VSDCGYPVTT FEVPVSVHTR PVGIQVSNTT 1020 F 1021 109P1D4 v.2 (both ends diff from v.1) N' terminal 9-mers aa -30 to 8 MRTERQWVLIQIFQVLCGLIQQTVTSVPGMDLLSGTY (SEQ ID NO: 126) 1 0-mers aa -30 to 9 MRTERQWVLIQIFQVLCGLIQQTVTSVPGMDLLSGTYI (SEQ ID NO: 127) 15-mers aa -30 to 14 MRTERQWVLIQIFQVLCGLIQQTVTSVPGMDLLSGTYIFAVLL (SEQ ID NO: 128) 109P1D4 v.2 C' Terminal 9 mers: aa 1004 to 1025 PVSVHTRPTDSRTSTIEICSEI (SEQ ID NO: 129) 10 mers: aa 1003 to 1025 VPVSVHTRPTDSRTSTIEICSEI (SEQ ID NO: 130) 15 mers: aa 997 to 1025 VTTFEVPVSVHTRPTDSRTSTIEICSEI (SEQ ID NO: 131) 109P1D4 v.3 9 mers: aa 1004 to 1347 (SEQ ID NO: 132) PVSVHTRPPMKEVVRSCTPMKESTTMEIWIHPQPQRKSEGKVAGKSQRRVTFHLPEGSQESSSDG GLGDHDAGSLTSTSHGLPLGYPQEEYFDRATPSNRTEGDGNSDPESTFI PGLKKAAEITVQPTVE EASDNCTQECLIYGHSDACWMPASLDHSSSSQAQASALCHSPPLSQASTQHHSPRVTQTIALCHS

PPVTQTIALCHSPPPIQVSALHHSPPLVQATALHHSPPSAQASALCYSPPLAQAAAISHSSPLPQ

WO 2004/098515 PCT/US2004/013568 134 VIALHRSQAQSSVSLQQGWVQGADGLCSVDQGVQGSATSQFYTMSERLHPS DDSIKVIPLTTFTP RQQARPSRGDS PMEEHPL 10 mers: aa 1003 to 1347 (SEQ ID NO: 133) VPVSVHTRPPMKEVVRSCTPMKESTTMEIWIHPQPQRKSEGKVAGKSQRRVTFHLPEGSQESSSD GGLGDHDAGSLTSTSHGLPLGYPQEEYFDRATPSNRTEGDGNSDPESTFI PGLKKAAEITVQPTV EEASDNCTQECLIYGHSDACWMPASLDHSSSSQAQASALCHSPPLSQASTQHHS PRVTQTIALCH SPPVTQTIALCHSPPPIQVSALHHSPPLVQATALHHS PPSAQASALCYSPPLAQAAATSHS SPLP QVIALHRSQAQS SVSLQQGWVQGADGLCSVDQGVQGSATSQFYTMSERLHPSDDSIKVI PLTTFT PRQQARPSRGDSPMEEHPL 15 mers: aa 998 to 1347 (SEQ ID NO: 134) VTTFEVPVSV HTRPPMKEVV RSCTPMKEST TMEIWIHPQP QRKSEGKVAG KSQRRVTFHL PEGSQESSSD GGLGDHDAGS LTSTSHGLPL GYPQEEYFDR ATPSNRTEGD GNSDPESTFI PGLKKAAEIT VQPTVEEASD NCTQECLIYG HSDACWMPAS LDHSSSSQAQ ASALCHSFL SQASTQHHSP RVTQTIALCH SPPVTQTIAL CHSPPPIQVS ALHHSPPLVQ ATALHSPPS AQASALCYSP PLAQAAAISH SSPLPQVIAL HRSQAQSSVS LQQGWVQGAD GLCSVDQGVQ GSATSQFYTM SERLHPSDDS IKVIPLTTFT PRQQARPSRG DSPMEEHPL 109P1D4 v.4 (deleting 10 aa, 1039-1048, from v.1) 9-mers aa 1031-1056 (deleting 10 aa, 1039-1048, from v.1) IWIHPQPQSQRRVTFH (SEQ ID NO: 135) 10-mers aa 1030- 1057 (deleting 10 aa, 1039-1048, from v.1) EIWIHPQPQSQRRVTFHL (SEQ ID NO: 136) 15-mers aa 1025- 1062 (deleting 10 aa, 1039-1048, from v.1) ESTTMEIWIHPQPQSQRRVTFHLPEGSQ (SEQ ID NO: 137) 109P1D4 v.5 (deleting 37 aa, 1012-1048, from v.1) 9-mers aa 1004-1056 (deleting 37 aa, 1012-1048, from v.1) PVSVHTRPSQRRVTFH (SEQ ID NO: 138) 10-mers aa 1003-1057 (deleting 37 aa, 1012-1048, from v.1) VPVSVHTRPSQRRVTFHL (SEQ ID NO: 139) 15-mers aa 998-1062 (deleting 37 aa, 1012-1048, from v.1) VTTFEVPVSVHTRPSQRRVTFHLPEGSQ (SEQ ID NO: 140) 109P1D4 v.6 (both ends diff from v.1) N' terminal 9-mers: aa -23 to 10 (excluding I and 2) MTVGFNSDISSVVRVNTTNCHKCLLSGTYIF (SEQ ID NO: 141) 1 0-mers: aa -23 to 11 (excluding I and 2) MTVGFNSDISSVVRVNTTNCHKCLLSGTYIFA (SEQ ID NO: 142) 15-mers: aa -23 to 17 (excluding 1 and 2) MTVGFNSDISSVVRVNTTNCHKCLLSGTYIFAVLLVC (SEQ ID NO: 143) 109P1D4 v.6 C' terminal 9-mers: aa 1004-1016 PVSVHTRPTDSRT (SEQ ID NO: 144) 10-mers: aa 1003-1016 VPVSVHTRPTDSRT (SEQ ID NO: 145) 15-mers: aa 998-1016 VTTFEVPVSVHTRPIDSRT (SEQ ID NO: 146) 109P1 D4 v.7 (N-terminal 21 aa diff from those in v.6) WO 2004/098515 PCT/US2004/013568 135 N' terminal 9-mers aa -21 to 10 (excluding I and 2) MFRVGFLIISSSSSLSPLLLVSVVRVNTT (SEQ ID NO: 147) 1 0-mers aa -21 to 11 (excluding 1 and 2) MFRVGFLIISSSSSLSPLLLVSVVRVNTTN (SEQ ID NO: 148) 15-mers aa -21 to 16 (excluding I and 2) MFRVGFLIISSSSSLSPLLLVSVVRVNTTNCHKCL (SEQ ID NO: 149) 109P1D4 v.8 9-mers aa 1099-1126 (excluding 1117 and II18) TFIPGLKKEITVQPTV (SEQ ID NO: 150) 10-mers aa1098-1127 (excluding 1117 and 1118) STFIPGLKKEITVQPTVE (SEQ ID NO: 151) 15-mers aa 1093-1131 (excluding 1117 and 1118) NSDPESTFIPGLKKEITVQPTVEEASDN (SEQ ID NO: 152) 109P1D4 v.1, v.2 and v.3 SNP variants Al 5V 9-mers TYIFAVLLVCVVFHSGA (SEQ ID NO: 153) 1 0-mers GTYIFAVLLVCVVFHSGAQ (SEQ ID NO: 154) 15-mers MDLLSGTYIFAVLLVCVVFHSGAQEKNYT (SEQ ID NO: 155) 109P1D4 v.1, v.2 and v.3 SNP variants M341 9-mers KNYTIREEIPENVLIGD (SEQ ID NO: 156) 10-mers EKNYTIREEIPENVLIGDL (SEQ ID NO: 157) 15-mers HSGAQEKNYTIREEIPENVLIGDLLKDLN (SEQ ID NO: 158) 109P1D4 v.1, v.2 and v.3 SNP variants M341 and D42N 9-mers KNYTIREEIPENVLIGN (SEQ ID NO: 159) 1O-mers EKNYTIREEIPENVLIGNL (SEQ ID NO: 160) 15-mers HSGAQEKNYTIREEIPENVLIGNLLKDLN (SEQ ID NO: 161) 109P1D4 v.1, v.2 and v.3 SNP variants D42N 9-mers MPENVLIGNLLKDLNLS (SEQ ID NO: 162) 10-mers EMPENVLIGNLLKDLNLSL (SEQ ID NO: 163) 15-mers YTIREEMPENVLIGNLLKDLNLSLIPNKS (SEQ ID NO: 164) 109P1D4 v.1, v.2 and v.3 SNP variants D42N and M341 9-mers IPENVLIGNLLKDLNLS (SEQ ID NO: 165) 10-mers EIPENVLIGNLLKDLNLSL (SEQ ID NO: 166) WO 2004/098515 PCT/US2004/013568 136 15-mers YTIREEIPENVLIGNLLKDLNLSLIPNKS (SEQ ID NO: 167) 109P1D4 v.1, v.2 and v.3 SNP variants A60T 9-mers IPNKSLTTTMQFKLVYK (SEQ ID NO: 168) 10-mers LIPNKSLTTTMQFKLVYKT (SEQ ID NO: 169) 15-mers DLNLSLIPNKSLTTTMQFKLVYKTGDVPLI (SEQ ID NO: 170) 109P1D4 v.1, v.2 and v.3 SNP variants 11 54V 9-mers ISIPENSAVNSKYTLPA (SEQ ID NO: 171) 10-mers NISIPENSAVNSKYTLPAA (SEQ ID NO: 172) 15-mers PATVINISIPENSAVNSKYTLPAAVDPDV (SEQ ID NO: 173) 109P1 D4 v.1, v.2 and v.3 SNP variants V2921 9-mers IHFSFSNLISNIARRLF (SEQ ID NO: 174) 1 0-mers KIHFSFSNLISNIARRLFH (SEQ ID NO: 175) 15-mers IGENAKIHFSESNLISNIARRLFHLNATT (SEQ ID NO: 176) 109P1D4 v.1, v.2 and v.3 SNP variants T420N 9-mers FSNQFLLENAAYLDYES (SEQ ID NO: 177) 10-mers VFSNQFLLENAAYLDYEST (SEQ ID NO: 178) 15-mers FRLRPVFSNQFLLENAAYLDYESTKEYAI (SEQ ID NO: 179) 109P1D4 v.1, v.2 and v.3 SNP variants T486M 9-mers NNSPGIQLMKVSAMDAD (SEQ ID NO: 180) 10-mers ENNSPGIQLMKVSAMDADS (SEQ ID NO: 181) 15-mers TVSIPENNSPGIQLMKVSAMDADSGPNAK (SEQ ID NO: 182) 109P1D4 v.1, v.2 and v.3 SNP variants T486M and M491T 9-mers NNSPGIQLMKVSATDAD (SEQ ID NO: 183) 10-mers ENNSPGIQLMKVSATDADS (SEQ ID NO: 184) 15-mers TVSIPENNSPGIQLMKVSATDADSGPNAK (SEQ ID NO: 185) 109P1D4 v.1, v.2 and v.3 SNP variants T486M and M491T and K500E 15-mers TVSIPENNSPGIQLMKVSATDADSGPNAE (SEQ ID NO: 186) WO 2004/098515 PCT/US2004/013568 137 109P1D4 v.1, v.2 and v.3 SNP variants T486M and K500E 15-mers TVSIPENNSPGIQLMKVSAMDADSGPNAE (SEQ ID NO: 187) 109P1D4 v.1, v.2 and v.3 SNP variants M491T 9-mers IQLTKVSATDADSGPNA (SEQ ID NO: 188) 10-mers GIQLTKVSATDADSGPNAK (SEQ ID NO: 189) 15-mers ENNSPGIQLTKVSATDADSGPNAKINYLL (SEQ ID NO: 190) 109P1D4 v.1, v.2 and v.3 SNP variants M491T and T486M 9-mers IQLNKVSATDADSGPNA (SEQ ID NO: 191) 10-mers GIQLNKVSATDADSGPNAK (SEQ ID NO: 192) 15-mers ENNSPGIQLNKVSATDADSGPNAKINYLL (SEQ ID NO: 193) 109P1D4 v.1, v.2 and v.3 SNP variants M491T and T486M and K500E 10-mers GIQLNKVSATDADSGPNAE (SEQ ID NO: 194) 15-mers ENNSPGIQLNKVSATDADSGPNAEINYLL (SEQ ID NO: 195) 109P1D4 v.1, v.2 and v.3 SNP variants M491T and K500E 15-mers ENNSPGIQLTKVSATDADSGPNAEINYLL (SEQ ID NO: 196) 109P1D4 v.1, v.2 and v.3 SNP variants K500E 9-mers DADSGPNAEINYLLGPD (SEQ ID NO: 197) 1 0-mers MDADSGPNAEINYLLGPDA (SEQ ID NO: 198) 15-mers TKVSAMDADSGPNAEINYLLGPDAPPEFS (SEQ ID NO: 199) 109P1D4 v.1, v.2 and v.3 SNP variants K500E and M491T 10-mers TDADSGPNAEINYLLGPDA (SEQ ID NO: 200) 15-mers TKVSATDADSGPNAEINYLLGPDAPPEFS (SEQ ID NO: 201) 109P1D4 v.1, v.2 and v.3 SNP variants K500E and M491T and T486M 15-mers MKVSATDADSGPNAEINYLLGPDAPPEFS (SEQ ID NO: 202) 109P1D4 v.1, v.2 and v.3 SNP variants K500E and T486M 15-mers MKVSAMDADSGPNAEINYLLGPDAPPEFS (SEQ ID NO: 203) 109P1D4 v.1, v.2 and v.3 SNP variants WO 2004/098515 PCT/US2004/013568 138 C517R 9-mers APPEFSLDRRTGMLTVV (SEQ ID NO: 204) 10-mers DAPPEFSLDRRTGMLTVVK (SEQ ID NO: 205) 1 5-mers INYLLGPDAPPEFSLDRRTGMLTVVKKLDRE (SEQ ID NO: 206) 109P1D4 v., v.2 and v.3 SNP variants N576K 9-mers PVFTHNEYKFYVPENLP (SEQ ID NO: 207) 10-mers SPVFTHNEYKFYVPENLPR (SEQ ID NO: 208) 15-mers DQNDNSPVFTHNEYKFYVPENLPRHGTVG (SEQ ID NO: 209) 109P1 D4 v.1, v.2 and v.3 SNP variants S678Y 9-mers KPVFIVPPYNCSYELVLPS (SEQ ID NO: 210) 1 0-mers NKPVFIVPPYNCSYELVLPST (SEQ ID NO: 211) 15-mers VDVNDNKPVFIVPPYNCSYELVLPSTNPG (SEQ ID NO: 212) 109P1D4 v.1, v.2 and v.3 SNP variants S678Y and C680Y 9-mers KPVFIVPPYNYSYELVLPS (SEQ ID NO: 213) 10-mers NKPVFIVPPYNYSYELVLPST (SEQ ID NO: 214) 15-mers VDVNDNKPVFIVPPYNYSYELVLPSTNPG (SEQ ID NO: 215) 109P1D4 v.1, v.2 and v.3 SNP variants C680Y 9-mers VFIVPPSNYSYELVLPS (SEQ ID NO: 216) 10-mers PVFIVPPSNYSYELVLPST (SEQ ID NO: 217) 15-mers VNDNKPVFIVPPSNYSYELVLPSTNPGTV (SEQ ID NO: 218) 109P1D4 v.1, v.2 and v.3 SNP variants C680Y and S678Y 9-mers VFIVPPYNYSYELVLPS (SEQ ID NO: 219) 10-mers PVFIVPPYNYSYELVLPST (SEQ ID NO: 220) 15-mers VNDNKPVFTVPPYNYSYELVLPSTNPGTV (SEQ ID NO: 221) 109P1D4 v.1, v.2 and v.3 SNP variants T7901 9-mers INELVRKSIEAPVTPNT (SEQ ID NO: 222) 10-mers LINELVRKSIEAPVTPNTE (SEQ ID NO: 223) 15-mers VTNATLINELVRKSIEAPVTPNTEIADVS (SEQ ID NO: 224) WO 2004/098515 PCT/US2004/013568 139 109PID4 v.1, v.2 and v.3 SNP variants K846M 9-mers HLKAAQKNMQNSEWATP (SEQ ID NO: 225) 10-mers PHLKAAQKNMQNSEWATPN (SEQ ID NO: 226) 15-mers RCRQAPHLKAAQKNMQNSEWATPNPENRQ (SEQ ID NO: 227) 109P1D4 v.1, v.2 and v.3 SNP variants F855V 9-mers SPKNLLLNVVTIEETKA (SEQ ID NO: 228) 10-mers HSPKNLLLNVVTIEETKAD (SEQ ID NO: 229) 15-mers KKKKKHSPKNLLLNVVTIEETKADDVDSD (SEQ ID NO: 230) 109P1D4 v.1, v.2 and v.3 SNP variants S958L 9-mers IQPETPLNLKHHIIQEL (SEQ ID NO: 231) 10-mers QIQPETPLNLKHHIIQELP (SEQ ID NO: 232) 15-mers PQPAFQIQPETPLNLKHHIIQELPLDNTF (SEQ ID NO: 233) 109P1D4 v.1, v.2 and v.3 SNP variants K980N 9-mers FVACDSISNCSSSSSDP (SEQ ID NO: 234) 10-mers TFVACDSISNCSSSSSDPY (SEQ ID NO: 235) 15-mers LPLDNTFVACDSISNCSSSSSDPYSVSDC (SEQ ID NO: 236) WO 2004/098515 PCT/US2004/013568 140 Tables Vill - XXI: Table VII11 - 109P1 D4v.1 - Al - [Table VIII- 109P1D4v.1 -Al-I TbeVi 0PDvl-l Tablee Vlll - 109P1DDv.1l--A1 9-mers -- _m Each peptide is a portion of Each peptide is a portion of Each peptide is a portion of SEQ ID NO: 3; each start SEQ ID NO: 3; each start SEQ ID NO: 3; each start position is specified, position is specified, the position is specified the length of peptide is 9 amino length of peptide is 9 amino length of peptide is 9 amino acids, and the end positon for acids, and the end position for. acids, and the end position for each peptide is the start each peptide is the start each peptide is the start position plus eight position plus eight. p l Start uccrej ubseque ta 9101 DLEEQTMGK '0F. 50 0 !895 DKDSDGNRV 1 0 399 TDHIP 2500 118511FTTGARID ~.2T5 '[700 AVDNDTGMN, 0,5 00 1895 ioIPIGD 1&00 1.250 f3 D N T VIT PGDK1zoo 11192 iIPEGDKMq' 1,25 !F802 oVSSPTSDY7o.soo I ENAKIHF 11.250 85 NPENQMM [Cl A0 55 DADlGENAK IOI(0ITNISIS 1151 70 VDLLR .0 492 DADSGPNAK 10.000 0500 S LNTi 5 I 1q j725 1631 AVDPDYGIN [5000 711Vclk[100 CSl Sj.99p. 131 EIF TOOO 158 TMTW .0 16 DIRL~ .5 242 TNDNHPVFK 8TG5I00 00500 527O.5 10 0.450 9ASDGGLMPA3.0 f78NAVSIf09043 LAAG 040 59 TAMQrKLVY250 _ ____ t8040 73I KCDVTDLGL 2500 012~iDlN~~.0i126VIEAYO30 354_ SIDIVN2.0 ___-190KSRPA 030 l55 NVPSIDIRY 500 5 2 j SPDLARHYK IO 6 q 0.750 j L V F 050 SLEEQTMGKY 225 F T0 11 1 STEAPVTPN 2250, 65 EYFV065 ~ 66 NNPH 020 25 1.8000 8971 DSDGNRVTL 1.500 j9TDPII065 ~DVSDR120 2 NSPGIQLTK 50 ________ ____ 49 SGPNAEKINY__ 0.2 94 1lRE?9I .5 '91 VSDCGYPVT{ .50 800STDY .0 6 KTDVPLiR K1.2502 F0 I Table F 1O9NIqlv.15 I741 VTDLGLHRV[ 1.5 0TILVKLD .SO__A-O-ir 273] ATDADIGEN .120L9: LEDF ~o Each pep t92! iKA d eVDSDG 0 .pr 00 '[ q)[A G _qLM K. 70SEQ I NO:V IV,~q_ 3; each start !Fj_ 9:1, ~ ~ ~ ~ ~ ~ poito isA speifed tIFY_5_6heI . '7- I-LRF-T !FXLlength_ of peptide~ _s 9 ain [ 3~TTARD PL Y 25D1 1 ?77- FATLINLV.2.25 F897IFEDqNTLI1.50 'F_9F _GNPENRQMI Fo51.5DPVPS l F _ PNAIa D 0.25 qyqD L 6 [N\/LIGDLLK? Tr_? GVNYLI [5.. . ...

P.S.. 9-1FY-DCi PVFT q ,[804 ssTOXOKI56- 1316 ,ISFIED NHIC0 90 28 LIEfNDN 00 WO 2004/098515 PCT/US2004/013568 141 Each peptide is a portion of Table IX- 1O9PID4v- TabeIX-109PD4l SEQ ID NO: 3; each start L Al-lO-mers position is specified, the postio isspeifid, heEach peptide is a portion of I Each peptide is a portion of length of peptide is 10 amino Se acids, and the end position forp each peptide is the start position plu peptide is 10 acids, and length of peptide is 10 amino, positioni plus nine. L _Iacids,_and the end position for, acids, and the end position for! OS[ Subssequeince i Score each peptide is the start each peptide is the start 169, LLETaAYLDY 225.000 poiion plus nine, position plus nine. 8 DLEEqYGKY 4.000e Score Pos Subsq 26 DSGPnAKINY 37.500 P_6__s7 P--n - !j17 DIgNAKI 1.00§J3j IKEPIDREET .40 9SF iP PAI1.00 LSNPLNT_2.0190 RTMITWK 1.000 44,1 VNESvTNATL' q.450j1 1416' fiADgGSR 18.000~ 5 ASDGgLMPAR_ 10 _ SIeAVMI 0.300 36VTDPdYGDNS~ 2~o 5 I800D .OO ~ 2i SMFK .0 TIDSqTGVR R 1 1.000 I757 SSDPySVSDC T500 I~9 D~NP~ .0 28 N~MFK .5 L2DNVPsIDIRY 6.250 i Y!-X.10244DDgMEV025 1 FTDHelPFRL 650 'fj- FPTD-npPEFL 0.625 7j5 QSPDIFSWI .30 5~SSPtSDYM(600 .- ~.,-.. .. ___KQESyIFYVK) I 5.00 __2666 TDpDE .5 450 FIVPpSNCSY i0.30 5 I6STF.ApVTPN 4.500 D 0.25 I -n-6 DARIK020 47AV21D NI OD 62 ' 286 SE-rYSIVI 2L 4500 _ - L- 2 880 NNSkglQLTK 2.00 50I ETGNE 2.500, GLP 0.50 PS5 K LGdAPEF 72.5000____ __ 767 SDCrgVT 2.500ej 4 ETiLG. 250 76 LGPPF1 2.000.V( - I WDnDNKP 0 .500I P159I la VVS 0.200 Tl EnNN FIs 6, NPEQMIM 112 ETeVS2gPE 1721 i0.500 ILI 4 0H F,~IEpDT ~13OI64 KAOTvDSDGN 0.500 III2 DAD0gPNAKI 1000 F53 VLNSgLR 1.50 1369F F V I Rni _.D 0, Tal XE aOPDv1 G -LIvDD 1EMK~ .000R j.1GnA.HF--.0 ql115[lf AT~IENA[772500 332o _lITnDSP . 021--m Each peptide is a portion of VTD5nDNHP .250 -SEQ ID NO: 3; each start f~3~NPErQ~MM~ 1.25 110 CD~DLGH 000position is specified, the r~1 TE~VSIE 11.15 661 DD~dNRV{.00Ilength of peptide is9 amino ____ -aacidsaandtthe end position for 1210AADgKPLN 1000AIDeTGNT 000each peptide is the start [264: DAD~~~gPNAKI'~~1.0positio AplusFQ nin.50I.pstopuseh. [ eguA C SS r 0e 4.0 7] -AIJNK][.0 69 T1 IE tlDD I9.00 __________________3 _ --- ------Y 19 .9 0 f1IGDSPVlm EL ENA 1.625 1-1 !FYT qT rD N -P[SErID O: 3;eachsta) fq- l P -ErQ~lM~lj 1e25 K D CL F.9,ps0ini0peiid h GIFO.06 00h fpetd 435VV6nDKP FLET50081 91 4s ACDS]SKCSS t500 WO 2004/098515 PCT/US2004/013568 142 Table X- 109P1 D4v.1 - IfTable X - 1091PI D4v. I- LTable X- 109PI D4v.1 A0201-9-mers __jA0201-9-mers _I -A0201-9-mers _ Each peptide is a portion of Each peptide is a portion of Each peptide is a portion of SEQ ID NO: 3; each start SEQ ID NO: 3; SEQ ID NO: 3; each start position is specified, the position is specified, the position is specified, the length of peptide is 9 amino length of peptide is 9 amino length of peptide is 9 amino acids, and the end position fori acids, and the end position for: acids and the end position for each peptide is the start each peptide is the start each peptide is the start position plus eight. iinplus eight. position plus eight sequenSequence [ Scer Pos Sequence Sc 69 385.9 68_YLRLKAJF 11.26 j8 V -TIEETKA 200 ,2734.." ' GLMPARAMI 1 !F I257 34217 LVV 1130 FSQLLE 1. {~7OQPSLSI __!LM F 1 10.931j I 32 _ 564I F 460 GMLTVVKKLII 131.2961 _1 [7 [VVF7V 4 10.841 -YY_ f-AV i-q.,3- l[ 8 sgII'NWVTTPT [1.857 v~o ! ,2741 LMPARAMVI 1074L T ___ 13 64675 1280.2 690AMV FVNIISNA 88564 !j8 L L i247 GUTIKEPL [0.675I~P~V 1.775 10.[468s 8 9 F _2, _ __3_i4 F210'qK Tbkl 3. 43PNA INY~j _1.764 148 FFLVIRL 0Q52 9.963 6524 DENOFT55.99 490TS FVJ 9032 each start '[17 [KE -T-l 50.389 F8 4- 681 VTLGHV11.1 len9 of tiDLe 7.652 9 anT4o 'T5 1 KVTINVDV 4[8.991 42j QLTKVSAM 72736LQAMF 1.465 1E2 4' N[A-)R RLFHI 39, [j- 47 _1 -4_. 6885 G LVKANDL D91 764 WVVIf 1.404 [K8THNEYNFY . 511 63171f80NL~vNEgv 1T399 704v SSVIVNLFV V KL4486 GVPPLTSNV 6.086 6731 ITLM KCDV 6 854: FMEKYLN :T[2 9487I L. 175 AAGT4TVVFQ 6 N R V 5RQAPLKA 2IS-LF LV 2.9 ?7 306 VFITAVV 4.242 1. 1 Ill I II4~~~I KEDKYLFT 1 L3.89 27VASGL S757NAPLFPATVj371 5 EC TVVVI-IT 39566 11 YEUKSQNI 3.453 711[E- _ Tvl49 _____ __ jVi VIL.z17 [4I5,4f[S -TI 1.04 FVNESTNA. 8.85 ___ 561 297 FLIEDINDN 3 233 E 1 TMGKY N W176211 ITVVVVIFI 3 1 -AE _ _ _ _ 8551fL 61E~~ T-i~ 1655 1 16 If 2013' FV s GIqT F 1044 9 KETEIEVSI 2 TVVFQVAV FS G 2.263VLASDG 284 =VSSPTSDYVT 2080 67 G.98 WLSNIP j11.57L~.DLAIDET :08 , 150!PSEQFL NO 0;.8c8sar poito is specifiedth F67 ~ ~ ~ ~ FVIIN. .3 TIEETA ~ 21.000 FSQLE I95I11 4339 GPAPY 1 764F II14 KLLLNFVT 10985 625~10 Vai(E5V Ejss.6 50II VLINI~SI 9 iLITVTDKDA 1 v -1 E,226 68[ qNRCIFAI C9 VLASDGGL 9 5577 KEYAIKLLA 1.082 WO 2004/098515 PCT/US2004/013568 143 1Table X- -109P1 D4v. TbeX -109P1 D~v. 1 .A021- 1Table Xl - 109P1 D4v. 1-A0201 -_A020 1-9-ers .0.er .... 1 .0-mers . Each peptide is a portion of Each peptide is a portion of SEQ Each peptide is a portion of SEQ SEQ ID NO: 3; each start ID NO: 3; each start position is ID NO: 3; each start position is position is specified, the cified, the length of peptide is length of peptide is 9 amino 10 amino acids, and the end 10 amino acids, and the end acids, and the end position for position for each peptide is the position for each peptide is the each peptide is the start start position plus nine, start position plus nine. position plus eight. * l - S L67e2 Sbrun e Score, Sco81 Sequence Score ~ 877 IFTAVVRCWY 9.814933'FD~IFL .6 314 IPLNTKiAL j0.8762 FmkCV,.6j__ Table X - 109P1D4v.1-A0201 10-mers _73ALSVTD 7 GINGvQNYEL 293 Each peptide is a portion of SEQI 31 NIFGIOVIET 8.720 ' E SILN~sAMLFI ID NO: 3; each start position is 934 CGYPvTTFEV [Y427 U,26 FsFsi .666 specified, the length of peptide is 4 1 1 PLTSnVTVFV 8,41 6 L757i AVAGtITVW 2495 10 amino acids, and the end position for each peptide is the IIQEIPLDNT start position plus nine. PV KINYILGPDA Subsequence Scr [15= ELrED 7.693 1 i8fLKq1G .3311 171~~AVI 9. [ 64I GMN6eVRYSI .[i5 211_VSiDIRYI1.30 __5j IILPDeIFRLVF 184.2157 [21LNEIVRKST 712 754LVaAT 230 [T4201iAeNV]E2 LoU Evv ~1.794J I 5001 IIDQnDSV1 .0 6 GTVVfQVIAV 'F_ 0749rKDEnD-T FTI8 16873J [0 1RSSSK:, 6.086 [ LYS[VSdCGYPV ,0881 1i1 i EFE 4.81 J29ILTNPGtVVF)V ;16.057j -371LAaGPL1208 [is ]LF A, L PdE FRL si)4§ L8 FSVPLFPaTVINI L23~[KI~sSNV 127.193, [44 I!PEnNSPGi f,5.81[67 MNAEvRYSIV 1 1.946i [1299M]LVNVTDV 115.534 )LLPL 1.8 [ F _246IE SNArRLFHL 1.860 [3:0yi VLSEnPL- NT 51.9401 j 44QTvA 4981 [11 NKiALIT_1.775~ 6 I45.911 [LNS4FG KVK3 fiI' FVNNVTNA 2 1Z-64 15481 [IL DeNDDFT 41.81[65 F L LaSDGG L [4.21 1 [61 VN 1PVI 1.B9 [Each peptid is T a portion f Q Eh2p72e iGLMp AMV 1iofS 17DNO13;eah tarApsi30.5tion s 8D N Feac [ 1.676 i 10 amino acids, and . thePn 1 faino Y- acdad h n =67 8531FSV. EQ2gYWV : oss-G2v_ 1.6421 1~1f2~Y~1,453 [601 DTDIGHV -A04 LI1 _VTTFeVPVSV [.4 [_. . . .. . I5F VAAaGIT _164 1 8 QHV - i Pv T 1 5s1 F I[ LVIYAVRC 4..27166-1 Ni~mKDV 9 345 LD~rGL 9 3[5 VIfTAVV [.2 0 nTFVAC 171 TITVvVVIFI 1I8.147 V0''NVDV 4.242 1 22 GiQLtKVSAM 11.571-. I 625I 3VLPStNPGTV 1NFGDV T 4. 2903 i ][PVtFVP 3 E9 822 LNFvT]EET 14.277 Lqg3VVDVnDNKPV K4 138 Fi G 2 N __________ I____ I _____eYS 7.101 3__] 1371 NS~LFK 1.8[ 2J bl M L6038 77 PLF__aTVN 1.953 177 flFV-NEsVTNAT [l2981 209 FTQL~aTADI 3.914 1 [620 '! CSYEIVLPST [148 1-ST73 LFV 11'4 7: '[ 7 TLMKcDVTDL1 .863 L.40 MOASGDNA{1435 [LGQPdSLFSV P.V [4 Nt EIAV .777] 8 NISIpENSAI 69 5 ........... [.2 .... . 1. . L ]F V:a V D [ 96]] r H WO 2004/098515 PCT/US2004/013568 144 Table XI 0P ~.I-Tble XII- 109P1 D4v.1- Table Xll - 09P1D4v.1 A39rA3- 93--mr A3-9-mers Each peptide is a portion of SEQ Each peptide is a portion of SEQ Each peptide is a portion of SEQ ID NO: 3; each start position is ID NO: 3; each start position is ID NO: 3; each start position is specified, the length of peptide is 9 specified, the length of peptide is 91 specified, the length of peptide is 9 amino acids, and the end position amino acids, and the end position amino acids, and the end position for each peptide is the start for each peptide is the start for each peptide is the start position plus eight. position plus position plus eight. Subequece score Pos ubsequence 37 O LIVQK 90.0001 [0.900 74 i 0,27 12 GVQNYELIK 36KOj 71_LSVV 0.0iDTLGH 024 0 DLEEQTMGK80476 LFTILAK L805 IMMKKKK 0.0X00j ILF9JL2QMMMK 0.679700MKDV .2 803 QMIMVMKKKK I 5.O 00[GIWV ~ LADE .2 720! ]fh~Ki 1 i.0~ j 1 TLINELV_.l LKR 1 0.600! 6 1_ IRoLAJI i '[23 I(NVSNIARR .0 [64(VSNS]I§Q f9FTEYF [qJ GrVr5 460 GMLVV 46. i..i [89 PLTSNVTV F 6 V RE .0 602 NVVONONK 3 00] 7[ VVj QVNj06__ APH0900QR_10.20 DL6ET7F E18.6 qFLF 3489 GIPRDEHCF fj [ -6 IFu IGo.V2= 0 1 _27 TIKEPL 15.000 RQ46 IMTVKKDK 0.600: -1j SLDCRTM [o218 1-P9 L1 5. F7 861 7 WVTTPTK 300 1 KIIKP 0.600: D633: TVVFQIAV 1101 ..-. I ..... .... .. _ _ _ .__.__....... DV] N 10 F015 QSFK 4 D I l]LLVY9. PDELIKKE R05 EK - -]- Fka[-][ 86 0TGDVPR 0.0 MIMMKKK 1500I [ LD 00L SGLRV 1.350 9 VSVT GIPsRDEHH-V 1O-84 [LL 291 NVIS DIRY1.2003 TDHEIPFR 0.300j 10 amino adnte 61] VTf73 ... 0.. 1 7 ITILQVDT 0.300 postio f IA ah etie sth L274 LMP.AKAMV 11.2001_ strpoionlunne S DLGQPDSLF S0.900 0 ILi29_VIETPEGDKIFj F0 06 8 j LLLNFVE 13191 0T80 EID N :3ea 0a270i iLsI vTPY 1.18.00 speifed the50 5engt ofSYFY peptie2is amino acidsV and T th n psto forJT eahpptd ath tr position plu e j ight.jTv~~ i iD 3- ILPD It- I. 001 1jL2 TITWWIFI 0.900nn-U 0 0=41 ELIKSQNIF 0 90000 GLMPARAMV ~ 3ss350 j 7 _PSAMLFK1.[ 5t~51 QT A KDLHAD 0.60 Fi ~ ~ ~~~~~s JT LR1[.p! 17 [ speciifed[ thsegtofpptdns ? star[ positDnpHC ni0e F-458 ~ ~ ~ 6 LTVVKKF SLDRDI 0,001 E ~ ~ ~ ~ 57 Qt -GDKjL 96c :2 LLES 0.20 I(1 B2 -VTNSP'[@:LTK:41 UTVTDPDYI PD 'IT70 WO 2004/098515 PCT/US2004/013568 145 [Table XIII- 109P14v.1-3- ;jTable Xil1 - 1 09P1 D4v.1--A3--,bAl - 109P1 04v.1-A3 1 0-mers Each peptide is a portion of SEQEac peptide is a portion of SEQ Each peptide is a portion of SEQ ID NO: 3; each start position is ID NO: 3; each start position is ID NO: 3; each start position is specified, the length of peptide is specified, the length of peptide is specified, the length of peptide is 1amnacdadted10 amino acids, and the end 10 amino acids, and the end ~10 amino acids, and the end position for each peptide is the position for each peptide is the position for each peptide is the start position plus nine, start position plus nine, art position plus nine. Pos Subsequence SPos ubsequ 57 KQESyTFYVK 16.2005 LjILFdEIFRL [0 3T TCFTdHEIPF 0.200 [~1!M iL,_W~i DAtEGDK ff0 08l 430 A AdSGPNJ29 E ]QMI MnKKKK I5.O 15__.0.600 7 _T2IAAK .[92 [ IMMKkKKKKK 15.000I Vl~TAV L~JL9 ~ '[2.000 522 I NLPRhGTVGL f0.600j451 LD(rTGMLT OL.20 14 QLIVqKELDR 12.000 467] KLDReKEDKY [12.000 '[354 { NFUETMY [0.60 :3861 NQ§aMLFIK 10 00180] MMKKkKKKKK 1000ITVvWIFI 1 t ~~!9fLP00 [091LLSnILNT:L.soR111 NGVQnYELIK .10.180.1 I ,!~~x.I7P , 80 1 RM~nMKK [0.450 1 [0JELPLdNTFVAOA I j4IIG.MN"VRYS,, 8.000.8 273I GLMPaRAMVL 8.100_12 NIFGIDVIET f0.5 217 I [ 10A80 461 MLTVvKKLDR 8.000 DYVK sENIPL F.180 357) LLETaAYLDY 8.0007 M73 UNAaVAGTI 0.405 701- S-SvVIVNL 6.750 I____ 1180 [Tl AAYLdYESTK j3.000 1424 ILQLTKvSAMDA , O ! 4 2 7 G tK F08 44 LLGPdAPPEF 3.00 0 FDG 00 5[4581 RTGMITVVKK 3.000 5939 EvPVSVH 2?JFLLN vTIETJ67iJoq 4-9 ILDEnDDFTI 2.700 F 03.150 [7-7 [YPLFPaTVINI [2.700 243 NAT7gLIT[.3 26 [ TTGArIDREK 0.150 F564I YIPnLSFDR L 2.700 L52LyG~nTRDLF 0.300 [321 ALTvT 0.150 F719j ATLInELVK 2.250 TK 9 IQPETPLNSK 2.025 I [ E]dI2 0.3001 [236 NLVSnIARRL .1 6TI GTITvVVVIF 252IIEEL~~ 4 E_.i5 i' T~Y!~205j j14LUYkGDVPL [.300l 764[72h0.13 3631 YLDYeSTKEY 2.000l7 WiFIA 1675 LMEKcDVTDLD1801 [767 VOORC 5 LPDEiFRLVK 1.800NDPvF o I Table XVIO9P 11-1 804 MIMMkKKKKK .500 631 TWKLDREK 0.3 -_-----____ , GIPRdEHCFY 1.200 LTL _0IO pr o 39~~~F 1E I[ NO 3;VPVahpetd each start SEReEKDTY 1.200 FThNEYNF position is specified, the length 763 -~ -Iof peptide is 9 amino acids, and: [0 ETGNiTLMEK 9 0.900 I 3 VVyvIFITA 0 the end position for each 613 FIVPpSNCSY peptide is the start position plus 8 FRIVKRF . 0,900 32 GIVyfYV -- eight.

143 VQKElDREEK 0.900 [2654 LLVLaSDGGL 0.270 Pos Subsequence Score 2f1 AMVLvNVTDV I900'L L [72 YEL 1 2.00i [109 GINGvQNYEL 0.810 1181 LIKSqNIFGL .0 - RVSRSSAK 60 850 DLEFqTMGKY3 L iK [ 02W FVACDSIqK [4.000 48jI IikEPLDR 0 00j [L88S I §225 [ FTILAK 36 67 FLI~dIDNA .1 0675 12411 HL-NAtTGLIT .2 58[TMLW F .0 WO 2004/098515 PCT/US2004/013568 146 Table XIV-1 09P1 D4v.1-A1101- TableX -1 1 -A Table XIV-109P1 4v.l-Al 101 9-mers 9-mars j9-mar __ 9-mers Each peptide is a portion of Each peptide is a portion of Each peptide is a portion of SEQ ID NO: 3; each start SEQ ID NO: 3; each start I SEQ ID NO: 3; each start position is specified, the length position is specified, the length I position is specified, the length of peptide is 9 amino acids, and of peptide is 9 amino acids, and he end oiinfrec the end position for each I the end position for ec pe position for each a eiht peptide is the start position plus peptide i the start position plus eplide is the start position plus! .ight.it F~ Subset F Seence Score Pos Subsequence Score 602NVVDVNDNKi300 p464 VVKKLE 0 459 TGMLTWKF6.6461 IF861 WVTTPTTFKjJ 2.000 I563j [ RPNISF 0.1801 935 GYTTFEV f.036 387 NOSAMLFIK K1 00 76 03q 46 KLDREKEDKR 1KTGADPLI 1 1.200 F 811[ St KKK0.060 762T4 ITVVVII 0.030 ATTGUTIK 11.000] 6 LLHRVLV 126 765 fTAV 0.030 462 LTVVKKLDR If0.600 4FMILK _.129 00 60P 09 N0.020 46 2 i[ TLIN _ELK 1[ 0.600 5988]ERY N D 0.L H68j EIFLVKIR0.0 r249 [_ 9_6 EPLR I.0 21 ij DADGNK § , .L0'1 YYIF' 0.06030 O 021 [if7hJAmGLv[o o 684 [ bGMAVRI [0.0665 [=800ItIMMK f 04 362 L'' ESTK EN 0.601NL- 4 SVN i0_060 =2? TEVPsV-_L-sA 0.02 805 IMMKKKKKj 0.400 L3IDDGNK000i24TVKAj0.01 IO IINI K 5K 0.060 II98 DVTDLGLHR 0.2400 I 205 [1 ITS0060 C KA 0.020 L159 KPDSPDLAR 0.200. Ij 8 KVKVE t 1 [ 9 4 6 ' S VJE6:0.20 820 DEETGK 0.20RV 0. 6L770 YKlVMV 0.20 41L60 DVQKELDR 1 0.240 ~ GRS~I 041_________ 5i7 IN- P~RI-l0.24r HLKATKN [.2000 82S[DLETYI 0.20 c n 517FYVENLR 024093 _TL![:G~yP 7F y 1006 amin acids an thjn i4 2 KAP ,f\ 00.200 jFYIK 87q I EmrK~sr___E a c pepid i R of for e pi 389 LSAMLFIKVK 0~~~O0 pepide iNt tr t itiM Vo0 plusatpsiinplsnne 781 ]Q 0.200 SS 0.040s Subsequence Score 8 SLAYK .200467 VVKL0E ( 0.04 87Ew KQE F.00 LlTVDK7 _D =5 EK=Kl =GVIIF 0:.100FT -PG [K K K S 1-0.214011 T. 0 0200 NS][PVVGlITA 0.04045jRGMTK 3:0 [J79JjjPHLKM 7 Q 0.290 1 KVKDELNDNAF [0.040 .~2 Q~MKK .0 -s1VNR? 1565K LEF 0 0.200 2.054 'F~Y.~~IF f20 794 FA L__ I ~ NO 31ech 200tpoitoni Fl T4 [ TI Y_ __ 3 GTITVVVVI 0.045spcfetelnhofeties 93LE 0VSDGYP 0.04 170 TGNiLME acdsOndten F _l ~ ~ ~ ~ 1 NSFlLT 0.0[0.40 '30§SCYP ~oo _09~~ ~ ~~ TNNHP 0 4satii~ ie T81~ ~ ~ ~~~0 NV~; q 61 .0 74ISPTSDYK 0.040 F cr FDEPR 0.200 1; SEQJK ID N: ; ac sar :D_ ~~ ~ ~ ~ oilo is spcfid th lengthF_(TgKf- C6_ _YY .0 MI5 T .00GLTVK .4 [_8_Q__ lFMR 35K G20YPVTTFE 000 TD EffRLVLSDGL f 00 [T __1 f Fo ~ooE~k4] 9 IAJVK WO 2004/098515 PCT/US2004/013568 147 Table XV - 109P1D4v.1- 7 TalIV IL IP1~v1 Table XV - 109Pl D4v.l- Table XV - 1 09PI1D4v.1 A1101-10-mers Al101-10-mrs Al 101-110-mers Each peptide is a portion of SEQ Each peptide is a portion of SEQ Each peptide is a portion of SEQ ID NO: 3; each start position is ID NO: 3; each start position is Specified, the length of peptide is specified, the length of peptide is, I NO:ifed 3h le th tar psitin is, sppecified, the length of peptide is 10 amino acids, and the end 10 amino acids, and the end 10 amino acids, and the end position for each peptide is the position for each peptide is the position for each peptide is the start position plus nine. position plus nine, start position plus nine. [p-iiSubsequencej Sc e bsence Scoe I IPosj Subsequence score [ 6.,EGPR 12057TIDSqT VIR 0,080 757 AVAqtITVW, 0.020 1L128 D DV~GKi 0.-Q0 CL48 SIQLT 0.080 7oNN::IVPvN TWy 0.020 Os3DMGR0.900 8 76 ,0.600. [§q3 LNF-tIEETK 00807 F17 74 1 VR CRq(A HL K~ I' 2 669 ETGNiTLMEK 0.600 3VEKcGIPR 0072 VNfVN 0 91 iTFVAcDSISK 0.00 F 750 1 0.020 143 OEIEK RIIE 0.600_j 1 N nYELIK i 0 255 890 IQFEtLNSI 0.600 - 1 -4 U IDLTMGK 06 - j86 SMIMMkKKK 0.400 F 805 JMMKkKKKKK000 6 - 6 9 T 361 AAYLdYESTK 00 36YSkYI 1 900[71PTmWK020 55 LPDEiFRLVK 0 8 KTGDvPLIR0I0 06 72 1181;ITNDnHPVFfl 0300 335 RVTCfT HEI[0.6-6F ;F82 IYVKeGR .2 463 TV kDRK 0 030I[TWOsENIPL _6K6 0000 FiL Q-Y-Mrn K KKKI 0,300i fF71 -T-VHT TT V.6 1 F~ IVrl:HLIVO.0n20_ L VlRPnlSFDR 0.240 t5 LRV sLS.K 6L.06 I "0 ENI0 Ij 7.QLIVqKELDP 0.240 F .4 530 GLITvTDPD 52fRYSbvGNT ff760 [TltvV 0 446 GPDApPEFSL 0.018 1683_1 G-LhRVLVK 0F4-96OAD~TMAI_.4 697 IGQPDsLFSVV 0.018j 778 QAPHIKAAQK Dc-0.200R 04 P 3 If AUdFRL 0.18 _ _is,'[ PENsAINSK 0 200 4_______________ __ 49___ RET YVW-GK 0.04 0 L 0.1 I[4 3 INATgLTI~_0200__ 3L745JSPtSD=YVKE 00 556- f FTDsQTGVI 0.0:615 _ 1 6INFYVpENLPR 0.160 74WiFTV[000SQDNO3;ecstr 2 LITkEPLDR 01603 T SLNQSaMLF4L0120 FYVKEDGGR1 0. 1 0 RVTLdLPIDL 0.120 [0[FHeNV0.31.- igt 5176[F ALRUE IFR 0.1207 VViFlTAV 0.030 [ach uequee sore 26TTGArlIDREK_ 0.10019GNVNE .2 ~ VKGVL2000 L91GRVSrSSSAK 0001 66~GNeRS.004. i7 FWVLF2.9 KKLDrEKEDK 1 0.090 6 qENFmIMKK .024 psi is 24.000 t 632f GTVVfQVIAV.J o.090 ~ 44 K~TIA .2 , 88 YWTP~2.0 [ 871 F NQ-Sa -M J] D ,_ j F E pepid isVV a 0 porio of SEQd s mn ais n ~~~teedposition for each ppiei h st oito plusid ninet ostinpls IF~ ~ ~ ~ ~~~~~~]Lussec 5L Scorei [ .1? j7E yllV .30rusqec cr RP00VNQFL 14.400 [~1 IT~gAIDR 1 9:00.. ji49 IDiEQTMK 0I2EO18 IRLVADf 4.0O INV~dNDNK0.060 8L K.90T G7PLR40.6 590 RVSDAD sSSAKV 006 U I D TO1F GN J 7?J WO 2004/098515 PCT/US2004/013568 148 Table XVI-109P1D4v.1-A24- Table [ jablj VI-= 0)4vl-A24-] 9-mers -es9mr Each peptide is a portion of Each peptide is a portion of Each peptide is a portion of I SEQ ID NO: 3; each start SEQ ID NO: 3; each start SEQ ID NO: 3; each start position is specified, the length position is specified, the length position is specified, the length of peptide is 9 amino acids, and of peptide is 9 amino acids, and of peptide is 9 amino acids, andI ~the end position for each pepideis he tar poitin pus pi de is the start position plus peptide is the start position lu peptide is the start position plus Ipu eight. eight. eight. Pos Subsequence Score s quenceSc 55T9F RLVK RF 14.000 66 STK AIq 5.280 492 SNVTVfVS 2.520 652 RYSIVGGNTI 14,000 703 F5.040 64 KIRFLiEDi 2.400 1338 CETDHElPF~ 12.000AKLA.5.0 34IFRRV .0 12I,000 440 F1 L6Y21[SYELLST -I0 400 7 DYVKiLVAA ENIPLNTKI 2.3 [15 NYELIKSQN 8 4. SQI1.50. RLVKIRFLI 1 __, 76 q TTVV 2. lU o0 09 VFTHNEYNF 10.000 23 ISFSNL9600DSDGN 0'j 69 PDSL 2.00 6 . GMLTVVKKL .RDLF 2.000 843V~f VMTDPIL =8846 . 655 _PIQGGNTRDL4.000J 65 IDG TF 2.00L 46 CFYEVEVA840 ~ 3YD~40 1 9 SSKT .0 247 GLITIKEPL .40 E 935: GYPVTTFEV~ &204521NATSL4.0 8 VDVL .0 54 EYNVEN1L .20 EL DCRTGMI P000 102 I 1 00 l~68KCDVTOGL8901!TOKKEGGj:0 204NLNVO .0 LAvIII 4.0007.5 36_pySKEA 7F50 -i~REDGEL. 18 1PFEE 1.600 43 G NAKINL 00A 558 SILVL 400 36 FPQRSSTA 1.500 356 LLEML 7.0 __ r 71[NITLINE 6 L :667 IOEYNIT 6.000 5 [VDKPF 400 Tabl VN-IO9PI [274 IMPARAMVL6.000Q -417 ENNSPGIQL 6.000Ei 314 IPLNTKIAL 6.I00 0 .60 s thLepe1 502 NPVNDTVVL 6.000 4 61a c nt 508 :fVVSE!NIP4] 6OI89NVTT~Jp00satpsiinpu ie SAINSKYTL 6.000 39 GIPRDEHCF 1.800 538 {5YDYOISIVT 6 000.5~VIPEFrOO-400 0 TPNHKLLVL .03 1 GNF 0 I 5 88396 I6QIOPETEE~F 5 6Y .000 VSN!4RLF 7315 [:PNYiK1N 90 .000 j2 SFSNLVSNI .0 1 GNKH_300135 Y~KYI7.0 [S= __ gDA]L 15000 231 LVSNIARRj55.F92J 20L LERNA IFJ2.800_ I AqPETP 1 5150 Each peptide is a portion of 5 L ,IF--I ENN~q%-SEQ ID NO: 3; each startpoions 15 ~ ~ ~ oito is, specified, the length o etcei of eptde1s0 amino acids, andthen theen position for each ppiei h TO ~~pptd is theT -L star postio plu lu nne '[--27 F ISKY LiF -9o F-oQ -ubsequenc ScoreFos1 'usqune- S~e FSVVIVNLF F500 d81&qD 7F FYKLA 23IIO INGVQNYELR -4 OL 61~L RLKOFL :=0 i~ KSSPPA 47 _jF00P WO 2004/098515 PCT/US2004/013568 149 Table XVII - 109P1 D4v.1- | Table XVII - 109P1D4v.1- VI - 109P1 D4v.1 A24 -10-mers__A24 1 0-mers _A24-10-mers Each peptide is a portion of SEQ Each peptide is a portion of SEQ Each peptide is a portion of SEQ ID NO: 3; each start position is ID NO: 3; each start position is ID NO: 3; each start position is specified, the length of peptide is specified, the length of peptide is specified, the length of peptide is 10 amino acids, and the end 10 amino acids, and the end 10 amino acids, and the end position for each peptide is the position for each peptide is the position for each peptide is the start position plus nine. I start position plus nine. start position plus nine. [ Subsequence Score _[osISubsequen- Score _ [Ps SubsequenjlScore ICFYEEVAIL 24.000 259 ETPNhKLLVL 6.000 475 KYLFtILAKD 2.310 LFHLnATTGL 20.000 TPEGdKMPQL F6.000 P 3 RVTCfTDHE 2.200_ 59 IFRLVKIRFL 20.000 654 SIVGgNTRDL_ 600 0 TPN~eNRQMI 2.160 RYlVnPVNDT 18.000 RLRPvFSNQF 5.760 GMNAeVRYSI 2.100 LFSVvIVNLFj 16.800 [01I SLFSvVIVNL 5.600 46 FTQSfVTVSI 2.100 KKYNWvTTPTT 15.000 , 1391 FTDHeIPFRL 5.600 753 ILVAaVAGi 2.100 33 RPVFsNQFLL 12.000 4 LAK nGVPPL 4.800 1630 NPGTvVFQVI 2.016 83 KPPLnQSAML 12.000 7 LAADaGKPPL 4.00 655 IVGGnTRDLF 2.000 RVTLdLPIL 900681 VTDgLHRVL 4.800 137 TCFTdHEPF 20 VTNAtLINEL 9.504 STKEyAIKLL 4.800 1. EVAlPDEIF .000 459 TGMLtVVKKL I274 TGARiDREKL 4.400 231 _LVSNiARRLF 2.000 138 MPQL KE 9.240 I 3671 ESTKeYAIKL 4.400 59YINIWTPTF 0 5211SELvl 96.000 903 IQELpL 432 556] FDsQTGV r I.800, 749 !iYVKILVM 06 5] 9.000_ 76V1iTv V ]F i 605 j[DVND nPVF 1.800 241 TGL[t2KEPL 8.400 1773 VVRCrQAPHL 4.000 6 _FAjDqETGNI 1.800 1230] NLVSnlARRL 8.400I 911 NSAnSKYTL 4.000 166 RFLleDINDN 1.800 418.400 [66TTFKpSPDL 4.000 S4141 SPEnNSPG 800 16I5 GFPQrSSTAI . 7.500 1 i11518 LnqNIFGL _ 4.000 731 1P t0NTEI i.6 .97 NSKHhIlQEL[ 7.392 6931 ANDLgQPDSL 4.000 j7 SSPTsDYVKI 1.650I RIEEdTGEIF 200 44 GPDApPEFSL 4.000 E5[AILPdEIF L__7.200 ]DNSAvTLSIL 4.000 Table XVIII - 109P1 D4v.1-B7 ___ _ _E__ rt 9-mers SGPa Y 7.200 _] LVYKtGDVPL 4.00 -mers ,[~i GF~A L:~i 75. ST~dYKILEach peptide is a portion of 2 GLM aRAV L 7.200 STdV 4.000 SEQ ID NO: 3; each start 3FSLDcRTGML 7.200 AGIPrDEHCF 3.600 position is specified, the VPPnCYEL6.00HSPKnLLLNF 3.600 length of peptide is 9 amino Gl : - -- -Tacids, and the end position forl 09 [ GvQNYEL .600 Ft KNLLINFVT1 6 acieach peptide is the start 33 NIPLnTKIAL16.000 .43 EIPFrLRPF 3.600j position plus eight. 78LHYKSaSPQPA1[ 6.000 15471 LSILdENDDF~ 3.0001 1 Subsequence|LScore V t NESvTATL E.000 952 VGQvSNTTF 3.000 523 LPRHGTVG 800.001 522 NLPRhGTVGL[ 6.000 562 TGVIrPNISF F 3.000 28 GARIDREKL 180.000 307l TVVLsENlPLI 6.000 401 DNAPvFTQSF 349 RPVFSNQFL 80.000 265I LLVLaSDGGL 1 6.000 58 EIFRIVKIRF 2.800 3 IPLNTKIAL 80.000 1661 FPQRsSTAIL 6.000 LLGPdAPPEF 2.640 - I4356 GPNAKINYL 80.000 675 LMEKcDVTDL 6.000 9 TSNytVFVSI 2.520 26, TPNHKLLVL 80.000 j202 |APVGtSVTQL 6.000 B~1ESLdCRTGME72.500 32 NPVNDTVVL 80.000 233|| SNIArRLFHL 6.000 FDGEnAKIHF 2.400 3 APVTPNTE 36.000 301]VNPVnDTVVL 6000 81 KTGDvPLIRI _2400 5 APLFPATVI 36000 WO 2004/098515 PCT/US2004/013568 150 Table XVIII -109P1D4v.1-B7 |Table XVI -1 09P1 D4v.1 -B7 Table XVIII - 109P1D4v.1-B7 9-mers 9-mers 9-mers Each peptide is a portion of Each peptide is a portion of Each peptide is a portion of] SEQ ID NO: 3; each start SEQ ID NO: 3; each start SEQ ID NO: 3; each start position is specified, the position is specified, the position is specified, the length of peptide is 9 amino length of peptide is 9 amino length of peptide is 9 amino acids, and the end position for acids, and the end position for acids, and the end position for each peptide is the start each peptide is the start each peptide is the start posioiontionplus eight. position plus eight. ubsequence Score Ps, Subsequence Score IPos Subsequence Score NPENRQM 20.000 6 LPSTNPGTV 4.000 [59 YGDNSAVTL 1.200 [5 IGGT LL000i 4.000 _ G 20.00VTLDLPIDL 4.000 667 DQETGNITL 1O0 RVLVKANDL 20.000 NSAVTLSIL 4.000 454 SLDCRTGML 1.200 3 SENIPL. 20000 123 NIARRLFHL 4.000 55 LFDEIFRV I1200 31LVSNIARRL 20.000 40 IPRDEHCFYL4.000 28I NVTDVNDNV 1.000 2KPPLNQSAM 20.0 LPAAVDPDV[ 4.000 1331 TWFQVIAV 2661 LVLASDGGL 2.00 YNFYVPENL 4.000 281 MVLVNVTDV L.T00 92 SAINSKYTL i2.000 117171 TNATLINEL 4.000 YVKILVAAV [000 [403 APVFTQSFV 12.000 47 GLITIKEPL 4000 766 VVIFITAVV 11.000 378 AADAGKPPL [10.800 1 INGVQNYEL[4.000 90SVSDCGYPV[11.OO0i 116 FPQRSSTAI 8.000 757 AVAGTITVV 3.000 j486I GVPPLTSNV 1.000 745 SPSigVKI 8 000 -3 IAVDNDTGM 1 L.goo_ 75! V YAV9.000 13E84 [PI -M 8.000 1 [IPENNS .400 [300fIVNPVNDTV 1.000 L6IHPVFKETEI 8.000O L23 PVGTSVTQL-2.000 KVTINVVDV 1.000 VPSIDIRY 8.9000 '[06 LPDNTFVA 2.000 2 IL 1.000. TPLNSKHHI 8.000 94I SVH VLASDGGLM 1.000 _ 29NS6 LDIRYlVNV 2.000 704 SVVIVNLFV 1.000 888 FQIQPE P 600 0[20 287D N 273 GLMPARAMV 0.900 4 APPE SLDC 600 350 PVFSNQFLL 2.000 278 RAMVLVNVT 0.900 ENNSPGQL 6LVAAVAGTI 2.000 9 NPENRQMIM 6.000 4 DCRTGMLTV 2. Table XIX-109PID4v.1-B7 AAVDPDVGI 4.000 NVTVFVSIl 2000 -- - e NT 14487 VPPLTSNVT 2.000 Each peptide is a portion of TPNTEADV 4.00 ___ ~ .SEQ ID NO: 3; each start DGNRVTLDL 4.000 II EVAILPDEI 2.000 position is specified, the FNPG 4.000 948 HTRPVGIQV 2.000 length of peptide is 10 amino acids, and the end position forl 7I MPARAMVLV 4.000 847 LPIDLEEQT 2.000 each peptide is the start 4d GM.LTVVKKL 4.000 L VSRSSSAKV 2.000 position plus nine. 274 LM AMV 000 I88 ASPQPAF~l 1.800 Subsequencel Score 6 1-SNCSYELVL 4.000 5I AAVAGTITV7 1. 223 5 .83DSDN I 4.0080W 202 APVGtSVTQL 368! STKEYAIKL 1 4.000 I2f GGLMPARAM 1.500 1 200.00 P167:FQRSSTAL 4.000 1453 FSLDCRTGM 1.500 3 rQAPH 0 .54 ILPDEIFRL 4.000 78 KCDVTDLGL 1.200 615 VPPSnCSYEL 0.00 31sPG19LTKV 4 4.00 243: NATTGLITI Fl[i 0 PNAILL 80.00 KIRFLIEDI 4.00 D11 DPDVGINGV 1.200 11:[RPFsNQFL L L36]l FLLETAAYL 4.000 69 8 QPS LISV 200 M 5 PHgTVGLI 0.000 WO 2004/098515 PCTIUS2004/013568 151 TrableX- 109P1 D4v. 1B7 j[Table XX - 109P1 04v.1- 1Table XX- 1O9PID4v.1 I 0mers j jI 3 3501-9-mers fI B3501-9-mers Each peptide is a portion of Each peptide is a portion of Each peptide is a portion of SEQ ID NO: 3; each start SEQ ID NO: 3; each start SEQ ID NO: 3; each start position is specified, the position is specified, the position is specified, the length of peptide is 10 amino length of peptide is 9 amino length of peptide is 9 amino acids, and the end position for acids, and the end position for acids, and the end position for each peptide is the start each peptide is the tart each peptide is the tar position plus nine. p plus eight. position plus eight. SusqeceSoe[Pos, Subsequence 1Score '~os Subsequec cr -Subsequence, ScoreF.T7 FPos _TAIj 20.000 j8 DENDDF 3.000 138' LM:PQ§L~VKEL 80.006j 281 lr-R-IDREKL F13.50 11 5211 VAILPDEIF 13.000 RVPDL 2 0.000 TVVLEK 20.000 133:KP~nSML 0.00 7451 SPTSDYVKi 12.000 12671 LSDGM .0 LPIDETAM 20.08NPENRQMIM 12 E V S YK L 80.000 DIRYI ~46JF~pESLL3.0069 AVNTG 2.0 _f 6411 KR L 2.40 I1132TPEGdKMQ 2.0180KAPQQPF 1.00 55 LD!L2.400 307 TVLSEIP 20000[18IKVKVE D GG F 9.0291j NVPSIDIRY 2.000j 7f PIDEQM 000jI6'18 O2 223j KIHFSF SNL 2.000 5 LYtDL]f20.0001 7321 APVTPNTEI 8.000 DVSSPTSDY 112.000 1 481l LAKDnGVPPLJ[ 12.000 ALFPATVI FH00 j 71 DIND LF 2.000 AILPdEIFRL100181 PFTEI 3? _71 !Da-KPPL 12.0001 IiF9STl 8O0 L4VLLIL 2,000 [5MLAA a 0000 59 TGMLtVVKKL2.000 - -~-- - -136 STEYAKL .00 61j IPFNCSY [_2.000 Table XX - 109P1D4v.1 TaleXX O91Dv1-1 32 VSNIARRLF 5.000 435 SGPNAKINY. 2.000 B3501-9-mers -] - Each peptide is a portion of SEQ ID NO: 3; each start 5.000 [2 ASPQPAFQI , L1900_i position is specified, the 6 LPLDNTFVA 4.000 1 PSNCSYEL 2.000 length of peptide is 9 amino acids, and the end position forl 63 NPGTVVFQV, 4 1 F1141 E' 2.00oj each peptide is the start 11k261 LPSTN 40jy position plus eight. I C vrKlu I iLQYJ 2.000 Posue uence[_ScoreRSSKT 4 OOI., IPRDEHCFY- 360.000 P 00 5LKPQ PEFSLDCE4.000 l000-J LTKVSAM 2.000 1oLPRHGTVGL 60.000 147 L 00-_ 171 SPKNLLLNF 60.0006 40F 72.000 j 17961 TPNPENRQM 60.000 SPVFTHNEY 40.00 10[AVTQ] 4§O I__ I RPVFSNQFL, 00025MAAVV .0 68 VVAD .0 F NPVNDTVVL 30.000 [PVN 2.00 871 DSPDLARHY 20.000 92 SAINKYTL 4.000 4 1108 DGIAPQP 2.000 IPLNTKIAL 20.000 j51 EF H 5 TPNHKLLVL 20.000% VS4 SSKV 3.000 j WyNANK 2.000-1 1451 SLDCRTGM[ 20.000 | 143.6 -PAIY if 20.00 NE Y12 NPFQFI 3.00 1 11 DEKDYI1.0 EQ I ~D --- F NO: 3;ec1tr position is0peifidth M4655 IPFRLRPVF 20.000-0- WO 2004/098515 PCTIUS2004/013568 152 Table XX- 109P1D4v.1- jTableXXI-109P1D4. - Table XXI - 109P1 B3501-9-mers I{ 3501-10-mers -J3501 Each peptide is a portion of Each peptide is a portion of Each peptide is SEQ ID NO: 3; each start S I . N each start SEQ ID NO: 3; each start position is specified, the position is specified, the position is specified, the length of peptide is 9 amino length of peptide is 9 amino length of peptide is 9 amino acids, and the end position for acids, and the end position acids, and the end position each peptide is the start for each peptide is the start for each peptide is the start sition plus eight. position plus eight. I position plus eight. SSubsequence Score APVGtSVTQL 20.00 4f0- REKEDKYLF 1.800 L -A 0 610 395 KVKDENDNA 1.80020.00 P -9,l__ -0 0 74511 SPTSdYVKIL ____________ __ 596 SAKVTINVV 1 800 .- - 20.00 87LFVPPLtSNVTV 4.000 837DSDGNRVTL 1.500 0 ___ _DS G VTL' - 166~ FPQRsSTAI1L 0 26fPnGTV61 95 ISITLPAA 1.500 I 06LPLnTFVC 4.000 19231 SSSSDPYSV~ 1.500 L i0661FAqENI301 508) VVLSENIPLj 1.500-11 0 741SPsDVI300 9061 LAK~nGVPPL 0'7(0 1.500 897 7 -11206100i [~jGIPRDEH-CFJL1.500 NKhIEI10118 I~NFL300 '96 VSIPENAPV 1.500 _300 7 FDREKQESY 1.20007 QAH_ 3.000 4681 LDREKEDKY 1 :~0j1[P~LNv[0J~92.P j6981QPDSLFSVV 1.200 8.. FTTGML 481f____P , ___ _ _ N SKYtLAV 300 243NATTGLTI 1 200 -- K SIFVVI 3.000Q 0[i 6 DDNV 2Sn 0 Table XXI -19P1D4v.1 -I B3 51-N LTNEY 1 RVtLPIL 2.000 Each peptide is a portion of I 91TNeRM .0]I68 I~NTM200 SEQ ID NO: 3; each start- _ _______ position is specified, the LJFAVNS .91L~ S~FLV202 length of peptide is 9 amineo347P~~AI. ~P0 I P~IET90 acids, and the end position £3 P~VQI800 11FVpNS .0 for each peptide is the start____________ position plu eight. 84TPsHHIk9].76ALpTVN100 Subsequence Se _ S~EDF~oIi 21SGqTV 200 KPPKKn[1AML 847 LIIT 1200 461 GPD~pPEFL '609 945 3S1tPI200 ______ 000__ [tq83.

1 KPPDyqnQSAM 1.20 1341 LRFSQF .00 l5NPlD l 20]0 -~ ~~~43, 0 L PKIM 6.0-0057SV YN200 ~1DPYSvSDCGY ________ 39[RPVFsNQFLL :00'11rHPnLN.50034 PRRVS200 L. . J , 1 NA~nKYT ~15.00 2875 MPA-MVLV 2.0001 521LPRHgTVGLI361ETeAk5001'71 TaPPN200 length of'U: a- petdFs2 mn 1138 MPQiVQKL 2000] 2~] GS~sSDPY4.0$84!211F DIGWnAKIH 2 o000 E~~fo ach peptide is ah pottarft--_8 position s specifposithion pfluIS eight PVf --- tSVTQLF v- F--6 lengh o pepideis 9amio 745F SPT dYVIL i~ ~~ FPO TALN F 9 o [2, jLltT12 LAK 00 4nGVPPL2 9q 120.0 10.00' 847!EPIDIEEQTM50 NS' PP fNLEY6009 00:: __ 20 77i TPNPeNRQMI OOO !F_] NFV 0000IN~F~R Il~yFTPL~dsKHQ--il 8000]-o [92 54 LSIY~dENDDF 000 0~~~3 TKyAI 6000,12 GQtVA:.00 ]40.001: 4461GPDS pPEFL j.O i' 060IlRVF F349.5 HSPV~nLLLNF 5F F000 NA4SKTL0.0 [523...1'!1 PR TV~l 367 ESTKe-AlK 5--79KTa00P [.0 9 YPV(TtFEVPVJ50 :[36GPNAkiNYLL :F 0 PCT/US2004/013568 O4Tabl Ae I-0Pv .1 KB3501-10-mer -13 ~ ~ ~ ~ ~ ~ ~ Ec peptided is a porio ofq--l71Ll~( f 2C WO 2004/098515 PCT/US2004/013568 153 Table XXI-109P1D4v.1 - Table X-109PID4v.1 f Tab B3501-10-mers A e__ ________________0-mers 2 .- Al-i 0-mers Each peptide is a portion of Each peptide is a portion o Each peptide is a portion of SEQ ID NO: 3; each start SEQIDNO:3;eachstar SEQIDNO:3;eachsta position is specified, the position is specified, the length position is specified, the length length of peptide is 9 amino of peptide is 10 amino acids, of peptide is 10 amino acids, acids, and the end position and the end position for each and the end position for each for each peptide is the start peptide is the start position plus peptide is the start position plus! position plus eight. nine. J -nine. I17 DVGInGVQNY 0[700 2,500! 779 APHLkAAQKN[4500 6 d.0 6I TPNLV 206 ETGTLMEK 2.5OO F73C [ TPNTS eIADVS 2.000: [ DSGPnAKINYroj J-2 TGElfTTGAR 2.2501 1GGmARM20 2 LLGPdAPPEF 12.000 1 TSNVtVFVSI_[2.000 3iQI LSENiPLNTK 931 VSDCgY VTT :1.5001 2.0000-I L9 0 311 _____NF :L 4 Q63VYLDYeSTKEY 00 SPPTsNVTV0 ATDAdGENA fl7321 APVTpNTEIA 7: 2.000 AVDPdVGlNG 209I TDTnDNHPV [5L DPDYgDNSAV EEO I 1 :K 1 8 T-DvPLI =1.6001 160J[KVE~gFQ [ 7981 NP~Q IFi115 569 SLEKQES__1.500 18.00 L[ETE0eVSlPE [1-12 53 AILPdEIFRLEDgGRVSR [ LO TVVLsENIPL 1.5001 1. - 1.000 78: 269f ASDGgLMPAR 7 D [AC ___k __N _._........... ............. r I432 DADSgPNAKI il~ 1[ LSSsDerSV I 92;jjSyV [1.59 1 Ff55f LPDEiF7RLVK 125LI~~_DAIDIgENAKI Ji 000q 301:_VNPVnDTVVL 500 591LVSRSsSAKVT 503jT2YD~125 8~DL~RLKj0 80 .LAGIPrDEHCF :1500,6RTG 1 1.000 861TTFKpDSPDL150i_1_RIdTEFj3gGLvTPY f0i 1840: __ ! 54 \/DPdYVSD 7250 '_ __ _ [GNRVtLDLPI I RVT 1.000 L401]PRDeHCFY_120 3'FD IFL6 .5' 139jKEdAV .0 I 9jKANDI~&~120 t~iDVsDRY 1.5!V.7 !tAP [471KDReKEDK 1.0655 Q~TYK 540 13 I~IEA 090 REKeSYTF 0 61qFSS![ IX- 109P1D4v.1 - 6481 NAE SIVG 450 A1-10-mers Each peptide is a portion of3.0 SEQ ID NO: 3; each startT TVI position is specified, the length of peptide is 10 amino acids, [41EDeKT .0:53FN~PFH_[65 and the end position for each !4 TMER petd stestart position plus___ _ n250 F5 446! L GPDpPF peptid is thnine. 491 LEachpetidei a portion 91!of~SO .0 positionE-L is5 spciidth3ent f41[ :RV7p Sb equence - Scr [FT .~I GLII.500 j KDItDGL 1[ .0 P DSGn AK18 ETn L54001 . . N.... ATffsl,.NLD _eSKE K64 .AE V~gG SR F AASD1gLMPAR 1250 559i FTDAelRL 6.250APFS 0621 Su5s5qKeEcyTFYVK IIOO] E8I NAErYSIVG 1500 LLELDanDDFT 225.

WO 2004/098515 PCT/US2004/013568 154 Table IX- 10911 D4vl - Each peptide is a portion of abe VII-109P04.2 Al-10-mers SEQ ID NO: 5; each start N'terminal - A-9-mers I position is specified, the length Each peptide is a portion of of pEptid pepid amin acidsioandf SEQ ID NO: 3; each start tendpsiofreahSEQ I D NO: 5; each start position is specified, the leghppieiIh satpsto ls position is specified, the length of peptide is 10 amino acids, eiht p of peptide is 9 amino acids, and and the end position for each t end pstnfea peptide is the start position plus Pos' Subsequence score peptide is the start position Plus nine. eght. I DIGEnAKHF 0 [ LCGLIQQTV AILPdEFRL 0ii IQIFQVLCG 0007 _STNPgTVVFQ 0.500: L PTDSRT 0.025 l2481L LITlkEPLDR 15 500 jr 21 [QQV:TSVPG 0.003 I 51EKDTyVMKVK 0. 00E 8 7& LIqIFQ 0.003 ,I4301 AMDAdSGPNA 0RQWVIQI if 0.003 _ _ __ E _______T I71 CGLIQV .0 38 KADDvDSDGN O.5OOY T S 0 [2731 GLMPaRAMVL ~1 SP~e~hN ~ 4~7~PVSVTRP 0.01 TVSVPMD 0t. _lQQPeTPLNS 00_ 564![ VIRP nSFDR 0.500 _PnlSMFRTERQWDLR 0.001 4 M119MLT~KKLDR .500 E2 [ii TCFTdHE!PF 0500DSRTS 5001 lDQnDNSPV 9[50I _ [ SDLLSGT 0.0001 DAPPeFSLDC 500QQ 140, QLIVqKELDR 00Tabe Vil-9PD4v.2 IAl -9-mersal il-10P ~. [101DVnGNY.050 N' terminal -A--es I TbeVI-191~ DVGlnGVQNY 00300~--. 52 VAILpDER 500Each peptide is a portion of SEQ ID NO: 5; each start Eahppiei ap ino E ThiGTITvVIF 0.500 1Ec etd saprino E TTO rD !-V F 057 ~~position is specified, the length I O ;ec tr oiini 9201 KCSSsSSDPY 500_ _C~SSP 1 0.500' of peptide is 9 amino acids, and specified, the length of peptide is [~8l SA~qPFQI o.o0,the end position for each 19 amino acids, and the end peptide 881tion plus position for each peptide is the IF VVD~nDNKPV 5001 s posiion plu ht. 161 TTGArlDREK 0 500 s [Subsequence Scr Po Subsequence core [sii DVDSdGNRVT 0.500j 2= GMDLLSr74 .500 I[37IKSEGKVAGK 54.000 [6I3AIDQeTGNIT 50 5 5TO1:75q [1321 TPdKMPQL 0502 I KEPIDREET 5145 HSDA 3.750 VNESvTNATL 0 450.6 2 77!. QAPHIKAAQK I0014iQLLIQ 000[15NCELY 25O4 9 VSIeNAPVG 0.00TS 0 2.50 SQSAMIFIKVK 000 0.050 871 DSPOITHY 0.3008 F1 12 86 E ISIPeNSAIN 0.300 0.020 872 SPDLaRHYKS 0.2502 0013 I 1120 AAEITVQPT 1 0.900 55 DDdDGR0.2500.1 833,1 AODVdSDGNR 0F5 197 .1LIPQTsv . .10I32[AsDNcTQECE:0.750, [ - F vLI(lQYL 0.10f62 :SSDGGLGDH 1 0.750 LTable VllI - 109P1 D4v.2 ____ C'STerminal-Al-9-mers I N 5;] each st L415 LGLQT0.010 1 T151SDsSSqI050 of ~ ~ ~ l~ petie s ain aid, n WO 2004/098515 PCT/US2004/013568 155 Table V111 -I109P1D4v.3 Table V1I1 - 109P1 D4v.3 Al -9-mars A1-9-mers IL TbeA II19P1ers Each peptide is a portion of SEQ Each peptide is a portion of SEQ Each peptide is a portion of SEQ ID NO: 7; each start position is ID NO: 7; each start position is ID NO: 7; each start position is specified, the length of peptide is specified, the leng specified, the length of peptide is 9 amino acids, and the end 9 amino acids, and the end 9 amino acids, and the end position for each peptide is the position for each peptide is the position for each peptide is the start position plus eight. start position plus eight. start po ion plu eight. SFbs S core IPoK Sequence F Score '[ Subsequence Score 25: TMEIWIHPQ 22 LVQATLI 0.050 0.020 SVHTRPPMK 0.400 77 STSHGL 050 F 0.020 110 ESTFIPGLK 00 240 .O3SPPLIQ 2350 7TQECLYGH 07_ 6 LOHS PIQ 0T E 0.020 M[SPTMKEHYR 0.050 1261 TALSPPS 0.020 5 LPEGSQESS 05 118 STHH 050 [i6RTEGDGNSD J0.225 J 446 LAQAAAISH 0.050 :0~LHPPQ .2 HSPPQ_1 1121 OAASALCH 2 0.050 166i GLG A2 SHSPPSAQAS 0150 32TFTPRQQAR 0.050QL .020 2I1 HsVQAT 0.150 1 8 PLGYPQEEY .050W K7T7 A inSSSTQHSR~ 5 12821 GiOOLOSVD 0ASIO___ 19 IHSPPVTQTI O ,5 ilI7O PI'PIOVSA 0.050 al II-0PDv I-[L SPPIQVsLO0 ISO 1- KEVVRSCT k .O I5 - 9-Ders I 17 PL 0 0.045 11.9 HPPSQSJ0150C j-K 88 QEEYqpDDAGT 0.025I0 ; ahsat oiini [242 YSPPLAQAAf 00 F2 VE EC E.45 s ti9, SESDGG[ 1__ 13 LVVRSCTPMK I11i ViTQTALCH J 15 SDQGQY v0530foeahptdeitestr j136 TQCIG[0.125 1S SSSSQAA 0.030 ' 1 o usqec cr 67 H0.125 2 SIQ 0.030 294, QGSATSQFY 0 125 SSSQAQASARR 0.030 1SQAVSVHTRPPM 005 86 LYPQEEYFDR 052 1041 MSERLHPSD 0.027 I QQRT .0 I DHDAGSLTS 0.2 1iPLTTTFTPR 0.26._PSRVT .03 ILF VTQTIALCH 27 ATSQYTMS 0.025 [ 258 LPQVIALHR I'0.125 CWMASLH4902 331RGDSPMEEH~ 0125 5U HTRPPMKE 0.025 1 1s PPSRV 000 16 10CPKS L..100Q (05 GNSDPESTF 002 l KVIPLTTFT 0100 5 ATPSNRTEG 0 Table i-19PID4.4 07 LHPSDDS 0 I2. HSPPPIV 05Al--mers ______ STTEIWH '7025Each peptide is a portion of SEQ I TQOPT -EEA O.100 STEWI _ 4 KVAGKSQRR 0100 ID NO: 9; each start position is 242!F CPMK-E- STT 0.025 i specified, the length of peptide is 9 PSD D SI amino acids, and the end LTTFTPRQQ 7 TSTSHGLPL 0.075 TTFTPRQQA 0.0 2f95 GSATSQFYT I .0.075 I ~ 5ALHHSPPLV 1 .2 poinfor each peptide is there 0.12 7!C-S~q9TQ7GF-P-P o stagition pl egh ilj Ec QEql- G 1 ![ 'qT, F S 0030' Pos Subseence Loe 2521~~ -4-' F-- -' - -, 3 WHPqPQSQR !1,201 E8Q605I 6L .9 7 SALHHSP 02050 301258- SALYSPP 0.0 A::G LTS ~~ HS--,[ -- HhGH GS I0.020 specifiedPA§LD th lehP ofpptd1i FL 2 DfH-aD55k-[H25 F3 O7F -LHSDs, 6 16 206 F -HSPPQV -0L02 Al-P0-erSs [00 F4TI KVAG SLR -J "FTPQSQRRT 0.02 -1 9 -specified, the length of peptide is [ L- P§-I F 'P- F--TTT- N--Q-1-002510 amino acids, and the end position for each peptide is the P-21 25start position plus nine. oTs jjSubseguence 3= 1WIHPqPQSQR 110 5§§SHSPPQ~j 0.075 16)ACSPL .2 D-I-!SS 0.0[20 7 WO 2004/098515 PCT/US2004/013568 156 Tab le IX - 109PID4 v.4 Table X1 - 109P1D4v.4 Tble XIV - 109P1D 4A Al -1 0-mers A0201-10-mr Al______________ Each peptide is a portion of SEQ Each peptide is a portion of SEQ Each peptide is a portion of SEQ ID NO: 9; each start position is ID NO: 9; each start position is ID NO: 9; each start position is j specified, the length of peptide is specified, the length of peptide is specified, the length of peptide is 9 10 amino acids, and the end 10 amino acids, and the end amino acids, and the end position position for each peptide is the position for each peptide is the for each peptide is the start start position plus nine, p satpsto pls in.start position plus nine. psition plus eight. ;±s],LSubsequece jScore os Subseeencn P sc Ssequence co ~jT1 PQ~qSRRVJ~025J QPQ~RRVTF 0. 001 4 PSRR .4 ~f4HPXpQQa,_ 7.O5 IIPQSQ 000§ QSRVF 0.00 '[j] ErLHPQpQSR00 065 )WIHPQPSj0000 Tabe IW-pP10~9~.4o al I-0P ~, SR .0 6 FP _sRRV 0.0008 Po4 5IQQRV .0 Eac Eachtidptise isaoportionoofSSE 1 8,Q~RTHl~~IID NO: 9; each start position is I IIPPS .0 speciiedihelegtheolpepidehiof1 6eptideVT 00009 Tal 1OPv4-amino acids, and the end position_____________ 1for each peptide is the start idispoS position plus eight. - T A - ____" AIO-l-mr I SN:ubeastatpseo i o usquence_ Scorei ~ sRRTF 00005 =[q]LQR [QPSQ [0000 sEach peptide is a portion of SEQ aminoL acids, H and00 the en oiin3 HQQ .06 pcfet ents of [peiei ID NO: 9; each start position is specified, the length of peptide is LV 0.00 10T beX - 0 P . amino acids, and the endpoioni....... positionpoii for each peptide is the the ois p Susqec Score 0 positionplusnn. Is NO: 90 e start 10.00ion Subsequence i e: 8 QSQRrVTFH 0.006 o pties9iQS 1 0.00 3 WHQPQ QQR iL.IIOSIPQQ R 00o ~ 7~Q~RVF 002 L7YiL IHPQPQSQR 4 0.000 - Table XII - 109P1D4v4 4 77 QQrTH .0 If I IWIH PQPQS4 0.oooj A3-10mers EIhQQSfio Each peptide is a portion of SEQ ID NO: 9; each start position is for each peptide is the start specified, the length of peptide is 10 amino acids, and the end ___:: 0-mro s positionn for each peptide is the start position plus nine. Each[D petd s qotono E ID Q NO: 9 each startVTFH position is00 Subsequence ScoreT A3-9-rnerss F---1 ami QS acds and 09 th endqPSQ 0.0801QRIf specfie, te lngt ofpepideis - - -Each peptide is a portion of SEQ postin fr ac petie i te ____ QP~qRVF 002 ID NO: 9; each start position is -~ tar psiton lu nie. QQ~rTFH_ 0.13specified, the length of peptide is if os ubequnce Scre 1 ,EIWhPQQS 0.091amino acids, and the end position _________for each peptide is the start [ 9 [ QSQ~rTFHL 0.809 7~l psitonplsiht.04poionluegh V71 WH~qPSQR o~og :Pos12Subquence_ 0Sc2 e f 7 usqec cr QSQrRVTFH 0.006 2- -66WPQSQVTIHPQFpq QPQsQRRVT Q0.00P T 0 Ef -i - L PLP9PVTSH0RRV1; F-T jHPQQSQ 0.00 [ Table Xi11 -109P1 D4v 4 Each peptide is a portion of SEQ -Q _- F!0 I ID NO: 9; each start position isE specified, the length of peptide is D [,,wlpPS .00 able X - 1091 D~vA10 amino acids, and the end.0i A020-10-ersposition for each peptide is the start position pu nie.... Each pptide s a prtion f SEQSubsequence al X 191~. ID O: ; achstat osiionisI TC -- QSQR n HgQSQRRFL 61 S~ubseuece coel IW~PQQS .091 reach peptide is h o artioSE EE F-9 80gj EK: .004position plus eight. QrRVTF D.Oq os jI Subseguence So T.- 7,1~~~~ LlHPQPQSQR 0.904 --Q§ I L QSQRRVTF 0 El~lhPPQS [q~qO [- WiHPQPQSQ 00 qSQRV 6 QSQRVT PQLPgPQSQR - -ies W8 1 PS~rVTF 11E ll~pQPQQ--W IHQPQS 0.000 _,Pq QsQRL L0.0000fq Tabl XV QR -19 1 v.4 WO 2004/098515 PCT/US2004/013568 157 Table XVI- 109P1 D44 TableXXI-109PIDMA - A24-9-mers F Table XIX - 1 09P1 ID4.4 B501 -1 0-mers Each peptide is a portion of SEQ Each peptide is a portion of SEQ ID NO: 9; each start position is Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 9 IDNO:9;eachstartpositionis specified,thelengthofpeptideis amino acids, and the end position specified, the length of peptide is 9 amino acids, and the end for each peptide is the start 10 amino acids, and the end position for each peptide is the position plus eight. position for each peptide is the start position plus eight. Pos S0osu enn_ 8I_111 QSQRRVTFH 5 i [V: qq 1 IF WIPPS F.014iHQqQR5 40 6 I PQI QRV k-p( g pio 1:0 [ __L PPQSQR 0..02 7qPQQR .010] S W HPQPESQ 0.3W 8 KIH:QP PSQRQ 600 Table XVII - 109P1 D4v.4 PPSQR 20.001 A24-1 0-mers V1] P sR 0.91 Each peptide is a portion of SEQ 8 1 PQSrRVTFH :00l1 ID NO: 9; each start position is specified, the length of peptide is 12 1 WHpQPQSQ 1 ,[ .1 I -Table VIII-109P14.5 10 amino acids, and the end 0.001 position for each peptide is the Each peptide is a portion of SEQ start position plus nine. Scorel-Table XX- 109P1 D4v.4 IDN:1;ecsarpitos Pos Subsequenc e specified, the length of peptide is _________- -9 amino acids, and the end S QSQRrVTFH 4001 position for each peptide is the ] QPQSqRRVTF ID NO: 9; each start position is S HPQ SQRRV specified, the length of peptide i CQDWIQRQVgSQ OnIE amino acids, and the end position -...... 7 -Syi .... c......-r I EIWIhPQPQS .00 for each peptide is the start 3 ) SVTRPSQR ;0.100; 2 II~pPQS .1.011 I. osition plus eight. . ~ ...... VT. .. 0050 ![Lfq PQ~ QRRVT [0.0151 11 ___ Subsequence. Scor [0 21 MSH S . L PQPQSQR QPQSQRRV 17 [ 0I.QS O0.20 PQSQrRVTFH 00PQSQRRVTF 00 8 _ SQRRVTFH [9050 ._i11 001 Table XVIII - 109P1D4v.4 5 PQPQSQRRV - 0.0M L B7-9-mers- F l WIHPQPQS 0q.010 Each peptide is portion of SEQ _ j___WIHPQPQSQ 0.0101 -9 4 ID NO: 9; each start position is Table IX specified, the length of peptide is 9 I IHPQPQSQR 00 - Al-I0-mers amino acids, and the end position Each peptide is a portion of SEQ1 for each peptide is the start Table XXI - 109P1 D 4 ID NO: 11; each start position is pL _osition plus eight. _j B3501-10-mers __specified, the length of peptide is 10 amino acids, and the end f P ubqec Each peptide is a portion of SEQ position for each peptide is the SID NO: 9; each start position is str oiinpu ie. positro plusio eight.i III0.20 I specified, the length of peptide is s1 9 amino acids, and the end S q S D iLPQPSQRq9gRV 0.020 1 position for each peptide is the F_ 3 SVHIRPSQRJ 01 8 QSQRRVTFH 0.010 start_____ plight. .2 WHPQPQSQ 0.010 ubsquenc SsQRRV I17 11PQSQRRVTF 0.003 7 T IWIHPQPQS 0.0030 TabIe XIX - P1DSv. F_ 1 mino F a ids , an th end F7~~ ~ ~ QPQLqRRVT -0.6001 P F qs~~~~ EClPQQ LR 6.030y~s_7 E WO 2004/098515 PCT/US2004/013568 158 Table IX-109PID4v 5 Table XI-IO9P1D4v.5 Table XV-109P1D4.5 Al-10-mers A0201-10-mers AllOI-10-mers Each peptide is a portion of SEQ Each peptide is a portion of SEQ Each peptide is a portion of SEQ ID NO: 11; each start position is ID NO: 11; each starposition is ID NO: 11; each start position is specified, the length of peptide is specified, the length of peptide is specified, the length of peptide is 10 amino acids, and the end 10 amino acids and the end 10 amino acids, and the end position for each peptide is the position for each peptide is the position for each peptide is the start position plus nine. start position plus nine, start position plus nine. SPos S ubsqnce sc o re flo s1 Subs-quyenc Score I Pos Subsequence I ScoreI CL F till RPSrR T (1003 TRPiQRRVT- 0.0 ff41) SVHTrP QRR 1 0.400 2 PVSVhTRPSj002TPqRT~OOQ ~ jSHRSR 1 0 PS5r H RPSQrRVTFH 0 Tabrl Table XX1-9PD9PIvD4v.5 L TRPSqRRVTF 0000 V-HTRpS-QRR 1 000 A3-9-mers 5 0.0 -F- 2 ~ PV~TRPSQ 0.000 lEach peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 91: PSQRrVTFHL a bleI-9 P1 D4.5 amino acids, and the end position Afor each peptide is the start Each peptide is a portion of SEQ poito plsegt5~J VTpQR position plus eight. VTpQR .0 ID NO: 11; each start position is Po seqenc ,Sbeqec Scr specified, the length of peptide is 9i ____ SusqeneTScr I [: ble XVI-109P1 D4v.5 amino acids, and the end position [T4001 for each peptide is the start RPS ____ 0 T V A24-9-mers position plus eight. ---- -- _ -K o o. Each peptide is a portion of SEQ ID Po usquence ore_ i!,,---- . LHR NO: 11; each start position is _____ -1 -5! 5 HTRPSQRRV .0021 specified, the length of peptide is 9 3 ~ VHTRSQR[9O1 amino acids, and the end position for 5 LHTRPSQRRV ooq ~ iLPQRTH __ each peptide is the start position plus SF 00 VSVHTRPSQ eig TRPSQRRVT 0.000, 61TRPSQ 0T00 4 TR0R00' 0 i TRPSQRRV 0.0 Table XI-109P1Dv6 6 RPv.5V AP0- 1 e A11-9-mers if 4 i ' ------ --- 2 VSVHTRPSQ OOl, Each peptide is a portion of SEQ 7 T 0 1D NO: 11; each start position is E__ Table XI-109P1D4.5 specified, the length of peptide is 93 SVHTRPSQR 0 amino acids, and the end position PSQRRVTFH S a s for each peptide is the start IEach peptide is a portion of SEQ po!to plu eih 4 VHTRPSQRR 0.001 I tNO: 11;eachstartposition isplusnin specified, the length of peptide is Subsequence _Scorei SVH~PSTab0600 XVII-IO09P1 D4v.5 1 5 VHTVpSQRRV 6 10 amino acids, and the end -76ii 2-1qmr position for each peptide is the HtRPSQR 0.0301' start position plus nine. -Each peptide is a portion of SEQ Pos Subsee RPSQrRVTFH FO I ID NO: 11; each start position is TRPSqRRVTF 0.002 specified, the length of peptide is It _10 amino acids, and the end VHTRpSQRRV 0.016 1 position for each peptide is the E006, HTRPsORRYT F100: startposition plus nine. B ~ R P S ~ rR V T H _ _ _ _ _ _ _ I__ _ Tq S bseq uence , ' :S core i SVHTrPSQRR 0.001PSVT VPVSvHTRPS QRrVTFHL 0.840 5 jVHtRSRJ000 -' T RpSQRRV jq 0.00 71LTRPqRRVTF_ 0.00 1 VS~tRSQR [(1001VPVSvHTRPS =0.150;.1 IiD N 11; each start poiini LEJL SVHTRPS 00 120 WO 2004/098515 PCTIUS2004/013568 159 Tb T9PI Each peptide is a portion of SEQ A24-1 0-mers 1 7-1 0-mers ID NO: 11; each start position is specified, the length of peptide is 9 Each peptide is a portion of SEQ Each peptide is a spectfied the lengt ofppidDs 1 amino acids, and the end position I O 1 ahsatpsto sNO: 11; each start position isfoeahptdeitesar poitonfor each peptide is thestr specified, the length of peptide is specified, the length of peptide is 10 poiinplsegt 10 amino acids, and the end amino acids, and the end position fort positionpluseight __J position for each peptide is the each peptide is the start position plus pq -s nei Score<-, start position plus nine. nine. _ eg cSubsequence F 2 7 RPSQrRVTH 10.0201 7 RPSqRRVTF 0.003 2 JSHRPDaO 8 RIRNTrR0.020 [37 ! VSVHtRPSQR 0 [ Tabl SVHTrPSQRR X.l2l Table XX-109P1D4v.5 4 HR0 B3501-9-mers LEach peptide is a portion of SEQ iID NO: 11; each start position is specified, the length of peptide is 9 Cterminal-Al-1O-mers Table XVIII-IO9P1D4v.5 amino acids, and the end position ach peptide is a portion of SEQ ID 137-9-mers for each peptide is the start N ; s io positions pluss eight Each peptide is a portion of SEQ ___poionluegh.specified, the length of peptide is 10 ID NO: 11; each start position is P-os [Subsequence Scramin acpide sn the endr position fors specified, the length of peptide is 9 eachRT peptide-R istesatpoiinpu amino acids, and the end position z][ PSR TF ooo:nine. for each peptide is the start e. Sb.. score poison H u _ 0_ih 0.050 4GVVHRS 5V~PDSR .0 LSubsequence Score 6 RPSQRR L0.011 1 PVSVHTRPS 0i15 L VHTRPSQRR 2._6 PVSVHTRPS 0.0100 I 1L K L JPQR I __3SV TRSQ 0.10 ____[_PVSvHTRPTDJ1.0030 0PSQRRVTF 0.00 F8 [ SVH 0.010 2~~VSVHTRPVSQhTRPT 0.000RSRR 0.0 [.I j TbRP QR L_ Table X-X-99PPvD4v.6 PVVHRP I0.010 Table XXI-11 09P1 ] ,LC'termial-A0201.-9-mars B7F -10HT-ers-B61-0mes; Eac VHTRPSQR [ 02 - - 1--.. Each peptide is a portion of SEQ ID N:Each peptide is a portion of SEQ ID NO: 13; each start position is IE12~.H.SyJRlTFH[ 19o NO: 11; each start position is specified, the length of peptide is 9 Specified, the length of peptide is 10 amino acids, and the nd position for Table AM-09PID4v.5 amino acids, and the end position for each peptide is the start position plus B7-10-mers each peptide is the start position plus' eight. I - - - - - - I i n .

onin e .~q e~ Each peptide is a portion of SEQ ID 1 o Se Score NO: 11; each start position is P7s Subsequence IScorej F I 3 SVH TRPTDS 0.00-77 specified, the length of peptide is 10 =f =-VPvHTRPS 120001 i1 amino acids, and the end position for I VV T.1.91 each peptide is the start positio.400I 0.5021 5 RT_11 0.0.00 1_ VPVvHTRPS 0.400 8q RSb QRVTFH or200) 4_ I RPsqrR 0.300 [ VHTRPTDSS .075 5 HTR~sQRRT 1.500 RTRPSqRRVTF 00.10 3 VSVtRtRK| PSQRrVTFHL 0SQR 0.050 Table e-9P1D4.6 LL~ H.~rk 9.99i 1 5_ _VHTpSQRV40.020j C'terminal-A0201-10-mers 8H 0. I47 SHjrPSQRR 1o.010 Each peptide is a portion of SEQ 2ID NO: 13; each start position is F.6_SV6rFQR 0.075.~TRSQ 0.00 ... _..... . . -.... ............. . specified, the length of peptideiis LVHTRpSQRRVa a.i0dJ n 10 amino acids, and the end 3 iVSVtRPSQR .position for each peptide is the 2 i00 Table XX-1 091 D4v.5 ID NO: 11; each startpsto strisiin lsni. E-~pciid the 2egt of petd is 9 . q. 0-q WO 2004/098515 PCT/US2004/013568 160 f~s.Subsequence ___Table XIV0131PID4v.6 Tble XVI1-1I09P1ID4v.6 VPVSvHTRPTterminal-A 1-9-mers erminal-A24-1 0-mers VHTRpTDSRT .0oo Each peptide is a portion of SEQ Each peptide is a portion of SEQ L__ V VH TDS J ID NO: 13; each start position is ID NO: 13; each start position is SVHTrPTDS 0.001 ET]f S~RPD 9.0 specified, the length of peptide is 9i specified, the length of peptide isI P SVhTRPTD 0.000 Tamino acids, and the end position 10 amino acids, and the end Sfor each pe tide is the start position for each peptide is the 2D VS hT J 9.001 position plu eight start position plu nine, specified, the length of peptide is 9j 'tria-1O-0mr amino acids, and the end position for each peptide is the start N:1;ec tr oiini position plus eight. ____ ______spcfetelntofppiei10Table X1II-1109PI 04v.6 Soe I oJSubseguencef Score aioais n h n oiinfr ,tria-79mr 5 HTRPTDSRTL0.007_nne 4 .~VHTRPTDSR [0.006_____IDN:1;ecstrpoions C3 SVHTRPTDS II.~04 a COLVSSVHTVPTHP 0.00001 Cter J V -A3 _DIL o . ~ ....... -. fo eac.petie.i.te.sar Table XIll-109P1D4v.6 I VHpTST 003,,:SHRT C terminal-A3-1 mers Each peptide is a portion of SEQ 1_P VHYrPTDL I ID NO: 13; each start position is Table XV-1 09P1 D4v.6 2 VSVHTRT specified, the length of peptide is terminal-A24-9-mers 10 amino acids, and the end Each peptide is a portion of SEQ position for each peptide is the sa NO: 13; each start position is start position plus nine. sable XIX-109P1 D4v.6 sSubsequence amino acids, and the end position reach peptide is the start sto ls Each peptide is a portion of SEQ L_ _ SVHrgTSR If.. ~ ~ E n.± ~ oiinplseh. ID NO: 13; each start position Is = LVSVHtPTDS :ITooj___ specified, the length of peptide is PVSVhTRPTD amino acids, and the end VHT7 1pIp EQ4 E [=HrT .0 Eachfor each peptide is the aonfS ID NO: 13; each1s 0.00arttpositi [minoaid] a theDT enTSubsequence Postio plus eight. L- ,_-PLVSVTRTDTRST . I V PVS0HTRPTL 69J TTable XX-P-109P1DD4vv6 .6 C mterminal-A' t mers Ar EEach peptide is a portion of SEQ ID NO: 13; each start position is DTable XVI-13 e 9PIaD4v.6 5VHTRPTD specified, the length of peptide is tCterminal-A24- -mers 9 2 F TTVI\IqS 0.008 amino acids, and the end nEach peptide is a portion of SEQ position for each peptide is the ID NO: 13; each start position is J_~ ~ ~ ~ ~ ~ ~~~psto plusar eigin lsnne al XX19I d. specified, the length of peptide is 9 _. ,]SCC' ter narinA17- 0010 mer [h7Subsequence Scoe amino acids, and the end sition50-9-er I VHTRPTDSR 0.004n for each peptide is the Each peptide is a portion of SEQ position plus ine. ID NO: 13; each start position is S tRPS 0.000 i scspecified, the length of peptide is =2 HTRPTD 10amino acids, and the endpositiontf S0 tDS L i for each peptide is the start ______TD 11.-1 L _ arpotion plus eight. [ P SHRT sSSubsequenc LEVH RPIDS_.00 PSf T .0 TaTabl XV1-109P1DD~v.6 CC' terminal-A24-9-mers --Each peptide is a portion of SEQ ~~~~~~~~~ID NO: 13; each start position is beXI-0PO4v6500, ~~~~~~specified, the length of peptide is 9 riaA2-0ms ~~~amino acids, and the end position _ah ~~~~~~~~~for each peptide is the startIDN:1;ecstrpoions ~~~~~~position plus eight al M0P ~. 1 Pos S~c 10 amPos Subsuenc e SeC em lB519mr IF- ilVHTRPTSHTRPTDSRT4 SVHTTL _JL SVHTPTD 01 VSVHTRLPTLVVHIPT 000o ahppiei h tr -AD NO:tio 13;s eac sarpsiioi WO 2004/098515 PCT/US2004/013568 161 [Pos fiSubsequence =Scorej Table VUII-1O9PI04v.6 HTRPTDS 0.300 _rmina-A--mers jt T 9D e Tn'narm_350--10-n-ers .10 Each peptide is a portion of SEQ ID NO: 13; each start position is Each peptide is a portion of SEQ 12 [VSVHTRPTb 110.050 specified, the length of peptide is 9: ID NO: 13; each start position is PVSVHTRPT t amino acids, and the end position specified, the length of peptide is 1 H ds for each peptide is the start 9 amino acids, and the end position plus eight. position for each peptide is the S Subsequencestart position plus eight STra S i Subseqce SShI 22 KCLLSGTY Each peptide is a portion of SEQ ID NO: 13; each start position is I 12. VVRVNTTNC i L NSDISSV 13.511 specified, the length of peptide is 91 10 amino acids, and the end sin MTNSI931 position for each peptide is the s3 tyartTNCH 1 , iton lus ine qHKLL oo17 YTNCHKCLL q.297 S DIVSV0RV .22 fi VPVvHTPT 2.00_ I Table IX-1O09P1 D4v.6 231CLLSGTYiF 11o.13 EOLUSVVRVN 630] _ 1[IIZL VYRPTDS fo1 I N' terminal-Al-i 0-mers 10 SSWRVNTT t1i 1SVHTrPTDSR Each peptide is a portion of SEQ 4 SIGFNSDISSV fK~~I VNTpO:R 13 0.W each start position is O ______________!0.01 specified, the length of peptide is 9 ISSWVRVNT 0.0831 f~7~f~vshTR TrD-fo7aoiT 10 amino acids, and the end 12 VVNT_'056 position for each peptide is the NCHKC ........str psition plus nine. STabl VIII-R9P1D4v.6 P OI071 V3VGFNSSS 0.0031 Each peptide is a portion of SEQ CLsYIF .20 ID NO: 13; each start position is 22 f 0 :10q001 specified, the length of peptide is 92 0i, am ino acids, and the end position a d n.the.end 1o s t for each peptide is the start 5 DiSSWR, g. H L 00 _position plus eight.nSISS , I SubsequenceSu e20 g ~ll 1L L S~gTIFA0.050i E ij 2LF FPo 7 . L .TV1SSVVR 0V025 6 SSR 0.20 8DVVRVNT 0020 IF LGFNSL SSV_ L7E-2 issvvRVrT J10 2=1[CHLS GT_ 161 NTTNCHKCL 1 0.0 5 .f ...........j.... G S I9 Table 0X-109P1DTablevX.-169P D4v.6 _____ 0N k C G 0.1 - terminal- m-A0201-10-mers - _13 peptide iso io of S Each peptide is a portion of SEQ ID IDj j NO: 13; each start position is .- A]0 specified, the length of peptide is 10 3 SSVVRVNTT .015.* -F--7F--1 amino acids, and the end position for ............. INoTio n C H p t e a ch p e p tid e is th e sta rt p o sitio n plus N poCLLS si.0131 s nnine. TVGFNSDIS 0.010 LSSco -~~ ~ 2 ,11- i G 1~6000 KCLLTTNqhKCL O I25u 22 K6,616Y 0.101 VRnTCIoo23- LLgTYIFA 15.68 FNS iSSVVR~ 0.00 8 TNVn0.010S 3 .FNsDISSV 6.568 _SDi7SvRvNTTNC .001 90L V0.00. 14 RVNTtNHKC 0.435 ._ _ ........ -- f_ __ _ t_ _ _ S V v T N .3 S FNDISSV jI0.oo1 j2 HKCLSGY 0.0II_________ Vs... IVNTNCHC tooo3 ff ~GFNSdISSV 03o,~ 048 J1 0.SVV vNTTNC 0TTf D F v 1.0. HKCLISGT... OSOI4 WO 2004/098515 PCT/US2004/013568 162 :.Table A-1 09P1 46 I-0PD4v.6 Table X11--I09PI D4v.6 N' termi"Innal-A0201-021110-mers . .. .. .. ..... t.......nN aI-A3- r 9-mersa- . N'A '" 9 'temrermsn....-......1 0-mers-3- 0-er Each peptide is a portion of SEQ ID Each peptide is a portion of SEQ Each peptide is a portion of SEQ NO: 13; each start position is ID NO: 13; each start position is ID NO: 13; each start position is specified, the length of peptide is 10 specified, the length of peptide is 9 specified the length of peptide is amino acids, and the end position for amino acids, and the end position 10 amino acids, and the end each peptide is the start position plusfoec Posh nep i ne . strpoiinlufreah peptide is the start position for each peptide is the nine. position plus eight. I start position plus nine. _______ Subsequence ScoreI Ps fence Score s _16 NT~HCL 0.297 1 I21 HCLGY 001_ FNdSSW 0.001 _NTNgHKCL_9 d 15: VNTTnGHKCL 02 37 1 0 VNTTnCHKCL 0.001 9LSVvRVNTT 0 0 I9~iS~RVTT[.10 II GNDIUS .01_2 HKCLISGTYI .01 19 FNCHKcLLSGT [ 0.1120.001 10 S rVN 8 DISSvVRVN 0.001 TNCHkCLLSG 0 F _ _____iy _ __ _ _1§s A- __ ____ j 000 . L4 LGFNSdISSVV [0020' _______ ___. {7 DIsVN 2 TVGFnSDISS 0.007 00 ____________ HKCLISGTYI_.[ 0003 10000 Table XIV-9PI D4.6 _____ ___ ____N'terminal-Al10O1-9mers [22 jKCLsGTYI O003j [3 RNTC 00 _____ _ ____........ .P.9.61 [[DSvVRVN 0000; ac J IF TNCHkCEE.G .... .. . NO: 1 start position is 07HKLL L0NKCLS0.0 17 TT~KCL 001 1j[TCHCLS____specified, the length of peptide is 9 12 V~TNH 001 [ 0 CKLST1 .0 amino acids, and the end position for !each peptide is the start position plus 5 FN S[ iSS VV-R [0.01 T ~ .... os.eight. 0 cSSVVrVNTTN T000 XII-109P1D4v.6 N' terminal-A3-9-mersuseq-6n~1D wre 1 M T-vGfNs'DIS; 0.00 OCU jF 11 RVNTTNCHK 6 .000 Each peptide is a portion of SEQ 771 ID NO: 13; each ID NO: 13; each start position is 13 RVNtTNCWKI000 specified, the length of peptide is 23 OLLSGTYlF 2 2 C10 amino acids, and the end post position for each peptide is the ah po.start position plus nine. 2 L 0 _ F Table AII-_1O9PI D4v.6 PsI_ N' terrn al-A3-9-mers _Subsequence Score . G.NS..SS. Each peptide is a portion of SEQ _K 23_o: FL~TYF 0.606 NTNHKL OOj ID NO: 13; each start position is 902020 CL TIO2 6 specified, the length of peptide is 9 1 ]VVtNHK13 1 SVVRVNTN 0.3 amino acids, and the end position FJDERNT _l J --11 NIT RVNTTNCH 2.0002 for each peptide is the start KCLLTTqiK [699 , . VVRVNTTNC 0..0I position plus eight. |SVVRvNT 1,030T s Sb , RVNTtNCHKC02 0.020 [.:E3 TTNHK9T9F 0 .0L,7[ _ F NSDKSSW SVV TTN [. VVRVnRVN 0.020 I .1 H II...QI D !q5P FNESW .... 8 .~ DSS V 0.000... MTVGFNSDI I I VRVNTTNCH 7O1TTNCHKCLL3; ec h 21 pstKCLLSG 22 [KCLLSGTYII 0.027 8 CkVT 00 VGFNSDIS10.000 6-1 NSDISSVVR 10.020 j 17 [TTNChKCLLS 0'DSV 0..000 I NI 0.00 VNTTNCHKC 0.0 F-1-6[ NTTN LI 0.015 1 3 VGFNsDISSV 0.002: 10 SSVRVNTT ,,0.0 _I [7YNSVR VNTN 0.-005- R9] IS~ NTTJ 0.0021 i 9 1. ISVRN .000 Dil VSVNRTNCH 00 F TI 0.004 1 CLSGT 0.001 CHKCLLSGTS flOf SVVRVNTT 1[L~ j2 HCST .0 ISVVN L 0.000 WO 2004/098515 PCT/US2004/013568 163 Table 1ble XV-9P1 D4v6 Table XVX9-1V9P1D4v.6 F TbeX-10P v.LN a'A4N' terminal-A24-9-mers N' eria-210es N'terminal-AI111-10-mers; Each peptide is a portion of Each peptide is a portion of SEQ Each peptide is a portion of SEQ ID SEQ ID NO: 13; each start ID NO: 13; each start position is NO: 13; each start position is position is specified, the length specified, the length of peptide is I specified, the length of peptide is 10 of peptide is 9 amino acids, and 10 amino acids, and the end amino acids, and the end position for the end position for each position for each peptide is the each peptide is the tart position plus peptide is the start position plus start position plus nine. nine.egt L PotSuhtegnc ence score 1, ~ Subequnce~f cor l[oslSubequnce Scre :iDISSvVRVNT I0.140: VRVNtTNCHK .0PQ] IWSY .750 12 _VRVnTTNCH I- 00201 0 22 KCLLsGTYlF 0.018 jio SSWRVNTTj 0.180 _ KCLISGTYI L7~1 CLSgTYIFA_(0.1 F4hbv 1 068K qTGnSSjoo; H NTTNcHKCLL 0.010 iLf~~~VI~4 6 NDsWR q0 _DI]LILV SVV7vNTTNC 0~lL'@S 00300 16 17TTNihKCL VNLSI 0.140 MTVNSDIS 0SDISRV If NSDiSSVVR 0.0061 ' 2 1 4 20 T 6 002 E24]ECGESDISTI 004jj()NH LS 01015 FSiSR002 D R]VNTTnCHKC KO [.111 SVRVNTCf 0.0030 GNDS,.IO ~ 1 V~TNH~.1 L. 1 TThKLSL.0 12IWNTN 010 8 _TNCHkCLLSG 0.010 L DSSVTT 7N SIVR 0.5 Tabl X91DNHcLSTv, .006 1 KLSTJ~1 al VI-0P ~. 6 N termina- s 0 L. 0 0LEach peptide is a portion ofS SEQ ID NO: 13; each startpoions 15ositin cifie theh ln gt is 1 21 pt HCISGTRTC 00 9 amino acids, andTth 8h n postion T 0for poiioeachc epid s h i TTNCHKCLLS 6 N.002 6 NTTNCHKCLetie 4.0orin00 E 1 _RNTNC[.00 - 50Gmnoacd, ndte n 3.7 TN000 .00 2_KCLLSGTYeKCLLSG 0 ~~~~~~~~~~~~Each peptide is a portion of ~ ~ i usqec cr. - NDSV O20 S1Q ID N 002 eachstart4J[ T~IDNO: f 6 13; eacVRVNhTsar Position is specified, the length 1 TTNCHKCLL I .0 0N off pepide Iisi99aminoid I, d 0 the end psi67on forK eac Eaf end p tinH C 4.000 i thi iD the 1 start position rN po peptide eight. ~ ~eigh. -,lOQ I2 TGNDS6 P0] LSVbseTuenel cor CP SubNquncHK 0 J5 NSTe - 0 100i HKL 6.000 9 10 i aSVVRVNTTNi 0.210a 14 eN d 17 __ 17 ISVVRTTdKLS 10 0.1801 16 NTTNCHKCL 4000RVN . [ 'DSS0V 000 F -i TNCL Ii 3 .000 11 VOvTTNCT 0 0 18 09TNCHKC _ 0.0 l2 TVFSDI .100 P2 1 MTVGFNDI 1/50NSD__SS___.100 1=0~~~~ ~~ VVRVNTTNC]07?QlI- - -,1 RVNTNCH petd 0.030tono Ei F-jVRNTN .0 = LSDISDSSVVFI\ 0.015Q i NCKCLS 010 cds n heedF TTCK Tabe XI- 091 D . table X l0P 1Div.6E N'N' terminal-A24-10-mers ~~~~~Each peptide is a portion of S unEQNi VJ SEQID NO: 13; each start positii position is ~ specified, the length of-j peptideCL is.00 of peptide is10 amino acids, and the endVNT 0.0 the end ~ position for each petd is theNTN j0.1' peptide is the ~~~~~~start position plus n ineV .00 -T[- 01 KCLCGTKC 0.6.000 16 .YNTTNL 0200 15NTNH VN0CHC , 4 00 -17 ,,JTSSVt-rVNTTN O.0IO 1711 TTNChKCLLS 0.I50 T ITTISI 5 1SVVRvNTTNC 1.55 IDIP E N5 3 ahsar oiini WO 2004/098515 PCT/US2004/013568 164 Table XVIIl-109P1 D4v.6 Table XIX-1 09P1D4v.6 Each peptide is a portion of SEQ N' terminal-B7-9-mers N'terminal-B7-1 0-mets ID NO: 13; each start position is Each peptide is a portion of SEQ Each peptide is a portion of SEQ specified, the length of peptide is ID NO: 13; each start position is ID NO: 13; each start position is 10 amino acids, and the end 1seiidthleghopeidisspecified, the length of peptide is position for each peptide is the ~specified, the length of peptide is 9 amino acids, and the end 10 amino acids, and the end position for each peptide is the position for each peptide is the E7-L§ sequence Score start position plus eight. start position plus nine, 22 _KCLLsGTY 2 ]Los tSubsequence JPScore 1 N cKce [ ]LLSGTY 020 F3 VRVNtTNCH( K . VNTTnCHKCL 11.000. 3iD7 LVGFNSDISS Jj0.020 20 CHKCILSGTY 20 T HKCab lSe 0.010 1 Table XX-109PD4v.6 9 ISSVvRVNTT 0.5001 NN' termeinral-B3501-9-mers _____ - 0.010_______1__[ SSVrVNTTN 0.500i 1Each peptide is a portion of SEQ _____ ID NO: 13; each start position is I6 NSDIsSWRV 0.3001 13 specified, te specified, the length of peptide is 91 0 nc amino acids, and the end posi for each peptide is the start L J startpositionplu esitionplus eight [.9 CHKcLLSGT Table XIX-IO9PID4v.6 . I.... bubsequence Scoree nce TVGnSDISS Ipi 00 Each peptide is a portion of SEQ 1T ID NO: 13; each start position is A-3 9LSGP§ lF 100L.LVGSl 010 specified, the length of peptide is TTNCHKLL 1.000 23 10 amino acids, and the end 17 I~TIF .10 position for each peptide is the 2 KCLLSGTYI_0.8001 TTNChK C0 startvpositio plus 50500 11 SVRvNTTNC 0.100 {s- _L Subsequence Score, F 10 SWVT 0.0 21 HKLGTI 000 [JCHKCLL4 .1 V TT 0.030 1 1 FNTTlcHKCL '4.000! 5 T FNSqD 0.40014 1GNdSV~000 ]L J SHV0NTT3 000 Liii J VNTtNCHKCL 0.5001 FND. HKLST0018 NCkL~svF.LSG 2001 12]L VGnNDISS[ VN JS s N LI] VNSDlsSV O.1 i ISVVJPI9 2 __________ KCLHksGTLSlF TNCkC LLSG 18 N.010: .2 nCHcLT G 0 5 NTNCHK _ 0.1001 1 TVGbleI 0.00i 7 1 092sVRV10.001 IFNSDSSV.VR 0 aiH 3 - N SDISSvVRVNT O.1I2 3Each peptide is a portion of SEQ iD NO:.1 c s -tr p ID NO: 15; each start position is 211 nSDpSS t l h f p0.0301 1 specified, the length of peptide is 9 SNSDsSVVRV S SSV- amino acids, and the end position o f3 eh i for each peptide is the start F 2.04 . , .11start position plus eight GFNSdSSVV 0.0-6261 i 14] [RVNtTNCHK 30:261 N' temia B3- 9 -merss~uec T cr D NO: 13; eac start poitoni 22 KCLLsGTYIF 3i0 6 F SISV qPs Sbeuec. cr SSVVrVNTTN 0.020 NCHKCLLSG 0 'j7011 CiCO N i o-[0IF60] N1 SSSLSPLLL .00075 1 , M -TV~fN~DIS T 13 VN SD 4 SSLSPLLLV 6.075 hC 0.02 . ... .VR N T 18 TNCHkCLLSG 0.010, Table XXI-1O09P1 D4v.6 1 SLLS .3 ~L5J NS~ SSV R 0010N' terminal-B33501-10-mers 0SS S L _ L .030 FS.SSVVRD 0.0ISV 7L C CSVL SVRVNT21 L00 RVTTCH 2" LLVVR WO 2004/098515 PCT/US2004/013568 165 Table V11l-109PID4v.7 Table IX-1 09P1 MY Each peptide is a portion of SEQ N'terminal-Al-9-mers N'terminal-A1-10-mers ID NO: 15; each start position is specified, the length of peptide is 9 Each peptide is a portion of SEQ Each peptide is a portion of SEQ 10aioacdadDh n ~~~0amino acids, and the end psto ID NO: 15; each start position is NO: 15; each start position is fortio each peptid pepsd the star specified, the length of peptide is 9 specified, the length of peptide is 10 psto o ahppiei h amino acids, and the end position amino acids, and the end position for I for each peptide is the start each peptide is the start position plus: EPo5K Subsequence Sco~re] position plus eight. nine4 [SLSPILLVSV 15.7 Subsequence o Subsequenc 6 rFLesSSSSL F20 LVSVVRVNT 0.025 I [ 0.003 I 17 13 10-1 S-SL PbJ 0015I 1 [ 2 -7 LFRVGfLUlSS [0( L F1 97 1 LSVVNi1. L SVVRVN 01LLLvSVVRV If 2. T-Y- 4Y~f~i C __ ..- q 5-Y1SL. 0.02 SSvsPLL 1.04 0.010 _S_ ___ LllSSsSSL 0.010 1 MFRVgFLIIS 0 ----------- 61 -1 FLIS SS .01 .I 9 if SSLSPL~IfV 0.545 EIL VGLll S SS-~ =- I.0 Tablee IX-109P1DDv.7 [7711000 TaleXIO9PD~v7 Li ifSSS ISPLLL 0f.139: N'7L1 I N'terminal-A0201-9-mers te rm .mer 9[Each peptide is a portion of SEQ1f ID NO: 15; each start position is 1N L.7 FRVGFLIIS 0.003 specified, the length of peptide is 91 0V77L §sSSSLS amino acids, and the end position - p-- for each peptide is the start 3 pFuLssS VS GELIISSSS I ~ pson plsegt I~SLP-0.003 LPos MFRVGFL Subse quencubsSoquencerecore _ 4--, VGFqiS 12 SSS LLLVSLVR 1V 13 FSSLPLLLVS l PLIISSSSSL 4.993 21 VSVVrVNTTN If N' terminal-Al -1 -mers 1 1 L1_j SFL~pSSSVS Each peptide is a portion of SEQ ID .. 1 ISLSLL ..... ..... s -oo I NO: 15; each start position is SPLLVSVVR specified, the length of peptide is 10 1.584 [ ... F IS 0-.0 amino acids, and the end position for'~ kL each peptide is the start position plus~j [ 7 I v , 0 LVVRVT 1.0 1D MXF v-g FL -0 .000F-L nine. FL6 F LSSSSSSS L ble.321 Table A I-1X09P9D4P.7 N 'F , ri n a1 90 N 'te rm in a l--9 -m e rs 005 Each peptide is a portion of SEQ I _____ ___NO 15 each_ ID NO: 15; each start position is ,SSSSISPLLL. ,specified, the length of peptide is [13 f ~pLLLVS I f. j LS V 0.070amino acids, and the end position for each peptide is the start ..... IVSVVR .. . 05 199.. ..... RV 0.024.... position plus eight. _ _ 10 S08 Sbsubsquence 19 LLVvVRVNT 0.0202 3 RVGfLlSSI 0.0031 PLLSV _090 1 LFLIISSS 0.007 [2 VSVVrVNTTN__F0-1 -5. [1-7 f MERVOFLI IF. 0.00i; ~i L V[.8 l[SSsSLSPL '0.015 F 17 _ PLEMvSWR7007 LIISSSSSL[ 0 I1 6.01V GFLlISSSS 0001 i 8 LLVs\VVRVN f0.0101 .-7 2 F J RVGF I IS 0.00070 LVSVVRVNT 0.1 20_1V )NT .1 SSSSSLSPI .000 f 9iLLVSVVRVN 10.013 3 RVGFMRgSSS 0S010 7 0Table X-109P1D4v.7 - IL ~~N' terminal-A0201-9 -mrs 16 SLVS 0.9 LlI7 USsSS-LS 0FE.00P5i P6 aminocids. and te e position0:1,= for-- !each-n peptide' is then tart E L S LL-,L !Epoitio plu eight- w WO 2004/098515 PCT/US2004/013568 166 Table Al1-109P1D4v.7 Table Xlll-109P1D4v.7 Each peptide is a portion of SEQ N'terminal-A3-9-mers L N'terminal-A3-10-mers ID NO: 15; each start position is Each peptide is a portion of SEQ Each peptide is a portion of SEQ specified, the length of pepide is IDN:1;ec tr amino acids, and the end psto ID O:15 eah tat osition is NO: 15; each start position is10 aisanthed specified, the length of peptide is 9i specified, the length of peptide is 10 position for each peptide is the amino I artposition plus nine. aioacids, and the end position amino acids, and the end position for, for each peptide is the start each peptide is the start position plus os Subsequence I r position plus eight. nine. osPLLIVSVVR 0.060 T T s L ELIIsSSSSL 1SSSLSPLLL ____0__ lRVGFIIISS 0.006 SSSSSLSPL 0]- .S .V. 004 Ffs ISSS S 0 [___ L__s§___ U.. 1.0-9-, '20-1 LVSVvRVNTT_ 0.002i7 I MFVGFL__~f7~6~ ~....~.5 GFLIiSSSSS 0.1 ir KSLIPL Tale IV-D09Iv.7. f 1[SSSLPL 0.003, Tal I-OPDV7F8 IISSsSSLSP 0.001 '21 termi VNTT a-0A002 Each peptide is a portion of SEQ FD ID NO: 15; each start position is it 2 ,.FRVGFLlS specified, the length of peptide is 9 amino acids, and the end position for for each peptide is the startpositionpl 5. .. GFLIIS_.i9557.2 position plus ei ht MFRVgFLIIS 0.000 I 9 ISsSSque nce OOI Fw Subsequence Score 1 SSSLsPLLLV .000 7L F SSS V 0.012 L SSSSsLSPLL 0.000 1 al SLS-1PISD450] SRVGFLIISS 0.012' 15 N'terminal-A3-10-mers LSP-ILVSVV E Each peptide is a portion of SEQ IDp e ptide D.063 ISSSsSLSP i poo o NO: 15; each start position is 7 LIISSSSL 10.006! 1 18 N LLLV5R;N Ie 0000 specified, the length of peptide is 10 _ _sMFRVGFL I 0.004 10 amino acids, and the end position for0 2 J FRS L IIS each peptide is the start position plus __I__ nine. 20 nSSS if o s j ~ b s q u n c ~ _ c o e' L I S S _ 0 0 1- 2 V S VVR VV NTHN J O .0 0 0 FL [f i SsL 7 0.90 f_14 SIS4SS S L I_ 1vTaL Table XVIX99P1 E___ -______ J___ 0.00211 SLSLL _J S i 0I N'terminal-A24-9-mers hEach pepide is a portion of SEQ 1ID NO: 15; each start position is 17 .6.... specified, the length of peptide is F_ _SSLSP .[9o amino acids, and the end position _for each peptide is the start 18 s.[S. position plus eigh LF oJL00 s Subsenqcuence scoScore LsVSVVFRVGF I0 .006 i L !!SSSSLSL 00 11PIL 0.006 jil 1 j LLVSVVRVN o1oo I_ _ MFVGLI 600 MFRVGFGFil 0.004~q sPLLL -i LSLSP kVS j[0W FT12 SSSLsPLL_1- 0.005 F~ IiSSSS 0.000 -7 SSSSLSPLLI 4.800 0VGFLIISSS SSSPL [4000-J LE j V3VVRPL TT 0 000 _j 8 SSsSSLSP[ 04SVSSSL 00 'ISSSSSLSPL Ho -6- 11__ ['sBC 0.003 __ _________ ______ _____ ____ -GFLIISSSS 1.050 f15 j1 LSPLILVSVV fr 0.003 Table XV-JL 09PID4v.7 L N' terminal-AII- -mers 3 ' RVGFLIss [ .240 19 LLVS VVVRVRNN '[0210 _I9Yfl 1 =5 iIL_______ If I ijMR~gFLIIS:f 0.000Fi~[ LSLLLVS\QJ0.8 ]LVFLiiSSSS GF!S 0 -M-O ~ 21 V!VRNT 16 000j~ V i WO 2004/098515 PCT/US2004/013568 167 [ Table )V-1 09P1 M Yv7 Table XVI 1-1 09PI D4v.7Eahppiesapo on fS Q E ::Each peptide is a portion of SEQ N'terinal-A24-9-mers N rmn l0m ID NO: 15; each start position EcEach peptide is a portion of SEQ specified, the length of peptide is ~~~0amino acids, and the end psto IID NO: 15; each start position is ID NO: 15; each start position is10aiocdsanthed specified, the length of peptide is 9 specified, the length of peptide is position for each peptide is the amino acids, and the end position 1amnacdndtendstart position plus nine. for each peptide is the start position for each peptide is the Pos Subsequenc position plus eight. start position plus nine. o Subsequence uence Score 21 VSVVRVNTT[0.180 ___ 4.0S01 18 LLLVSVVRV 0 17 0.01VVV :j5" 6 FLIlsSSSSL 4j. 00 13 SSLSPLLLV 0.50 3]L VSVVRV6 ECDIISSS 0 SSS 00SSSLsPLLLV 0.300 TL XLVS-9D Table XV-O9P14.7 N' terminal-B7-9-mers LSIVS 20 LVSVVRVT 0.140 . .. R...

00 lEach peptide is a portion of SEQ I ~ PLVV 0 ID NO: 15; each start position is F j[020 F ISSSSSLS 0.100 specified, the length of peptide is 9: I S 0.1501 10 2 US amino acids, and the end position L--- r ___ foi onde is the start pLed RVGFIIISSS str psitionS plus 1 nine. p pi

--

1L 9 1 L. p 1 87 L LLLVsVVRVN 0 ZIOI KZJ&4~SVVR f 0 .p~j I~os Susequece. Sore I __3jSSLSpLLLVS 0.0 Tal Vl191~.~16 SPLLLVSVV 4.000 4 VFUISSSS 0.020i LSSSLSPLLS 4.000 CVG~rilSSS 01 0 ~~~~~~~~~Each peptide is a portion of SEQ SLPLC 7 -- sssLs Fk9 ID NO: 15; each start position is I - 4 1S specified, the length of peptide is 10 S S F7 M0Fi. 10 amino acids, and the end 20 .N.7.... position for each peptide is the Spsi for each petiesh start position plus nine. I IL MF 0.0 FRVGfLIISS 0.002 Pos sbsp nce . Scre 13 SSLSPLLLV 0.300 GFLiSSSSS '[0.002 1F15 LSPLLLVSV 0 'T LLLVSVVRV -1__ _ __ _ SaLL 1 0.200 Table XX IF-N' teN'terra-naBB3501-9-m7:9 4Each peptide is a portion of SEQ 0ID NO: 15; each start position is S 0.750 specified, the length of peptide is 91 I17 T MFRVgFLIIS I700j 1 19 )[LVSVRN F0.020 amino acids, and the end position 0for each peptide is the start _10 [SSSSLPL f00 Iy 4FVLSSS 0401o E-0T.leIsXV~~RN 0.0 | ] ~SLU SS 0o 00Sbeqec -~ -LVS~RVNT §&N' tr]LalVSVVRV0-mr 1300SSLLV 100 12VL1VLJLN. VIVVT 0] 4S 12[ SLSPLLLVS KOZO LLL~sVVRVNi SVVRVNS 06 0" 12 SSS~PLLLV 0lO ~VGF3LllSSSS 0.0220 16T ' iSPVSW 0.1011 .18 LVSSSS 00 0 0 SSFUISSSSS5..020 T-71 l1-SsSSLS1F6SSSSS-LsPv 01 5SSS ILEllS C-IT~~O m sVVV S PLVS .44 -- [- _]SLL Table XIX-109P1D0v. N' terminal-B7-ers7 SLPL, Eachv petd is a:otonoFE _D2:15 eachRN stat osiio i speci,-Vfie, h ent of pid is.;E6 poLVSV ito orec2ppie h star poito pALusnie WO 2004/098515 PCT/US2004/013568 168 Tabble XX-1099P1Dv.7 Table XX-1 09P1 D4v.7] Table XXI-1 09P1 D4. 7[. TbeXl9P v8 N' terminal-B3501-9-mers N'terminal-B3501 -10-mers A0201-9-mers Each peptide is a portion of SEQ Each peptide is a portion of SEQ Each peptide is a portion of SEQ ID NO: 15; each start position is ID NO: 15; each start position is ID NO: 17; each start position is specified, the length of peptide is 9 specified, the length of peptide is specified, the length of peptide is 9 amino acids, and the end position 10 amino acids, and the end amino acids, and the end position for each peptide is the start position for each peptide is the for each peptide is the start position plus eight. start position plus nine. ; position plu eight. o Subseguence j To7 re Pos_ Subsequence Score S MFRVGFLI2 FRVG 19 LLVSRVN 00OI f8~~I~sSS~~1 KIVPV .3 4 SLSPLLLVS 2 FLI00S 0.0 I 0 20 VSVRVNT 0 8 IISSSSSLS IL KE QP 1.5 6_ FLJSSSSS I 000i_____ 5 GFLISSSS 0.0 0DN'1;ec tr oiini 1 PLLL -VSVV 0fl!qL.F 9 ISSSSSLSP 10.00 i Thle p is 0P if 7 LKETQP 0.000 N -mr sl -- A2-0e 17 0 S 0.0 Each peptide is a portion of SEQ [c p s p of SE 171KKITQP 1 004 ID NO: 17; each start position is TbeXI1P .0 2 [h legth oio specified, the length of peptide is Ne10 amino acids, and the end Position for each peptide is the NO 5 c t p t i p 0.01 start position 0Puu nn.n cF th l o p i v k TF E I 0.0 Sbeun S Subsequence ][ncee ~~~~~~~~~~10 amino acids, and the end PLKIVI~o IGKETi Eahppiei oto fS Qposition for each peptide is the____ _______ INO15ahstart pos ition i s I KEVPTV6 01 trposkitionpls i eifid thPlnghsf epid i ubsequence Score 1 _LKIVP 0008. K~VPVL.2 9 IISSSsSLSPL :500 ~ ~ .~[ TIgKE 007 ia11.,SSSLiSPLLj 5.00 1if14SFpKE 002 1]LSPLILVSVV_ 1.OO 600aprin fSQ I .L~~TQ .0 FL sSSSSLt 10 amino acids, and the end ~~~~~~~~~~~~position for each peptide is the E KIV 00 F j IGKEF1.41 21 VSVrVNTTN 0500 _____6_______ ___ _________start position plus nine. ____________________________ 13able SSLSpLLLVS 50 ] 6 LLVSVVR 0s 19_ LLVvVRVNT 0.20 7_S I-.L 501M 15_____ ii __ _ 1.000 8 Lpept TV [0a0porEach peptide is a portion of SEQ ID NO: 17; each start position is F. [ RVGFISS specified, the length of peptide is 12 i PLLLV N 10.001 QO 10 amino acids, and the end position for each peptide is the 192 0.500 start position plus nine 20 VSvRVTT 0.10 :,LK~iTQP 0,00 I P[Subsequence [cr 74 VGF~iISSS 0.100 9 GF KiSSSSSV . .06 LK(IV .9 L _ A1-9mers 1- MFRLVgFLUS [0.001 Z :GLeTVP oooKETQV 004 [97 Each peptide is a portion of SEQ ~ID NO: 17; each start position is RVGFIISS MW07.specified, the length of peptide is 9 amino acids, and the end position ~for each peptide is the start F--j-g-F v -v = F FlpI-K position plus eight. 1D~~q---LLVS~vRVNPo 7 01ubsequenceqenc Sor 7 LKKEiTVQPT O VGFIPGLKKF- 0010: Ul~~sSSSLS K01 [ LE fgnT 0 001 Lo L L TFfLKK OL PGlKKEITV 1:35 0-- -sVI' .2 WO 2004/098515 PCTIUS2004/013568 169 Tal O1110P1 D4v.8 Table XVII-109PID4v.8 Tab e rsl- Table XV-109P1 D4v.8 i A___24-10-mers j Each peptide is a portion of SEQ A1101-10mers . Eac .i o f ID NO: 17; each start position is Each peptide is a portion of SEQ SEQ ID NO: 17; each start specified, the length of peptide is 9 ID NO: 17; each start position is position is specified, the length amino acids, and the end position specified, the length of peptide is of peptide is 10 amino acids, for each peptide is the start 10 amino acids, and the end and the end position for each position plus eight. position for each peptide is the peptide is the start position plus :P:oel fI S~ubsequene K ~satpsto plus nie~nie Pos Pos ub sequen KKEITVQPT 0.001 [ f PLKET [ 7o J i IPGLkKETVy- [0.004 4.jIPGLkKEITV IF0.100 4 PGLKKElTV =0.000 E L61LLKKEITVQP 2 TFPgLKKEI 0.002 F K t T 0 L1._Ljj,.__IPGLKKE,- i .000 6 [GLKKeiTfVQP 0.~001 7Y LKK~iTVgPT' 0.014.. _STFpGLKKE .. 001 0KKTVQP Table XIll-109P1D4v.8 8 KKEltVQPTV_ 0 _ STFlpGLKK E 1 A3-10-mers 9F FKKEITTE 0.00 F UjElIT-QV _____63 Each peptide is a portion of SEQ ____________ 0,002 ID NO: 17; each start position is specified, the length of peptide is XI-91v 10 amino acids, and the end i7 I1 GLKkEITVQ 110001 - Table position for each peptide is the BT9-mers start position plus nine. Each a _ ___ Table XVI-109P1 D4v.8 pDN:1epd ist portion fs Pos Subsequence Score ] 24-9-mers I _____ ______ ____ secifed, the length of peptide i ILKKelTVQP 090O 6 GK~eTVP 00- Each peptide is a portion of SEQI 9 amino acids, and the end 3 [FIPGIKKEIT 0f 00156 ID NO: 17; each start position is Iposition for each peptide is the specified, the length of peptide is start position plus eight. ,fiII~ih~Ei~yfQ209 amino acids, and the end _ _ 1_L IpGLKKEI 0.004 position for each peptide is the f enceF Scoe 8 I KEtVQ vfo.0 start pKtoVsitiPoTnpluseight .. . ... E - 2.0001 TFIPgLKKEl 1 Subsequence 0 7 LKKEiTVQPT 0 000 8 jkTiWQPTv1 0.020 ______ 0000 ~IPGLKKEIT 0.1001 4 PGLKKEITV 002 f9 KEITvQPTVE 0. 00 5FPLK PG.kITQ9.0 JF, ,, -r1 Table XIV-1 09P1 D4v.8 _ EVqP 0.036] 6 LIKEITVQP - 0.001 Al 101-9mers _ jf G EITV 0.015 f[ LKKE [7 Each peptide is a portion of SEQ 1E__ ID NO: 17; each start position is I LI _ KEITVQP -10.0021 Tal XX19PID48 specified, the length of peptide is 9, 137-10-mers amino acids, and the end position for each peptide is the start Tabl peptid is ao nf8 position plus eight. -10-mers ID NO: 17; each start position is specified, the length of peptide is!1 Pos Subsequence Score Each peptide is a portion of 10 amino acids, and the end 8 KEITVQPTV 0.0031 SEQ ID NO: 17; each start position for each peptide is the FIPGLKEI 0002~ position is specified, the length Istar position plus nine. 2 FPLKKEl P0021...... . 5 GLKKEITVQs GLKKITVQ 0.001' and the end position for eachPo ifSbeune FZI 3 PGLKKEIT peptide is the sta TFIPGLKKE 006 - inIPGLkKEITV__I4.0' 00PGLKKE 0V IPgIKKEI 0 FO~2 o l LL I TFIPgLKKEI 11.880 100 KKEITVQPT f 0I00 - . L1 6- L E1 A F E 71101EIT -1 _ _j WO 2004/098515 PCT/US2004/013568 170 Table AM 09P1 D4v.8 Each peptide is a portion of SEQ Each peptide is a portion of SEQ 137-10-mars ID NO: 17; each start position is ID NO: 17; each start position is Each peptide is a portion of SEQ specified, the length of peptide is specified, the length of peptide is ID NO: 17; each start position is 9 amino acids, and the end 110 amino acids, and the end specified, the length of peptide is position for each peptide is the position for each peptide is the 10 amino acids, and the end startposition plus eight. __ I tart position plus nine. position for each peptide is the Pos Subsequen o.e Scor PFP] ;ubDSen Susqene s pKE3 IPGLKKEIT Pos FSubsequence I~oeI {TFGK E AO IPGLkKETV__f1.0001 6 L~eTQP_0OO F3 FIPGIKK EIT 0.1001 ____L KE Q VQ 4 _____V 8_______kIVQ 0.0401 -9 IKIQPV 0001, -it[PGLKKEITV 0.20 F IL 'TFIPgLKKEl .4 1PGLKkETVQ J0.001 1 61 i lKKEITVQP 0.0 f 6 GL~ ITQ - .03Q' -~~~~~ ~~ _____~---- f0067 KKEtVQPTV 1 0012 Table XX-1X09P1D4v.8-- 8 1 r.- 1 -W- -1.01 ID NO: 17;each startposition1i speifed the. .egt of petd

....

s... 9amino acids, and the endQ 830 KETVPT 0.040 B35 1- -mer WO 2004/098515 PCT/US2004/013568 171 Tables XXII - XLIX: Table XXII -109P1D4v.1 Table XXII -1 09P1 D4v. I Table XXIl -1 09P1 D4v.1 A1-9-mers AI-9-mers A1-9-mers Each peptide is a Each peptide is a Each peptide is a portion of SEQ ID NO: portion of SEQ ID NO: portion of SEQ ID NO: 3; each start position is 3; each start position is 3; each start position is specified, the length of specified, the length of specified, the length of peptide is 9 amino peptide is 9 amino peptide is 9 amino acids, and the end acids, and the end acids, and the end position for each position for each position for each peptide is the start peptide is the start peptide is the start position plus eight. position plus eight. position plus eight. _ _ _ _ _ _ _ I _ __I 911 EQTMKY 1 HTRPVGQV RETPNKL F59 TAMQFKLVY 22 F M3ENVLIGD 16 319 ETPNHKLLV 14 5701 FTHNEYNFY 278 EEDTGEIFT VESNQFLLE 1 807 TSDYVKILV 22 0 RIDREKLCA 1 514 SLDCRTGML 14 20 HGAQEKNY21 109 EVEVAILPD 16 542 AKDNGVPPL | 418 LETAAYLDY 1 IDNAPLFP 1HNEYNFYVP 14 495SGPNAKINY 63AVDPDVGIN 612ENDFTIDS 14 594VDPDYDN 4 DEPFRLR KAEDGGRVS 1 [985 SDPYSSD EKEDKYLFT 1 KPVFVP 1 VNDTLSE 2FOREKQESY 16 681SELVLES 37-01 LSENIPLNT KDVTDLGL 6 TDLFADQ 674 PPSNCSY NEIADVSS 7 Q DSLFSV 789 IEAPVIPN SSPTSDY 7 ALINELVR 14 168 VGINGVNY 897 DSDGNRTL 851 NSEWATPNP 3 NPSIDRY TGDVPLIRI 9 TLDLPLE 741 DLGLRV IRDEHCFY PLDNTFAC 931DSPDLARHY 9 11 LPDElFRLV 15 981 CSSSSSDPY 207 LDREEKDTY Table XXIII 109PID4v.1 PDEIFRLVK 141 QLLETAAY A0201-9-mers ENSAINSKY 4 YLDYESKE5 Each peptide is a portion P 75 _ fl1 of SEQ ID NO: 3; each 329ASDGGLMPA 24 LDYESTEY start position is 34 VTDVNDNVP 18 428SKEYAIKL specified, the length of _____________________________15 peptide is amino acids, 99 VDCGYPVT 9 LITVTDPDY and the end position for 221 VEDGGFQR 34 EKQESYFY each peptide is the start VIDTNDNHP 14AEDGGRSR position plus eight. 251 EIEVSIP S17 688SNPGTVF 23ATDADIGEN 1775TGMNAEVRY 1514 ILPDEIFRL 27 354 SIDIRYIVN 198 PYSVSDGY FLLETAYL 2 VDKDAHN 1KGDVPLIR 1 1 LLKDLLSL 39 FDHEFR IPENSAINS 1 GLMPAAMV 52_8DREKEKY EDTYVMKV 4 GMLTVKKL 567SVFTHNEY 7 278 IGENAKH LIGDLKDL 77DQETGNITL 1 11I IEPLDREE L~ 24tNIARRLFHL M 929 KPDSPDLAR 1

SLDCRIGML

WO 2004/098515 PCT/US2004/013568 172 Table XXI 1109P1D4v.1 Table XXIII 109P1D4v.1 1Table XXIII 109P1D4v.1 A0201-9-mers A0201-9-mers A0201-9-mers Each peptide is a portion Each peptide is a portion Each peptide is a portion of SEQ ID NO: 3; each of SEQ ID NO: 3; each of SEQ ID NO: 3; each start position is start position is start position is specified, the length of specified, the length of specified, the length of peptide is 9 amino acids, peptide is 9 amino acids, peptide is 9 amino acids, and the end position for and the end position for and the end position for each peptide is the start each peptide is the start each peptide is the start position plus eight. position plus eight. [I _ _ I I I [ 1 817 AVAGTITVV W41 54 GVPPLTSNV 20 369 VLSENIPLN 118 880 NLLLNFVTI 24 550 LTSNVTVFV 238 ALITVIDKD 1 64 KLVYKGDV 656SAKVTINVV 20 403 EIPFRLRPV 18 231 STAILQVSV 23 658 KVTINWVDV 2480 SPGIQLTKV 1 307 GLITIKEPL IVGGNRDL496 GPNAKNYL 8 375 PLNTKIALI 23 725 AIDQEGNI 20 609 ILDENDFT 539 TILAKDNGV TNATLINEL 617 TIDSQGVI 745GLHRVLVKA LINELERKS 6931 TVVFQVIAV 18 1YVKILAAV 826 VVIFIAVV 33 ITLMECDV 813 ILVAAAGT GTYFAVLL 1TLMEKDVT 18 38 VLIGIDLLKD 212 VLLACVVFH 1[7][RVLVKANDL 7 1VTDLGLHRV GAQEKNYTI ]GQPDSLFSV 18 816 AAVAGTITV 2 35 NAPLFPATV 62 LFSVVIVNL IFAVLLACV 162 VDPVGI TLINELVRK 18 76 RIEEDTGE 303 NATTGLIT 4 LVAAVAGTI 1 24 KIRFLEDI LVLASDGGL ITVVVVIFI 1 SAINSKYTL NTKALITV 9 9 LNSKHHI 18 301 HLNATTGLI 438AADAGPPL 19 958 SKHHIQEL DIRYNPV 1 503 YLLGPAPP 99 SVSDCYPV 360IVNPV1 DTV AKDNGVPPL YFAVLLA 17 YLFTILAKD 211 58 LPRHGVGL 9 LTTAMFKL 743 DLGLHRVLV 616 FTIDSTGV 881 GARIDEKL17 80 GTITVVVI 21 VAGTIIVVV 19 1131VINISIPEN 1~ 825 VVVIFTAV 81 LLLNFTIE 156 SKYTLEAAV1 999 TTFEVVSV VTLDLIDL DPDVGJNGV 1 50 SLIPNKSLT 9 QTMGYNWV 9 1 IKSQNFGL FLIEDINDN LLSGTYFA 8 VSIPENAPV 17 234 LQVSTDT LSGTYFAV TPNHKLLVL 17 270 QLHATADI 0 LLAVFHS 8 VLASDGGLM RLFHLNATT LPNKSLTT 8 368 LSENIPL 334LMPARAMVL 20 KLAGPRD 8 79 KIALIVTD 17 337ARAMVLVNV 20 FRLVKIRFL 8 GQLTVSA SMVLVNTDV 0 2 RLVKIRFLI 18 493ADSGPNAKI 37 DVNDNVPSI 2023DTYVMKVKV 1 56[HGTVG!OTV [I 39 YVNPVNDJT 2027 ADIGENAKl 18I]VLPSTIPGT 1 14281 STKEYAIKL O KHFSESNL HSLFSV lVN 71 WO 2004/098515 PCT/US2004/013568 173 Table XXIll 109P1D4v.1 Table XXIII 109PID4v.1 Table XXIII 109P1D4v.1 A0201-9-mers A02011-9-mers A0201-9-mers Each peptide is a portion Each peptide is a portion Each peptide is a portion of SEQ ID NO: 3; each of SEQ ID NO: 3; each of SEQ ID NO: 3; each start position is start position is start position is specified, the length of specified, the length of specified, the length of peptide is 9 amino acids, peptide is 9 amino acids, peptide is 9 amino acids, and the end position for and the end position for and the end position for each peptide is the start each peptide is the start each peptide is the start position plus eight. position plus eight. position plus eight. 764 SVVIVNLFV 882 LLNFVTIEE H96 1 HIIQELPLD1 795 TPNTE!ADV 934 DLARHY7SA 160NTFVACDSI1 819 AGTITYVVV 1008 HTRPVGQV SSSSDPYSV 15 965 ELPLDNTFV G41 DLLKDLNL 15 9 GYPVTTFEV 15 1006 SVHTRPVGI5 TTAMQKLV 1 44 LKDLNLSLI F2 ]DLLSGTYlF 146 ISIPENSA DLNLSLIN FAVLLAVV LPAAVDPDV 15 VYKTGVPL 14 42 DLLKDNLS INGVQNYEL CFYEVEVAI 49 LSLIPNKSL 181 SQNIFLDV EVAILEI 60AMQFKLVYK 12 QNIFGLDVI 1513 AILPDEIFR 14 67 YKTGDPLI 229 RSSTALQV LPDERLV 83 EIFTTGARI 23PVGTSVTQL 1518 LIEDINDNA 14 FYEVEAIL IHFSFSNLV PLFPAV1N 4 17 DEIFRVKI SFSNLSNI LFPATVINI 1 NISPENSA RAMVLVNVT SIPENSAIN 1 97KMPQLIVQK IPLNTKIAL 1 TLPAADPD 233AILQVSVTD 396 VTCFTDHE 15 NIFGLVIE 14 29 NLVSNARR 448QSAMLIKV EKDTYVMKV 291LVSNIARRL AMLFIKVKD TAILQSVT 30fFHLNATTGL 41MLFIKVKDE 1528VFKETEIEV 14 3 YAIKLLAAD 5 LLGPDAPPE 2 KETEEVSI AKLLAADA RTGMLTVV 310TIKEPLDRE 435KLLAAGK 1 GLITVIDPD KLLVLASDG 1 36LLAADAGKP VIRPNSFD ASDGGLMPA 5 KEDKYLFTI 643VKAEDGRV 15 335MPARAMVLV 553 NVTVFS VSRSSAKV 339AMVLVNVTD 87GTVGTVT 6 STNPG F 1 344NVTDVNDNV|1 5YGDNSAVTL 701NDTGMNAEV 1!32NPVNDTVVL 14 62NSAVTLSIL 77MNAEVRYSI 1538KDADHNGRV 14 5 SSAKVINV 7 TDLGLHRVL FSNQFLLET 6NDNKPVFIV 77IVNLFVNES 1545VFTQSEVTV 14 72DLFAIDQET 79NLFVNESVT 1543IQLTKyLSAM 14 74NDLGQEDSL 85KHSPKNLLL 1550KINYLLGPD 14 6 DSLFSVIV DSDGNVTL PDAPPEFSL 14 7FVNESVLTNA J i1ITLDLPIDLE 1!56DCRTGMLTV 1 I 01PTSDYMKIL i 96IDLPIDLEEQ IS 50[ILAKDNGVP 14 WO 2004/098515 PCT/US2004/013568 174 Table XXIII 109P1D4v.1 Table XXV- Table XXV A0201-9-mers 109P1 D4v.1-A3-9-mers 109P1 D4v.1-A3-9-mers Each peptide is a portion Each peptide is a Each peptide is a of SEQ ID NO: 3; each portion of SEQ ID NO: portion of SEQ ID NO: start position is 3; each start position is 3; each start position is specified, the length of specified, the length of specified, the length of peptide is 9 amino acids, peptide is 9 amino peptide is 9 amino and the end position for acids, and the end acids, and the end each peptide is the start position for each position for each position plus eight. peptide is the start peptide is the start position plus eight. position plus eight. 55211 SNVTVFVSI I L... I THNEYNFYV F7 70 TLINELVRK IVNPVNDTV 20 F67-8]1 SNCSYELVL KLDREKEDK 2 8RVLVKANDL 20 F86] LPSTNPGTV I 172 GVQNYELlK 24 I.2J VVIFITAW I 69011 NPGTVVFQV 4 RLPVFSNQ 20VVFHSQE 7061GMNAEVRYS 1 827 VIFITAVVR 24 [116] PDEIFRLVK f SIVGGTRD 39APHLKAAQK 24 VIETPEGDK | ig Iz-fI VNLFVNESV A422 AYLDYESTK23 KVKVEDGGF 773NESVTATL IVPPSNCSY 23 KVEDGGFPQ ER KE84A1 HLKAAQKN 23 TVTDKDADH 8121 KILVAAVAG 72FVACDSISK 23 FLLETAAYL 878 PKNLLLNFV VLLACVVFH 2AIKLLAADA 895 DVDSDGNRV 3AILQVSVTD NSGQLTK 948FQQPETPL 518RTGMLTK KYLFTILAK 19 2 IQELELDN 3GVIRNISF PLTSNVTVF 19 6 NVVDVNDNK TVGLITVTD 1 TableXXIV LVAAVAGTI DVNDNKPVF 1 109P1D4v.1 8RCRQAPH DVSSPTSDY 1 A0203-9 DLEEQTMG MIMMKKKKK 1 mers _9__F8-4 5SLTTAMQFK 21DLLSGTYIF 18 mo e65t LVYKTGDVP 238VLIGDLLKD 18 No Results F7 i ,8 Found. DVGINGVQN 21 6 AMQFKLVYK 18 298RLHLNATT RDREKLCA 18 Table XXV- 324 KLLVLADG 212 KDYVMKVK 1 109P1D4v.1-A3-9-mers KIALIT6TD 7SVTQLATD 1 Each peptide is a F-4 33 portion of SEQ ID NO: VVKLDREK GLMPARAMV1 3; each start position is 582NLRHGVG PLNQSAMLF 18 specified, the length of DVTDLGLHR 487KVSAMDADS peptide is 9 anmino__________________ acids, and the end LGLHRVLVK 540ILAKDNGVP position for each 812]KILVAAVAG 21 642YVKAEDGGR peptide is the start AVAGTITVV 645AEDGGRVSR position plus eight. 880 NLLLNFVT1 68KVTINDV RVSRSSSAK____ 191WVTTPTTFK 2168STNPGTVVF 18 65 01 RVSSSAK 18] KLLAADAGK____ 50 SLIPNKSLT 2064VVEQVAVD 18 AVLLAF113 AILPDEIFR QVIAVDNDT 1 NVLIGDLLK KMQLQK GLHRVLVKA 8 WO 2004/098515 PCT/US2004/013568 175 Table XXV- Table XXV 1 09P1 D4v.1-A3-9-mers 1 09P1 D4v.1 -A3-9-mers 802DVSSPTSDY Each peptide is a Each peptide is a 665DVNDNKPVF portion of SEQ ID NO: portion of SEQ ID NO: 3; each start position is 3; each start position is 241DTNDNHPVF specified, the length of specified, the length of F56 ) ENVLIGDLL ( 2 peptide is 9 amino peptide is 9 amino 109 EVEVAILPD acids, and the end acids, and the end position for each position for each 3 DVNDNVPSI peptide is the start peptide is the start [i02j)EVPVSVHTR F25 position plus eight. position plus eight. - ENSAINSKY 24 832 AVVRCRQAP 8 SVTDTNDNHIETPEGD Djf R1QE F81 F242 TNf HVl 16 3 511 NVSDIY2 RCRAP-L TNDN0PVFSNQFLL 24 71KKKKKHSPK 1827DIGENAKIH 1GVIRPNISF______ 1002 EVPVSVHTR 293 SNIARRLFH 16 VRYSVGG F 710 ERSV 2 106SVHTRPVGI 1834ATTGLITIK 16 FRLVKIR _____ F10-06]18 F3 04]16 1 181 FEIFRLVKIR 23 43 LLKDLNLSL13 VLVNVTDVN ETEIEVSP1 1 LIPNKSLTT 17 351 NVPSIDIRY PVGTSVTQL _ 95 KLCAGPRD 1 354 SIDIRYVN DVTD 12 LVKIRFLiE 1371SENIPLNTK 16ED 13)PLFPATVIN 1730IALITVTDK 1615[DINDNAPLF Ij AVDPDVGIN 449 SAMLFIKVK IKF 171EL1KSQNJF 11710 LLGPDAPPE 1[][ETLDYENI )N2 1 EEKDTYVMK 6GVPPLTSNV E16 IL F21-0]477-E61SPGI19 22 2 SIPENAPVG 17 608SILDENDDF 16F 2 QLHATDADI 171QE.SYTYVK 1ES Y 221 2 NLVSNIARR 17 700 AVDNDTGMN 16 [ 7 G N 2I ALITVTDKD YSIVGGNTR DVPLIRIEE 21 43 LLAADAGKP 17 73TLMEKCDVT 16DT QLTKVSAMD DLGLHRVLV 16LD F17]MF F624 E 7 F-64] 6 1 11 EALEI21 503YLLGPDAPP 175 LVKANDLGQ 16NV 61 77616717VG3NGV8N 21 64AVTLSILDE 1771SLFSVVIVN 16TPEGDKMP _____ 64 VIRPNISFD 17764SVIVNLFV EV1 71 EVRYSIVGG 17 10YVKILVAAV E F 2 75DLGQPDSLF 1794DLARHYKSA 1 ~JEETPNHKLL 21 765 IVNLFVN 1797PLDNTFVAC 1(36)DTVVLSENI 21 79NLFVNESVT 17TKEYAIKL ____ ATLINELVR.a 63TVVFQVIAV 2 81ILVAAVAGT 17 A26-9-mers 806PTSDYVKIL TITVVVVF 1 Each peptide is a D9GYPVTTF__ 1013 QVSNTF portion of SEQ ID NO: LVS IAR L 55KSLTTAMQF 16 3; each start position is F29V1] 20 specified, the length of 3 VVLSENIPL 73 PLIRIEEDT 1 peptide is 9 amino 391 DHNGRVTCF20 74 lRIEEDTG 6 acids, and the end 131 DINDAPLF position for each 523 KLDE2 peptide is the start 555TVFVSiDQ LIYQKELDR 1_ position plus eight. 895DVDSDGNRV WO 2004/098515 PCTIUS2004/013568 176 Table XXVI- Table XXVI- Table XXVI 109P1D4v.1 IO9P1D4v.1 IO9PID4v.1 A26-9-mers A26-9-mers A26-9-mers Each peptide is a Each peptide is a Each peptide is a portion of SEQ ID NO: portion of SEQ ID NO: portion of SEQ ID NO: 3; each start position is 3; each start position is 3; each start position is specified, the length of specified, the length of specified, the length of peptide is 9 amino peptide is 9 amino peptide is 9 amino acids, and the end acids, and the end acids, and th end position for each position for each position for each peptide is the start peptide is the start peptide is the start position plus eight. position plus eight. position plus eight. [ I [I _ _ I I__ 931 DSPDLARHY 20 w 18 277 DINK 15 83 EIFTTGARIIF 1 D LLSGTYIF 73-2-01 21 KVKVEDGGF 1 IM DEIFRLVK TI F M N R5 319 ETPNHKLLV 19 213DV K 17 F3631 PVNDTVVLS [6 326 LVLASDGGL 350 S3 533 EDKYLFTIL 372 ENIPLNTKI 17 F470 FVVSIPEN 1 715 IVGGNTRDL 431 FEYAIKLLAA 4 471 VTVSIPENN 7481RVLVKANDL 9578 YELR 17 549 pLTSNVTVF 15 765 VVIVNLFVN 587 GT 7 L5z SP H 809 DYVKILVAA 9 704 D17 [9II LITVTDPDYI 823 TVVIFIT755 DLG=QPDSLF 17 605]1 VTLSILDEN Fs 825 V VIFIT 822ITVVVVIFI 17 646 15 VTLDLPIDL 0 89-9] N 17 662 NWDVNDNK 1 r5iETPLNSKHH 5j~ TIAL F161 FFVPN 1 5 AVLLACVVF 16 Vl 16 7 E 33 EMPENVLIG F17 ] FHSG 6E 1 7-84] E E 3 LIGDLLKDL E7 E I 16 832 AVVRCRQAP 15 57 LTTAMQFKL 163 V16 860 E15 41 FATVINISIP 94] 15 142 TVINISIPE 529] E 886 E 15 168 VGINGVQNY 553 16 [9] I 253 EIEVSIPEN 604 I958 5 36 DIRYIVNPV61 DDTDQ 16rhi VGQST F1 403 EIPFRLRPV 658 6 458 DENDNAPVF 659 able XXVII-109P1D4 562 DQNDNSPVF 764 v. 1 v1-0702-9-mers FTHNEYNFY16 Each peptide is a 570I portion of SEQ ID NO: 666 STNPGTVVF j799 E 3; each start position is 694 VVFQVIAVD 1 specified, the length of ______________~~1peptide is 9 amino 72 DQETGNITL F1 820 W 16 acids, and the end 763 FSIVNLF16 position for each TITVVFpeptide is the start 824 VWIFITA 99 TEPVV 1 S890-] F TK VD 8211 8F76Ea petde oi ight. F8porti ofq SEQ ID NO: 3;1 each startposition2is WO 2004/098515 PCT/US2004/013568 177 Table XXVil-1 09P1D4 Table XXVII-109P1D4 Table XXVII-1 09P1 D4 v.1 -B0702-9-mers v.1-B 0702-9-mers v.1-B0702-9-mers Each peptide is a Each peptide is a Each peptide is a portion of SEQ ID NO: portion of SEQ ID NO: portion of SEQ ID NO: 3; each start position is 3; each start position is 3; each start position is specified, the length of specified, the length of specified, the length of peptide is 9 amino peptide is 9 amino peptide is 9 amino acids, and the end acids, and the end acids, and the end position for each position for each position for each peptide is the start peptide is the start peptide is the start position plus eight. position plus eight. position plus eight. 362NPVNDTVVL 262 APVGTSVTQ ]YGDNSAVTL 136 APLFPATVI AADAGKPPL 16 678 SNCSYELVL 13 320 TPNHKLLVL 23 493 FADSGPNAK 40 742 TDLGLHRVL g 374 IPLNTKIAL 22 06 GPDAPPEFS 1773 NESVTNATL 1 4 RPVFSNQFL F542 AKDNGVPPL 16 806 PTSDYVKIL 1 F7]PPSNCSYEL 22 858 NPENRQMIM 1 87 AVAGTITVV 13 7921 APVTPNTE 22 875 KHSPKNLLL 839APHLKAAQK f PPLNQSAML 2 897 DSDGNRVTL 899DGNRVTLDL 3 4961GPNAKINYL LPIDLEEQT KSASPQPAF IPFRLRPVF 20TPLNSKHHI 951 QPETPLNSK 131 52 IPNKSLTTA REEMPENVL HHIQELPL I LPVDPDV 477 ENNSPGQL 1 PENAPVGT PDAPPEFSL 15 Table XXVIl-109P1D4 I -IIMPARAMVLV197 IVGGNTRDL 1 mrs APVFTQSFV 9 FQIQPETPL Each peptide is a 4-]F4f portion of SEQ ID NO: QPDSLFSVV 19 11 RPVGQVSN 15 3; each start position is LPDEFRLV 1 IPRDEHCFY specified, the length of _________________peptide is 9 amino FPQRSSTAI INSKYTLPA acids, and the end 35 VPSIDIRYI PQRSSTAIL 14 position for each 44317 peptide is the start KPPLNQSAM REETPNHKL 14 position plus eight. 47 lPENNSPGI 8 0 APPEFSLDC 1 480SPGQLTKV KPVFIVPPS GPNAKINYL 548PPLTSNVTV KCDVTDLGL LLKDLNLSL 27 68LPSTNPGTV 1LFSWIVNL 4TPNHKLLVL 2 NPGTVVFQV 8741KKHSPKNLL 14 FKVKDEND 2 05 SPTSDYVKI SGTYFAVL SLDCRTGML 87 SPKNLLLNF 18 49 LSLIPNKSL 13 GAQEKNYT 26 929KPDSPDLAR VYKTGDVPL 24 HPVFKETE 96LPLDNTFVA 18 GARIDREKL 13 121STKEYAIKL 24 DPDVGINGV 7 EDINDNAPL 13 SPKNLLLNF 24 246 HPVFKETE AAVDPDVG FRLVKIRFL 547VPPLTSNVT 79 KSQNIFGL 13 216 VMKVKVEDG23 596DPDYGDNSA TPEGDKMPQ 375 PLNTKAL 7 TPNTEIADV 7 PVGTSVTQL EDKYLFTIL 2 1TPNPENRQM 171l [ EDKYLFTIL 11153LPRHGTVGL$L~ WO 2004/098515 PCT/US2004/013568 178 Table XXVIII-109P1D4 Table XXVII-109P1D4 Table XXVIIl-109P1D4 v.1-B08-9-mers v.1 -B08-9-mers v.1-B08-9-mers Each peptide is a Each peptide is a Each peptide is a portion of SEQ ID NO: portion of SEQ ID NO: portion of SEQ ID NO: 3; each start position is 3; each start position is 3; each start position is specified, the length of specified, the length of specified, the length of peptide is 9 amino peptide is 9 amino peptide is 9 amino acids, and the end acids, and the end acids, and the end position for each position for each position for each peptide is the start peptide is the start peptide is the start position plus eight. position plus eight. position plus eight. 41 GDLLKDLNL 22 24 KIRFLIEDI 1248 VFKETEIEV 14 66 vYKTGDVPL KVKVEDGGF 17 2 NAKIHFSFS 14 294 NIARRLFHL 2307 GLITIKEPL 283KHFSFSNL 955 PLNSKHHII 22 362 NPVNDTVVL 1308 LITIKEPL1D 88 GARIDREKL R 409 RPVFSNQFL 1352 VPSIDIRYI 14 36MEKCDVTDL 21 426 YESTKEYAil 17 354 SIDIRYiVN 14 4 RVLVKANDL PPSNCSYEL 403 EIPFRLRPV14 [86MMKKKKKKK 21 89APHLKAAQK ftj48AADAGKPPL 1 [87MKKKKKKKK f~J[06SVHTRPVGI 749 NAKINYLLG 1 KKKKKKKKH SAINSKYTL TILAKDNGV IIKKKKKKKHS 21 161YELIKSQNI ia 72APVTPNTEl 1 (]KKKHSPKNL 21 271PQRSSTAIL 11188SDYVKILVA 1 (7]KHSPKNLLL 21 30!TIKEPLDRE LI88NPENRQMIM 1 IDREKLCAG EPLDREETP 16 NLLLNFVT 14 31PEGDKMPQL PFRLRPVFS 8 SKHHIQEL 4 [AQKNKQNSE 20 44IPPLNQSAMLWe 7]KKKKKKHSP 20 633 REKQESYTF Table XXIX-109P1D4 ]KKKKKHSPK 2KAAQKNKQN v.1-B1510-9-mers TFKPDSPDL LIGDLLKDL Each peptide is a F9 ______ 2______]___H_ portion of SEQ ID NO: FLLETAAYL DEIFRLVKI15 3; each start position is F631 REKESY 1 178 LIKSQNIFG15 specified, the length of [78-][EVKTA_ peptide is 9 amino E3L9V1R DHNGRVTCF acids, and the end ]ILPDEIFRL AIKLLAADA 15 position for each 122]LVKIRFLIE 18 541 LAKDNGVPP15 peptide is the start F-F805H position plus eight. 3LMPARAMVL 1885SPTSDYVKI 1 374 PLNTKIAL 33 RCRQAPH KHSPKN LLL 41MLFIKVKDE 18 864MIMMKKKK 15 FHLNATTGL 52 LDREKEDKY 18 LIPNKSLTT 14 96 HHIQELPL [3]REKEDKYLF I 11 IFRLVKIRF 391DHNGRVTCF 656SAKVTINVV AINSKYTLP ILPDEFRL 16 666VNDNKPVF INGVQNYEL IKSQNIFGL 7TLMEKCDVT 1817ELIKSQNIF 14[iIVGGNTRDL[I 4HLKAAQKNK LIVQKELDR TDLGLHRVL 4KLVYKTGDV 203 KELREE 897 DSDGNRVTL ]VPLIRIEED 6FPQRSSTA 14 1LVSNARRL WO 2004/098515 PCT/US2004/013568 179 Table XXIX-109P1D4 Table XXIX-109P1D4 Table XXX v.1-B1i510-9-mers v.1-B151 0-9-mers 109P1 D4v.1 Each peptide is a Each peptide is a B2705-9-mers portion of SEQ ID NO: portion of SEQ ID NO: Each peptide is a 3; each start position is 3; each start position is portion of SEQ ID NO: specified, the length of specified, the length of 3; each start position is peptide is 9 amino peptide is 9 amino specified, the length of acids, and the end acids, and the end peptide is 9 amino position for each position for each acids, and the end peptide is the start peptide is the start position for each peptide position plus eight. position plus eight. is the start position plus S ] FLFIeight. 1400 TDHEIPFRL GLITIKEPL 762LFSVVIVNL REETPNHKL 12 394 GRVTCFTDH I 317 REEMPENVL 1 22 NHKLLVLAS 1DREEDKYL 2 104 EHCFYEVEV 1334 LMPARAMVL 12 8 NRQMiMMKK 24 120]FRLVKIRFL 1404 IPFRLRPVF 12 JLRPVFSNQF [3( 170INGVQNYEL 477 ENNSPGQL IRPNISFDR 318 EETPNHKLL GPNAKINYL iDREETNHK 3 NPVNDTVVL 497 PNAKINYLL VRCRQAPHL2 374 IPLNTKIAL GMLTVVKKL GDLLKDLNL21 4 DHEPFRLR 9 DREKEDKYL DREKLCAGI 5 PDAPPEFSL THNEYNFYV 12 F KMPQLIVQK 20 5YGDNSAVTL ~155YNFYVPENL 1263REKQESYTF 20 6TNATLINEL NSAVTLSIL NRVTLDLPI 20 TFKPDSPDL 665 DVNDNKPVF 47 LNLSLIPNK [ 1GTYIFAVLL 3676 PPSNCSYEL 12 304 ATTGLITIK 1 66VYKTGDVPL SNCSYELVL 52 GMLTKKL 19 FYEVEVAIL NDLGQPDSL PRHGTVGLI 19 13PEGDKMPQL 1384KKHSPKNLL 1263 GVIRPNISF 19 245 NHPVFKETE13 903 VTLDLPIDL 12RVLVKANDL 19 320 TPNHKLLVL 948FQQPETPL RIEEDTGE 18 429 TKEYAIKLL SKHHIQEL ELIKSQNIF 18 AADAGKPPL 07 VHTRPVGlQ RRLFHLNAT 1 AKDNGVPPL REETPNHKL 81 5 LPRGTVGL GPNAKINYL 18 688 STNPGTF Table XXX- 5351 LFTILAK 72 DQETGNITL 13 109P1D4v.1- GQVSNTTF 18 LHRVLVKAN 1 B2705-9-mers GTYFAVLL 17 F7-]Each peptide is a ___3 ________ 773NESVTNATL 13 portion of SEQ ID NO:REEMPENVL 806 PTSDYVKIL 13 3; each start position is KSLTTAMQF 17 SGT_____FAVL_ specified, the length of ILPDEIFRL 1 F-5- GTIFVL 1 peptide is 9 amino__________ FHSGAQEKN 2 acids, and the end IFRLViRF 17 35Lposition for each peptide 290 NLVSNIARR 17 GAR1DREKL 1 is the start position plus 307]GLITIKEPL 17 88 AISKL ITIKEPLDR 17 284 IHFSFSNLV FLKR R NV WO 2004/098515 PCT/US2004/013568 180 Table XXX- Table XXX- Table XXX 109P1D4v.1- 109P1D4v.1- 109PID4v.1 B2705-9-mers [ B2705-9-mers B2705-9-mers Each peptide is a Each peptide is a Each peptide is a portion of SEQ ID NO: portion of SEQ ID NO: portion of SEQ ID NO: 3; each start position is 3; each start position is 3; each start position is specified, the length of specified, the length of specified, the length of peptide is 9 amino peptide is 9 amino peptide is 9 amino acids, and the end acids, and the end acids, and the end position for each peptide position for each peptide position for each peptide is the start position plus is the start position plus is the start position plus eight. eight. eight. IPFRLRPVF 17 835RCRQAPHLK 16 141611 FLLETAAYL 15 409 RPVFSNQFL 39APHLKAAQK [AYLDYESTK 1H 479NSPGQLTK 1860 ENRQMIMMK 16 [-Jl STKEYAIKL 151 51 RTGMLTK RQMIMMKKK 4381 AADAGKPPL 1151 530 REKEDKYLF 17 8667MMKKKKKKK 16 445 PLNQSAMLF 15 645AEDGGRVSR MKKKKKKKK 4 SAMLFKVK 15 64 GRVSRSSSA 868KKKKKKKKH 1 9 PNAKINYLL 15 [0RVSRSSSAK 11181KKKKKHSPK 1859TGMLTVVKK 1 74 HRVLVKAND KHSPKNLLL 16 VVKKLDREK 15 LFSVVVNL KSASPQPAF 5 AKDNGVPPL 7TLINELVRK 1[09JTRPVGIQVS L157FYVPENLPR 1 F8 IMMKKKKKK 17 LLSGTYF 5 662NVVDVNDNK 94 FQQETPL AQEKNYTIR 15 6 STNPGTF 15 9 QELPLDNTF LSLIPNKSL 727 DQETGNITL SAVLLACF 82GEFTTGAR 728 QETGNITLM 5 NVLIGDLLK GARIDREKL 744LGLHRVLVK 1 IRFLIEDIN 16 1 VAILPDEF NDLGQPDSL 1 52SAINSKYTL 113] AILPDEFR 551DLGQPDSLF 17 IKSQNIFGL EIFRLVKIR ATLINELVR 1 PQLIVQKEL PENSAINSK 15 820 GTITVVVVI 1 2 REEKDTYVM VGINGVQNY 5863 QMIMMKKKK15 221VEDGGFPQR 1 201 LIVQKELR 73]KKKHSPKNL 276ADIGENAKI 16DREEKDTYV 5]KKHSPKNLL 2 KHFSFSNL PVGTSVTQL SPKNLLLNF 337ARAMVLVNV SNLVSNIAR DDVDSDGNR 5 350 DNVPSDIR 96ARRLFHLNA 1 F2 DKPDSPDLAR [1: 38 IALITVTDK GGLMPARAM 15 ARHYKSASP 4 KLLAADAGK VVLSENIPL 58SKHHQEL 517CRTGMLTVV 372 ENIPLNTKI DCGYPVTTF 7 YNFYVPENL 16ILNTKIAL VFHSGAQEK 713YSVGGNTR DHNGRVTCF 15 GAQEKNYT 74 TDLGLHRVL FTDHEPFR KNYTIREEM 7 TNATLINEL FRLRPVFSN 30 IREEMPENV 821VIFITAVVR [L140PVFSNQFLL LI[5[PENVLIGDL ~ WO 2004/098515 PCT/US2004/013568 181 Table XXX- Table XXX- Table XXX 109P1D4v.1- 109P1D4v.1- 109PID4v.1 B2705-9-mers B2705-9-mers B2705-9-mers Each peptide is a Each peptide is a Each peptide is a portion of SEQ ID NO: portion of SEQ ID NO: portion of SEQ ID NO: 3; each start position is 3; each start position is 3; each start position is specified, the length of specified, the length of specified, the length of peptide is 9 amino peptide is 9 amino peptide is 9 amino acids, and the end acids, and the end acids, and the end position for each peptide position for each peptide position for each peptide is the start position plus is the start position plus is the start position plus eight. eight. eight. 43 LLKDLNLSL 14 763 FSVVIVNLF 14 492 DADSGPNAK 13 57MLTTAMQFKL 804SSPTSDYVK 507PDAPPEFSL 1 60AMQFKLVYK CRQAPHLKA 4 533 EDKYLFTIL 13 66 VYKTGDVPL HLKAAQKNK DQNDNSPVF 1 68 KTGDVPLIR 14IR[MIMMKKKKK 14 569 VFTHNEYNF 13 1271 FRLVKIRFLI 14 897 DSDGNRVTL fY41 58 YVPENLPRH 13 5301 EDINDNAPL V 903 VTLDLPIDL 14 583LPRHGTVGL 13 FI 1APLFPATVl NWVTTPTTF 587 GTVGLITVT 13 D170! INGVQNYEL 951 QPETPLNSK 4 FDREKQESY 13 172GVQNYELIK PETPLNSKH DREKQESYT 1KDTYVMKVK 1SGTYFAVL SRSSSAKVT [IIKVKVEDGGF 1136 ENVLIGDLL 13631RSSSAKVTI11 ! 2801ENAKHFSF TAMQFKLVY 3 VNDNKPVF 13 SLVSNIARRL FTTGARIDR 3 IVPPSNCSY 13 FHLNATTGL TGARIDREK PPSNCSYEL M13 101TPNHKLLVL jj89 ARIDREKLC 13 !]IAVDNDTGM fY3 326LVLASDGGL 94 EKLCAGIPR 3 175IVGGNTRDL 13 330SDGGLMPAR GPREHF 3 TRDLFAIDQ 13 371SENIPLNTK 14 FYEVEVAIL 13 TGNITLMEK 400 TDHEPFRL 46 ISIPENSA 3 MEKCDVTDL 13 427 ESTKEYAIK ENSAINSKY NESVTNATL 13 443KPPLNQSAM IETPEGDKM 3 APVTPNTE 13 444PPLNQSAML 14PEGDKMPQL 3 TITVVIF 483IQLTKVSAM 275 DADIGENAK 854 WATPNPENR13 493 ADSGPNAK IGENAKHF NFVTIEETK 13 522LTVVKKLDR LDREETPNH 3 WVTTPTTFK KLDREKEDK LMPARAMVL 3 TFKPDSPDL 1 5 PLTSNVTVF 14NVPSIDIRY PDSPDLARH 5 YGDNSAVTL NPVNDTVVL HHIQELPL 13 608 SILDENDF QFLLETY 13 FVACDSISK 618 DSQTGVIR LDYESTKEY EVPVSVHTR 6 PNISFDREK TKEYAIKLL 3 711VRYSIVGGN ]DENDNAPVF Table XXXI-1 09P1 D4v.1 KCDVTDLGL 4 ENNSPGQL B2709-9-mers WO 2004/098515 PCT/US2004/013568 182 Each peptide is a Table XXXI-109P1D4v.1 Table XXXI-1 09P1 D4v.1 portion of SEQ ID NO: B2709-9-mers B2709-9-mers specified, the length of Each peptide is a Each peptide is a peptide is 9 amino portion of SEQ ID NO: portion of SEQ ID NO: acids, and th end 3; each start position is 3; each start position is position for each peptide specified, the length of specified, the length of is the start position piusd, peptide is 9 amino peptide is 9 amino eight. acids, and the end acids, and the end position for each peptide position for each peptide is the start position plus is the start position plus 20 FRLVIRFL 22 eight. eight. 834 VRCRQAPHL 337ARAMVLVNV 76 RIEEDTGE1 APLFPATVI 1 IREEMPENV 102 RDEHCFYEV 13 152 SAINSKYTL 1 529 DREKEDKYL 250 KETEIEVSI INGVQNYEL 1 901 NRVTLDLPI 283 KIHFSFSNL 13 193PEGDKMPQL 408 LRPVFSNQF LVSNIARRL GDKMPQLIV 1 51 CRTGMLTVV g ARRLFHLNA F199 PQLIVQKEL 12 584 PRHGTVGLI NPVNDTVVL 228 QRSSTAILQ 1 786 VRKSTEAPV V3V681 WLSENIPL 1263 PVGTSVTQL -2j DREKLCAGI IPLNTKIAL 13 284 IHFSFSNLV 12 DREEKDTYV FRLRPVFSN FHLNATTGL 1 GTYFAVLL 17 PVFSNQFLL 318EETPNHKLL 12 41 GDLLKDLNL FLLETAAYL [2 [[LVLASDGGL 1 748RVLVKANDL GPNAKINYL 1 333GLMPARAMV 2RRLFHLNAT 1652AKDNGVPPL 1340TDHEIPFRL 12 GMLTVKKL GVPPLTSNV 1 IPFRLRPVF GLITIKEPL YNFYVPENL 3 438AAAGKPPL 12 RPVFSNQFL REKQESYTF 13 444PPLNQSAML 6GRVSRSSSA 15 68KVTINVVDV 13 47ENNSPGQL 12 711VRYSIVGGN 5 GNTRDLFAI 3 IQLTKVSAM 3REEMPENVL 14 78KCDVTDLGL 1347PNAKINYLL 1 55KSLTTAMQF 87 KHSPKNL YGDNSAVTL 12 88GARIDREKL KKHSPKNLL GVIRPNISF 21RLVKIRFLI 14 TFKPDSPDL 625IRPNISFDR IRLIEDIN DLLSGTYlF SRSSSAKVT 1 2REEKTYVM W SGTYFAVL SNCSYELVL 2 229RSSTAILQV AVLLACF MEKCDVTDL 12 317 REETPNHKL ]GAQEKNYT TDLGLHRVL 332GGLMPARAM 14ENVLIGDLL 12 HRVLVKAND 7IRYVNPVN 149LSLIPNKSL 1274NDLGQPDSL 12 4GRVTCFTDH 167YKTGDVPLI 2170DSLFSVIV 12 5REKEDKYLF 75IRIEEDTGE 1272LFSVIVNL 12 3RSSSAKVT ARIDREKLC SPTSDYVKI GTITVVVV GPRDEHCF 1 AGTITVVVV 1 [6 KHSPKNLLL 5] 14ILPDEFRL 2VTLDLPIDL 12 KNYTIREEM EDINDNAPL KSASPQPAF 12 WO 2004/098515 PCT/US2004/013568 183 Table XXXI-1 09P1 D4v. 1 Table XXXI-1 09P1 D4v.1 Table XXXII-109P1D04 B2709-9-mers B2709-9-mers v.1-B4402-9-mers Each peptide is a Each peptide is a Each peptide is a portion of SEQ ID NO: portion of SEQ ID NO: portion of SEQ ID NO: 3; each start position is 3; each start position is 3; each start position is specified, the length of specified, the length of specified, the length of peptide is 9 amino peptide is 9 amino peptide is 9 amino acids, and the end acids, and the end acids, and the end position for each peptide position for each peptide position for each is the start position plus is the start position plus peptide is the start eight. eight, position plus eight. 960 HHIlQELPL H [75?] GQPDSLFSV P [fj PENVLIGDL [ 43FLLKDLNLSL 1 1[ 763 FSVVIVNLF 11 317 REETPNHKL 23 57 LTTAMQFKL j[ 80611 PTSDYVKIL 7 NESVTNATL 2 64KLVYKTGDV H 1821 [lTITVVVVIF REEMPENVL 66 VYKTGDVPL Ij1 [822jFITVVVVIFI 1 PEGDKMPQL 83 EIFTTGARI 1 [836 2CRQAPHLKA 4 YESTKEYAI 2 CFYEVEVA8 NRQMIMMKK KEDKYLFT 2 107 FYEVEVAIL 8 NLLLNFVTI IEEDTGEF 21 14611 ISIPENSAI DVDSDGNRV1 KETEIEVSI 2 162] VDDVGI DSDGNRVTL1 LETAAYLDY 2 YELKSQNI DGNRVTLDL 530 REKEDKYLF 21 1 IKSQNIFGL 3 ARHYKSASP 3 REKQESYTF 2 [IETPEGDKM 4 ASPQPAFQl 1 MEKCDVTDL i 213]DTYVMKVKV FQQPETPL LEEQTMGKY (27[PQRSSTAIL j6i 98SKHHllQEL 1117 YELIKSQNI 19 3201TPNHKLLVL QELPLDNTF 402 HEPFRLRP 18 334LMPARAMVL SSSSDPYSV AVLLAVVF 7 340MVLVNVTDV GYPVTTFEV ENIPLNTKI 17 353 PSIDIRYV TTFEVPVSV AEDGGRVSR 388]KDADHNGRV | GQVSNTTF STNPGTVVF 1 428STKEYAIKL KHSPKNLLL ]KDENDNAPV Table XXXII-109P1D4 8 GEIFTTGAR 1 PDAPPEFSL v.1-B4402-9-mers EDINDNAPL 5 PPLTSNVTV Each peptide ISIPENSAI ELL portion of SEQ ID NO: F46 PLTSNVTVF 3; each start position is 52SAINSKYTL VFTHNEYNF specified, the length of ELIKSQNIF 1 F-1 peptide is 9 amino F27________ ENLPRHGTV acids, and the ADIGENAK 8]LPRHGTVGL position for each 429TKEYAIKLL 5 D9 flYNA peptide is the startGMLTVVKKL 16 ________ H__ position plus eight. F-0 621QTGVIRPNI AKDNGVPPL 635KQESYTFYV EETPNHKLL AEVRYSIVG 6 PPSNCSYEL EEMPENVLI 6 28 QETGNITLM16 71 IVGGNTRDL QELPLDNTF 6 897DSDGNRVTL 720TRDLFAIDQ DEFRLVKI ENVLIGDLL 15 7ITLMEKCDV [ 45 DENDNAPVF ~4 KSLTTAMQF 15 WO 2004/098515 PCT/US2004/013568 184 Table XXXII-109P1D4 Table XXXIIII-109P1D4 Table XXXIIlI-109P1D4 v.1-B4402-9-mers v.1-B5101-9-mers v.1-B5101-9-mers Each peptide is a Each peptide is a Each peptide is a portion of SEQ ID NO: portion of SEQ ID NO: portion of SEQ ID NO: 3; each start position is 3; each start position is 3; each start position is specified, the length of specified, the length of specified, the length of peptide is 9 amino peptide is 9 amino peptide is 9 amino acids, and the end acids, and the end acids, and the end position for each position for each position for each peptide is the start peptide is the start peptide is the start position plus eight. position plus eight. position plus eight. 7 EEDTGEIFT 15 [ NATTGLITI [26 106 CFYEVEVAI 19 114 ILPDEIFRL 15 PPLTSNVTV 26 152TSAINSKYTL 19 120 FRLVKIRFL TPLNSKHH EGDKMPQLI 129 IEDINDNAP 1115 LPDEIFRLV APVFTQSFV ENSAINSKY 151 DPDVGINGV 583 LPRHGTVGL 19 68VGINGVQNY 1 656SAKVTINVV 24 99 YGDNSAVTL19 179 IKSQNIFGL 1[[ALPSTNPGTV 241 708 NAEVRYSIV 19 20KELREEK NPGTVVFQV 820GTITVV 9 29 LVSNIARRL 15 F81I VAGTITVVV DGNRVTLDL 9 307GLITIKEPL 15 FAVLLACVV 23 52 IPNKSLTTA 18 32NPVNDTVVL 1[35[NAPLFPATV 23 8GARIDREKL 1 374IPLNTKIAL 15LPAAVDPDV 17 DEIFRLVK 4 IPFRLRPVF 15 FPQRSSTAI 38 LFPATVINI18 4 QFLLETAAY TPNHKLLVL 336 PARAMVLVN18 599YGDNSAVTL 352 VPSIDIRYI 380 IALTVTDK 623 GVIRPNISF 792APVTPNTEI 89DADHNGRVT 7 LFSIVNL 15 SPTSDYVK RPVFSNQFL 18 7 TNATLINEL 15PATVINISI 444PPLNQSAML 86 PTSDYVKL AAVDPDVGI 586HGTVGLITV 182 GTITVVVVI 1261HPVFKETEIl2 0 DNSAVTLSI 1 880 NLLLNFVT IPLNTKIAL 22 760DSLFSVVIV 18 912EEQTMGKYN 475IPENNSPG LVAAVAGTI 9SKHHIlQEL 15181SPGIQLTKV ~j96LPLDNTFVA 1 PGTVVFQVI YPVTTFEVP18 Table XXXIIII-109P1D4 75 QPDSLFS 22 171 NGVQNYELl 17 v.1-B5101-9-mers 816AAVAGTITV 347DVNDNVPSI Each peptide is a ________ F_________ portion of SEQ ID NO: ] NPVNDTVVL 438AADAGKPPL 3; each start position is TPNTEIADV 440DAGKPPLNQ specified, the length of 819AGTITVVVV 21 547 VPPLTSNVT peptide is 9 amino F8_______ __________ acids, and the end 69 TGDVPLRI 22 ITVVVVIFI position for each DTYVMKVKV 1NLLLNFVT1 peptide is the start MPARAMVLV 20 SGTYFAVL16 position plus eight. __4___9 __6]_ ___3__9]__F9 ]GPNAKINYL FPATVINS 16APLFPATVI 7(71 NATLINELV 2120 DREEKDTYV16 [2IGAQEKNYTIl DPYSVSDCG [0[22TAILQ VS VT [ WO 2004/098515 PCT/US2004/013568 185 Table XXXIIII-109P1 D4 Table XXXIII-109P1D4 Table XXIll-109P1D4 v.1-B5101-9-mers v.1-B5101-9-mers v.1-B5101-9-mers Each peptide is a Each peptide is a Each peptide is a portion of SEQ ID NO: portion of SEQ ID NO: portion of SEQ ID NO: 3; each start position is 3; each start position is 3; each start position is specified, the length of specified, the length of specified, the length of peptide is 9 amino peptide is 9 amino peptide is 9 amino acids, and the end acids, and the end acids, and the end position for each position for each position for each peptide is the start peptide is the start peptide is the start position plus eight. position plus eight. position plus eight. 338RAMVLVNVT IADVSSPTS [742]TDLGLHRVL 14 F4.04 IPFRLRPVF AVAGTITVV 59PDSLFSVVI 9DADSGPNAK VPVSVHTRP 7 VNLFVNESV|1 508 DAPPEFSLD 30 IREEMPENV 1 89DVDSDGNRV 5 DCRTGMLTV 6 72 VPLIRIEED1[9 DSDGNRVTL14 ]GMLTVKKL r83 EIFTTGAR 14 676] PPSNCSYEL [16 11561 SKYTLPAAV 14 Table XXXIV-1 09P1 D4 LGLHRVLVK 1 PAAVDPDVG v.1-Al-10-mers 791 EAPVTPNTE 16 182 QNIFGLDVI Each peptide is a 973 VACDSISKC EKDTYVMKV portion SEQ N F9991 TTFEVPVSV 6 258 IPENAPVGT specified, the length of MDLLSG_ 5_ ADIGENAK _ peptide is 10 amino [IIMLSTY ~ 7 AIEAI1 acids, and the end [14ILACVVFHSG 3 LASDGGLMP position for each peptide 34MPENVLIGD LMPARAMVL 4 is the start position plus 59TAMQFKLVY MVLVNVTDV 4] nine. [671 YKTGDVPLI VNPVNDTVV 4 LLETAAYLDY32 ] DREKLCAG 5 366 DTVVLSENI 4 48IPENSAINS ENIPLNTKI TTAMQFKLVY F1742342LD]YE4T23Y 28 17 fYELIKSQNIjfj 41AAYLDYEST 1452LDYESKEY 2 FGLDVIETP 4 YESTKEYAI '1 LEE KY 98MPQLIVQKE 432 YAIKLLAAD 4E E494 GKY27 261NAPVGTSVT LAADAGKPP 10DnSY2 [6 APVGTSVTQ lI45VFTQSFVTV 1420SEDREEKQESY L 275]DADIGENAK 1 TQSFVTVS5 ED RDY 313EPLDREETP 93 ADSGPNAK14 5 VPDY 36DIRYVNPV APPESLC 673 FVPPSCSY _21 IVNPVNDTV 539TlLAKDNGV [4 F704 P Y 2 4SAMLFlKVK j~ 4 LAKDNGVPP 14~TDINARY 5CRTGMLTVV 1!59VPENLPRHG 14T8 SDYSVLV 12 2KEDKYLFT1 PRHGTVGU SSDPYVSD 5SNVTVFVSI 1557PDYGDNSAV A~ 21 TVDP[G 57DPDYGDNSA !LDENDFTI 5 S P E 21 644KAEDGGRVS 15TIDSQTGVI 1NSPVLEY 1 F MNAEVRYSi VNDNKPVFI ~S 6PDE LV DQETGNITL IAVDNDTGM 9PENSAINKY WO 2004/098515 PCT/US2004/013568 186 Table XXXIV-1 09P1 D4 Table Ta v.1-A1-10-mers A0201-10-mers v.1_A_201_10_mers Each peptide is a Each peptide is a portion Each peptide is a portion portion of SEQ ID NO: of SEQ ID NO: 3; each of SEQ ID NO: 3; each 3; each start position is start position is start position is specified, the length of specified, the length of specified, the length of peptide is 10 amino peptide is 10 amino peptide is 10 amino acids, and the end acids, and th end cis, an the end position for each peptide position for each peptide position for each peptide is the start position plus is the start position plus is the start position plus nine. nine nine _ _ _ _ I] _ __ ] 239 VTDTNDNHPV38 VLIGDLLI<DL 251FLIPNKSLTTA 3 ATDADI.GENA 1 DEIFRL 60AMQ5KLVYI(T 20 345 VTDVNDNVPS fjl FAVLLACV 2233 AILQVSVTDT 20 429 TKEYAIKLLA1 GINGVQNYEL 2529 NLVSNIARRL 2 7411 VDLGLHRVL 42 DLLKDLNLSL 24 428 STKEYAIKLL 20 78 STEAPVTPNT g 43 LLKDLNLSLI:2 437 20 897 DSDGNRFTLD 7118 LIKSQNIFGL M 560 F191 SGAQEKNY 3G 92 G20 F07FYEVEVAILP 39 T 4 756 LGQPDSLFSV 20 385 DKDADHNG69 20 399 DHEIPFRL 824 40 OEIPFRLRP 56STAQK 396 IEPDT 2 SNEIADVSSPLVYKGDVP 94TLDLPIDLEE 32 LLSGL2 0 FEEAL1 0 FGDLLKDLNL582 23 127 E N 44 LKDLNLSLIP 68 LSNGV2 5 IEAVT1 67 DGINGQNY 735 23 283 F19 194 EGDKMPLIV 7761 T355 19 329 ASDGGLMPAR 137 N360 514 SLDCRTHMLT 334 22 569 THNENFY 35 9Y 221 538 F191 GLITVTDPDY 655 N 801 ADVSSPTSDY|74 IGNRD V177IVLVEV 1 812KLAVG 22 r8- 1 AVGV1 Table XXXV-1 09P1 D4 8 V 2821 T 19 v.1-A0201-10-mers 817 G 22 887 TIEEKADDV1 Each peptide is a portion 882 of SEQ ID NO: 3; each start position is 48 NLSLIPNKSL 21 164 G specified, the length of 262 G 18 peptide is 10 amino 185T 2 H acids, and the end F position for each peptideVL is the start position plus 706 V 2369 S 18 nine H Tabl XV-109P1D4 -V 794 2 VT N EAV 2 34 ILN KIL 18 pepe VI 1a4mi 18 761l SLFSVVIVNLJ 29H2 IEMEV10 ~ ~ SGQTV 1 WO 2004/098515 PCT/US2004/013568 187 Table XXXV-109P1 D4 Table XXXV-109P1 04 Table XXXV-1091 04 v.1-A0201-10-mers v.1-A0201-10-mers v.1 -A0201 -1 -mers Each peptide is a portion Each peptide is a portion Each peptide is a portion of SEQ ID NO: 3; each of SEQ ID NO: 3; each of SEQ ID NO: 3; each start position is start position is start position is specified, the length of specified, the length of specified, the length of peptide is 10 amino pepfde is 10 amino peptide is 10 amino acid s, and the end acids, and th end acids, and th end position for each peptide position for each peptide position for each peptide is the start position plus is the start position plus is the start position plus nine nine nine 48 GIQLTKVSAM 4 PVFTQSFVTV 16 230 SSTAILQVSV 15 59PLTSNTVFV J514 SCRTGML 1265 GTSVTLHAT 15 650RVSRSSSAKV 519 15 657AKVTINVVDV 540 1328 LASDGGLMPA 740 DVTDLGLHRV 1 559S 16 332 15 780 TLINELVRKS 1 [585 RHGTVGLITV 6 346 511 781 LINELVRKST E18 616 FTIDSQTG-VI 1379 KIALITVTDK 1 785 LVRKSEAPV684 399 VLLACVFHS 689 TNPGTVVFQV 16 435 KLLAADAGKP1 13LLACVVFHSG 17 9 IVNTM1 5 KEDAV1 34DNAPLPATV 724 16 490 45 NISIPENSA726 6 492 336PARAMLVNV 17 742 16 515 LNTKIALITV 547 131ALITVIDKDA 17 6 INFNS1 7 TNYFV1 145PLNQSAMLFI 17 0 YKLAV1682YKEGR s 46FTQSFVTVSI 17 2 IIAVC1 6 VDKVI1 SGPNAKINYL1783VRCQHL166VNNVIV5 15031 YLLGPDAPPE 87 PNLNV1 68SNGWQ1 LLGPDAPPEF 5 68SILDENDDFT 2 8 LNVIE1 2 IQTNT1 72NITLMEKCDV 17 9 DDNVL[ 4 TLLRL1 TLMEKCDVTD 1 7 625 VIFITAVV 17 2 TKDPL16 6 LVEVN1 98VTTFEVPVSV f2 4JSSQAQ f189ATTVI1 75IRIEEDTGEI 16 Q~ LSTIAW 7 NLNVI1 19IFRLVKIRFL M TIALAIh 5 SH!QL1 13AINSKYTLPA 9 1SAENT 5 8 SSDYV1 21STAILQVSVT WJ4 LLLPK1 9 GPTFV1 29VTDTNQNHPV R 1IRKLAI1 1HLNATIGLIT 39ETPNH LLVL ~ 5 SISYL1 .- 00-0mr Ta87 XX-191D9 351-6 F8SQIY 2-7] 1181 6QN-65] W 34 S 8o1f SEQD NO: 3eh pep4 Ed 8 R0 I 1amn F6acids and the en6 position for each pepid is 1 the15 star postinlu Fil 91 r S6ilDQFDNSP F-RHGTVGLITV P _6 , F1-3] [15] TblV AVDI-DTGMD F3-191 H ~ ~F AIQTN -51 11V1-O0-0m F3-DQETGNITL11 F3TDLGLHRVLV51

LGLRFVK

WO 2004/098515 PCT/US2004/013568 188 Each peptide is a portion Table XXXVI-1 09P1 D4 Table XXXVI-1 09P1 D4 of SEQ ID NO: 3; each j -A03-1-mers [ v start position is Each peptde is a portion Each peptide is a portion specified, the length of of SEQ ID NO: 3; each of SEQ ID NO: 3; each peptide is 10 amino start position is start position is acids, and the end specified, the length of specified, the length of position for each peptide peptide is 10 amino peptide is 10 amino is the start position plus acS' and the end aci , and th end nine position for each peptide position for each peptde [ __________ is the start position plus is the start position plus 154 INSKYTLPAA IF nine nine 413 SNQFLLETAA 1H I1 I__ __ _ 430 KYAIKLLAA 19 429 TKEYAIKLLA 1128 EDNAP 9 SDYVKILVAA 441 A133 NDNAFPA 836 CRQAPHLKAA 454 E1 S330SDGGLMPARA 1481 PGIQLTKVSA 10 225Q 432 YAIKLLAADA 1484 QLTKVSAMDA 110 2 Y810 YVKILVAAVA 19 490 12651 GTSVTQLHAT L1 N155 KYTLPAAV 500 1268 41 NFLLEAAY 533 E274 EAIKLLAAD 10 288 DVKILAAV 636 296 8 RAPHLAAQ F 648 [2] DLLSGTYIFA691 10 329ASDGGLMPAR [6[GTIlFAVLLA 11170ADDGN 031DGMAA j SLACVVFSGA10 IAL 1 LPNKSLTTA 10 382 [801DIGEIFTTGA 0 770 S 4 E E E1 89 ARIDREKLCA 1783N 10 433 9 104 CFYEEVA 7 T 1442 12 FLIEDINDNA 807 TSDYVILVA 1 F455 KVKDENDNAP F2 IDNAPLFPA 482 1 INISIPNSA 0 83 153 NSKYLPA H 835 F 1 1 224 FPQRSTA 10 86W 10 5 253 EVSIENA 0 884 L 264 TSVTQLHA| 9 596 2 S67 TQLHATDA 10 9 PDLARHYKSA 10 637 27 DADIENA C101 938 49 SESNLVNIA65 LPLDNTFVA 92 12IARRLFHLNA C~~ LGYFV~71VNTMA ~ 320TNHKLLVLA i I SLASDGGLMPACVVFHSGAQ l 372 ENIPLNIIA I 31ALITVTDKDA 108 GITTA(8 LVKTA 42FSNQFLLETA 109 IREL( PTNEA 4Tab[e HXXX VVI 9P [LDYES~ffv.1-A0203-10-mers.1 Eac petdeiAaprto WO 2004/098515 PCT/US2004/013568 189 Table XXXVI-109P1D4 Table XXXVll-109P1D4 Table XXXVII-109P1D4 v.1-A0203-10-mers v.1-A3-10-mers v.1-A3-10-mers Each peptide is a portion Each peptide is a portion Each peptide is a portion of SEQ ID NO: 3; each of SEQ ID NO: 3; each of SEQ ID NO: 3; each start position is start position is specified, start position is specified, specified, the length of the length of peptide is 10 the length of peptide is 10 peptide is 10 amino amino acids, and the end amino acids, and the end acids, and the end position for each peptide position for each peptide position for each peptide is the start position plus is the start position plus is the start position plus nine nine nine 1 [824] V 19F4 6 DLNLSLIPNK 21 [-4 PVFTQSFVTV H 4 VVIFTAV K 220 0VEDGGFPQR LLGPDAPPEF 18 8 TAVVRCRQAP GLMPARAMVL 2 RTGMLTVV SKKQNSWAT[ KLLAADAGKP V6l24 VIRPNISFDR1 885 FMTIEEIKAD QVIAVDNDTG 28 KVTINVDVN 928 FKPDSPDLAR QAPHLKAAQK IVPPSNCSYE 1934 DLARHYKSAS] KLVYKTGDVP F8j 7 AVDNDTGMNA 18 9YKSASPQPAF]9 73PLIRIEEDTG 2079NLFVNESVTN 1 LPLDNTVAC 76 RIEEDTGEIFT 20 F825]AVV 196 DKMPQ4VQK ]MIMMKKKK Table XXXVI-109P1D4 3 IVNPVNDTW DLEEQMGKY Each peptide is a portion 478NNPGQLTK 934DLAR SAS [ of SEQ ID NO: 3; each 487KVSAMDADSG DLLKDLNLSL start position is specified, CRTGMLTVVK GPRDEHCFY the length of peptide is 10 amino acids, and the end T5V23 VKKLDREK 121RLKILIE 1 position for each peptide 5 ILAKDNGVPP DVGINGVQNY is the start position plus 6 RVSRSSSAKV QLHATDADIG 1 nineF 7 ATLINELVRK 0 LITIEPLDR 7 D4L3GLR CWFHSGAQE 1PLDREETPNH 17 [1F1AVVRLPDEFRLVK 1143EIPFRLRPVF 17 8261 F2VI]T4V0R3] 17 FRLRPVFSNQF 63AVDPDVGING AIKLLAADAG 1 F4 DVIETPEGDK 2 REEKDTYVMK 1QSAMLFKVK R A[ YLDYESTK ~i111LLETAAYLDY EJ[0[YLL~GPDAPPE 117 1AVLLACVVFH 54DKYLFTILAK 19[21MLTVVKKLDR FS 5 SLIPNKSLTT GLITVTDPDY TILAKDNGVP 3 KALITVTDK TIDSQTGVIR GVPPLTSNVT 1 817AVAGTITVW GVIRPNISFD NLPRHGTVGL 17 FHSGAQEK FIVPPSNCSY 609ILDENDFTI 2ELDREEKDTY [][75[IVGGNTRDLF [Il65KQESYTFYVK 17 8 AVVRCRQAPH TLMEKDVTD 6 YVAEGRV [20jQLJVQKELDR [~ 6[LVYKTGDVPL EtL1TVFQVIAVD L17 __RLFHLNATTG [ ~KVKVEDGGFP~a WF]V QVIAVDNI[P F K LDRE KED HLNATTGLIT 1LVKANDLGQP YV1KLVAAVAK ~ 136 LVLASDGGLM VV176 IVNLFVNE 17l [Tj[ILAVA12 32 VLASDGGLMP 1883VSSPTSDYVK 17 H31 IMMAGT II 34IKLLAADAGK 1 84 LVAAVAGTIT El WO 2004/098515 PCT/US2004/013568 190 Table XXXVIl-109P1D4 Table XXXVII-109P1D4 [Table XXXVIl-109P1D4 v.1-A3-10-mers v.1-A3-10-mers L v.1-A3-10-mers Each peptide is a portion Each peptide is a portion Each peptide is a portion of SEQ ID NO: 3; each of SEQ ID NO: 3; each of SEQ ID NO: 3; each start position is specified, start position is specified, start position is specified, the length of peptide is 10 the length of peptide is 10 the length of peptide is 10 amino acids, and the end amino acids, and the end amino acids, and the end position for each peplide position for each peptide position for each peptide is the start position plus is the start position plus is the start position plus nine nine nine 870KKKKKKHSP IPENSAINSK 27 FLIEDINDNA 1 949 QPEIELNS SKYTLPAAVD 42 TV1NISIPEN -1i 37NVLIGDLLD SIPENAPVGT 1531 AINSKYTLPA 4 901RIDREKLCAG F 67 SVQLHATDA L HA]EKDTYVMKVK 1 95 KLCAGIPRDE F2-7-]AD6GENAKlH 523311 AIL QVSVTDT 14 11111 EVAILPDEIF 1 Fjj LDREETPNHK 15 12551FEVSIPENAPV 14 1-51 AILPDEIFRL 6324jjljKLLVLASDGGi PVGTSVTQLH 234ILVSVTDTN VLVNVTDVND 3 SIDIRYlVNP 21DTNDNHPVFK NVTDVNDNVP TVTDKDADHN 291LVSNIARRLF DVNDNVPSID RVCFHE 14 34MVLVNVTDVN DIRYVNPVN 49MDASGPNAK [3PVNDTVVLSE 39VLSENIPLNT 1560KINYLLGPDA 14 35PLNTKIALIT ~J30LSENIPLNTK 1554 PLTSNVTVFV 14 ALITVTDKDA KDENDNAPVF PVFTHNEYNF 1 FLLETAAYLD SLDCRTGMLT AVTLSILDEN 14 23YLDYESTKEY [ SIDQNNSP GRVSRSSSAK 46LLAADAGKPP ~ 661RPNISFDREK Is 11EVRYS1VGGN 114 45KVKDENDNAP [4 641KAEDGGRVSR 75ADQETGNIT 14 4QLTKVSAMDA [T(PVFIVPPSNC 11175GLHRVLVKAN 14 IKKLDREKEDK [4 641LVLPSTNPGT EI70TLINELVRKS 14 5 DVNDNKPVFI SLFSVVIVNL 7 ELVRKSTEAP 5VLSTNPGTV IVNLFVNESV PVTPNTEIAD 14 712RYSVGGNTR PENRQMIMMK EIADVSSPTS 722DLEA ETG RQMIMMKKKK TVVVVIFITA 14 748RVLVKANDLG 863QMIMMKKKKK 834VRCRQAPHLK 7SVVIVNLFVN [j90IQPETELNSK 15IJEN-RQMIMMKKl14 7 LVRKSTEAPV HIQELLDN 879] KNLLLNFVT 8 KIAAVAGT ELPLDNTFVA 880NLLLNFVTIE 131VVRCRQAPHL 41104PVSVHTRPVG I I83LNEVTIEETK 14 902RVTLDLPIDL IO PVQVSNTT 15 895DVDSDGNRVT [991IDLEEQTMGK [4 2jVLLACVVFHS 1194TLDLPIDLEE 14 [lSVSDCGPVT [1F ENVLIGDLLK 1496DLPIDLEEQT 14 38 VLGDLLKDL 51 LINKSLTTA 14 967PLDNTFVACD 4LLKSDLNLSLI [4 8TTAMQFlKLVY 1491TFVACDSISK 14 5KSLTTAMQFK ~ 9TAMQFKLVYK 1[92!FVACDSISKC[1 [11ElFRLVK IRF [1141KIRFLIEDIN [41911SIS~KCSSSSS 114 WO 2004/098515 PCT/US2004/013568 191 Table XXXVil-109P1D4 Table XXXVIII-109P1D4 Table XXXVllI-109P1D4 v.1-A3-10-mers v.1-A26-10-mers v.1 -A26-1 0-mers Each peptide is a portion Each peptide is a portion Each peptide is a portion of SEQ ID NO: 3; each of SEQ ID NO: 3; each of SEQ ID NO: 3; each start position is specified, start position is specified, start position is specified, the length of peptide is 10 the length of peptide is 10 the length of peptide is 10 amino acids, and the end amino acids, and the end amino acids, and the end position for each peptide position for each peptide position for each peptide is the start position plus is the start position plus is the start position plus nine nine nine 997 PVTTFEVPVS5 TTAMQFKLVY 14 761 SLFSVVIVNL 18 911ETPEGDKMPQ VVRCRQAPHL Table XXXVIII-109P1D4 213DTYVMKVKVE ETPLNSHHI v.1-A26-10-mers EVSIPENAPV 3EMPENVLIGD Each peptide is a portion r347]DVNDNVPSID A20 113 AILPDEIFRL 17 of SEQ ID NO: 3; each P start position is specified, 366 DTVVLSENIP 178 LIKSQNiFGL 17 the length of peptide is 10 494DSGPNAKINY DTNDNHPVFK amino acids, and the and E___________ position for each peptide 555 TVFVSI1DQN 2262 APVGTSVTQL 1 is the start position plus 873 FIVPPSNCSY 20 293 SNIARRLFHL 17 nine 737 EKCDVTDLGL P363 PVNDTVVLSE 17 776 VTNATLINEL 20 554 VTVFVSIIDQ 17 DVGINGVQNY RVTLDLPIDL 32DREKQESYTF 1 319] ETPNHKLLVL 9 TTFEVPVSVH [SJ 1 7141 SIVGGNTRDL [ 1 EVAILPDEIF 12 EVPVSVHTRP 2 SVTNATLINE L Ii][EIFRLVKIRF ~ 121TVINISIPEN DYVKILVAAV 117 704DTGMNAEVRY 2ETEEVSIPE 8 TVVIFITA 181DVIETPEGDK D(I6IREETPNHKL19 LICVFHSGAQE N6 EVRYSVGGN 1GVIRPNISFD EEMPENVLIG I19IEVEVAILPDE DVNDNKPVFI 11l(71NVLIGDLLKD 16 30DNVPSIDIRY [6911TVVFQVIAVD 1[38VLIGDLLKDL 1 37TVVLSENIPL 2 761 SVVIVNLFVN 11117DEIFRLVKIR 1 7DVTDLGLHRV [][IDVSSPTSDYV 11112GVQNYELIKS 1 0 GTITVVVVF VVFITAV 1 EEKDTYVMKV6 2DIGENAKIHF [91DVDSDGNRVT [~I39ITIKEPLDRE 1 STKEYAIKLL DPYSVSDCGY FTDHEPFRL 0ETKADDVDS DLLKDLNLSL PVFSNQFLLE 7 DVPLIRIEED ~ 5LVYKTGDVPL 1852LTVVKKLDRE 1 130EDINNAPL TEFTTGA 52DREKEDKYLF 16 [43JEIPFRLRPVF ~ 3EIFTTGARID 18511EKEDKYLFTI16 PVFTHNEYNF LVSNIARRLF 1ENDFTIDSQ ETGNITLMEK 19ETAAYLDYES 662 DVNDNKP6 1DLEEQTMGKY DNAVFTQSF VTDLGLHRVL 16] ELDREEKTY EYNFYVPENL 18 75LVKANDLGQP ESTKEYAIKL ]DYGDNSAVTL 18 1 EIADVSSPTS [611DNSAVTLSIL jj162[GTVVFQVIAV 1j81ADVSSPTSDY 1 [TTFKPDSPDL jI1T[IVGGNTRDLF [LJ121ITVVVVIFIT 1 WO 2004/098515 PCT/US2004/013568 192 Table XXXVIll-109P1D4 Table XXXIX-09P1D4 Table XXXIX-109P1D4 v.1-A26-10-mers v.1 -B0702-10-mers v.1-B0702-10-mers Each peptide is a portion Each peptide is a portion Each peptide is a portion of SEQ ID NO: 3; each of SEQ ID NO: 3; each of SEQ ID NO: 3; each start position is specified, start position is specified, start position is specified, the length of peptide is 10 the length of peptide is 10 the length of peptide is 10 amino acids, and the end amino acids, and the end amino acids, and the end position for each peptide position for each peptide position for each peptide is the start position plus is the start position plus is the start position plus nine nine nine _ _ _ _ _ _ L __ 972 FVACDSISKC V 547 VPPLTSNVTV LPAAVDPDVG 1006 SVHTRPVGIQ E[9DPDYGDNSAV 8 282 AKIHFSFSNL 1 [6P761PPSNCSYELV 18 3 EPLDREETPN 13 Table XXXIX-1 09P1 D4 856TPNPENRQMI GLMPARAMVL v.1-B0702-10-mers F945 I QPAFQIQPET 1 362 NPVNDTVVLS 13 Each peptide is a portion 103VVVTP 8 3 ADGPL1 of SEQ ID NO: 3; each VPVSVHTRPV LDAGKPPL start position is specified, 1139I FPATVINISI 17 480 SPGIQLTKVS 13 the length of peptide is 10 579 VPENLPRHGT 1541I LAKDNGVPPL tL3 amino acids, and the end portion for each peptide 87 SPKNLLLNFV 1 F 82 1 NLPRHGTVGL is the start position plus 72 VPLIRIEET DYGDNSAVTL nine 444PPLNQSAMLF 16DNSAVTLSIL 262PPEFSLDCRT PSNCSYELVL 858NPENRQMIMM 1[4jSIVGGNTRDL 13 12TPEGDKMPQL I1071LPIDLEEQTM I1LMEKCDVTDL M FPQRSSTAIL 5 TPLNSKHHI 737 EKCDVTDLGL I 4KPPLNQSAML ~ isJLPDEIFRLVK II73ANDLGQPDSL 1 5GPDAPPEFSL 2 1IAPLFPATVIN 1l83VVRCRQAPHL 1 5IPNKSLTTAM [IMPARAMVLVN jf(84KKHSPKNLLL 13 409RPVFSNQFLL KEDKYLFTIL KPDSPDLARH 496GPNAKINYLL AVAGTITV 80 SPTSDYVKIL VDSDGNRVTL Table 34MPENVLIGDL LSGTYFAVL XL I1 9 PLVKE -8]______ 109P1 D4 MPQLVQKE4 IGDLLKDLNL v.1 -BOB VPPSNSYEL 65LVYKTGDVPL 1 10-mers LPSTNPGTVV IFRLVKIRFL SQPDSLFSI IEDINDNAL 14 No RPGQFN o___716___Pd_ Results RPVh1 lQVSNT 39ETPNHKLLVL 14 F___________ Found. SVPSIDIRYV 361VNPVNDTVVL 4PVTQFV 4F Table fPPLTSNVTVF SDGNRVTLDL 1

XLI

a3]LPRHGTVGLI F QP7EP 1 109P1D4 _____F9__ v.1 69 NPGTVVFQVI 959KHHIQELPL 14 B1510 APVTPNTEIA LPLDNTFVAC 10-mers 9YPVTTFEVPV l[][DLLKDLNLSL[1I 320TPNHKLLVLA IPRDEHCFYE No [74 IPLNTKIALI jAILPDEIFRL Results WO 2004/098515 PCT/US2004/013568 193 Found. Table XLIV-109P1D4 Table XLIV-109P1D4 v.1 -B4402-10-mers v.1-B4402-10-mers Table Each peptide is a portion Each peptide is a portion XLIl- of SEQ ID NO: 3; each of SEQ ID NO: 3; each 109PI D4 start position is specified, start position is specified, v.11- the length of peptide is 10 the length of peptide is 10 B2705- amino acids, and the end amino acids, and the end 10-mers position for each peptide position for each peptide is the start position plus is the start position plus nine nine No Results Found. 633 REKQESYTFY 20 F206 ELDREEKDTY 1[g 110 VEVAILPDEI EEKDTYVMKV 15 Table 32 EEMPENVLIG 1 291 LVSNIARRLF 15 XLIll- 78 EEDTGEiFTT 1293 SNIARRLFHL 15 109P1D4 130 EDINDNAPLF 3 ADHNGRVTCF v.11 B2709- 40 HEF 1403 EIPFRLRPVF 15 1 0-mers AEVRYSIVGG RLRPVFSNQF 1 VLIGDLLKDL ESTKEYAIKL 15 No _____38 ____]_ F4271 _______ Results 282AKHFSFSNL KEYAIKLLAA Found. EETPNHKLLV NLPRHGTVGL 15 ETPNHKLLVL VDSDGNRVTL Table XLIV-109P1D4 NQFLLETAAY 941SASPQPAFQ v.1-B4402-10-mers STKEYAIKLL PETPLNSKHH 6 Each peptide is a portion 4 SGPNAKINYL SGTYFAVLL 14 of SEQ ID NO: 3; each [6]SFVIN 7)L2.IHGQKYP start position is specified, S VIFGEN Y 14 the length of peptide is 10 DEIFRLVKIR MPEVLI411 mino acids, and the end EFRLVKIRF 11YEVEVAILPD position for each peptide 25 TEESPE 6[Tf[ L DET14 is the start position plus TESP K E nine 262APVGTSVTQL 350 NVPSIDIRY 4 Ii ___________1 33GLMPARAMVL 16r51NVPSIDIRYI [74 3REETPNHKLL )[33NIPLNTKIAL 1[1IVNPVNDTVVL |9) 46PENNSPGQL I 59TGMLTVVKKL 16IPLNTKIALI 14 52KEDKYLFTIL 151AEDGGRVSRS [LI[9)TCFTDHEIPF [LG 9EEQTMGKYNW )5JANDLGQPDSL L6 ~[YLDYESTKEY 14 16YELIKSQNIF ~ 70)TEAPVTPNTE 11[[PPLNQSAMLF 14 73NESVTNATLI [1821GTITVVVVIF 1 ~ fKDENDNAPVF 14 I. IPENVLIGDLL 1190)PDSPDLARHY 1)46][DNAPVFTQSF 14 6GE]FTTGARI FEVPVSVHTR 4 DSGPNAKINY [19[IEDINDNAPL ~j 4 QEKNYTIREE 15[0]LLGPDAPPEF 14 [19)PENSAINSKY 48 NLSLIPNKSL 15)i]PEFSLDCRTG 14 19)PEGDKMPQLI li5 NKSLTTAMQF 15K711LDREKEDKY 14 (j)REEMPENVLI ) 19IFRLVKIRFL 154]PPLTSNVTVF fG AGIPRDEHCF VKIRFLIEDI GLITVTDPDY 14 AILPDEFRL PLFPATVINI DYGDNSAVTL 14 29GENAKlHFSF fi[9)IETPEGDKMP 67LSILDENDDF 14 31SENIPLNTKI LO)KELDREEKDT 15)11FTIDSQTGVI L4 WO 2004/098515 PCT/US2004/013568 194 Table XLIV-1 09P1 D4 Table XLIV-109P1D4 Table XLIV-1 09P1 D4 v.1-B4402-10-mers v.1-B4402-10-mers v.1-B4402-10-mers Each peptide is a portion Each peptide is a portion Each peptide is a portion of SEQ ID NO: 3; each of SEQ ID NO: 3; each of SEQ ID NO: 3; each start position is specified, start position is specified, start position is specified, the length of peptide is 10 the length of peptide is 10 the length of peptide is 10 amino acids, and the end amino acids, and the end amino acids, and the end position for each peptide position for each peptide position for each peptide is the start position plus is the start position plus is the start position plus nine nine nine F871PSTNPGTVVF ]5311 EKEKYLTl 12261 FPQRSSTAIL 13] SVGGNTRDL NSPVFTHNEY 131 [240 D TDTNDNHPVF 12 737EKCDVDLGL PVFTHNEYNF F [0 KETEIEVSIP 12! VTDLGLHRVL 114] 57 NEYNFYVPEN 1299 LFHLNATTGL l [77(NDLGQPDSLF [574 EYNFYVPENL 13 [0]1 FHLNATTGLI 1 F762jj LFSVVIVNLF I1H 611 DENDDFTIDS 13 F21 LNATTGLITI 112 VTNATLINEL j1j60SFDREKQESY 1136!DREETPNHKL 1 AVSSPTSDY 1i66QESYTFYVKA 13ITVVLSENIPL jj[SPTSDYVKIL 63FIVPPSNCSY 13 1391FTDHEIPFRL 12 I 1j[AGTITVVVVI 75IVGGNTRDLF 1[47!LLETAAYLDY 12 tAQKNKQNSEW ~!74FAIDQETGNI 1146!YESTKEYAIK 12 85]PENRQMIMMK 1]78QETGNITLME 13[JLDREKEDKYL 12 [~~IKKKKHSPKNL 1]77HRVLVKANDL 1 41!LAKDNGVPPL 12 KNLLLNFVTI l 9 TEIADVSSPT 1151!IDQNDNSPVF 12 I [SDGNRVLDL [i84SSPTSDYVKI 131~!PENLPRHGTV 12 [~[NSKHHIlQEL [j83KKKHSPKNLL 1 1!DNSAVTLSIL12 94[QELPLDNTFV 84KKHSPKNLLL 13[ [SRSSSAKVTI12 !SDCGYPVTTF [1386HSPKNLLLNF 1[i VDVNDNKPVF1! 1321VGIQVSNTTF]I 89EETKADDVDS 131~[PSNCSYELVL1! 111MDLLSGTYlF 1j92RVTLDLPIDL 1 l!NPGTVVFQVI12 141LSGTYIFAVL 1!931YKSASPQPAF [3 7j[GGNTRDLFAI12 111FAVLLACVVF 1!97AFQIQPETPL 1[76!IDQETGNITL 12 IGDLLKDLNL 1j93ETPLNSKHHI 1311MEKCDVTDLG12 !6[SLTTAMQFKL 1193IQELPLDNTF 1 73!NELVRKSTEA 12 il[TGARIDREKL 13 0IREEMPENVL 1211TPNPENRQMI 12 IlslHCFYEVEVAI 314 DLLKDLNLSL 1188!IEETKADDVD 12 F35]NAPLFPATVI 1] 58 TTAMQFKLVY 1 [LEEQTMGKYN 12! 1 LIKSQNIFGL ]KTGDVPLIRI 1 NWVTPTTF1 18MPQLIVQKEL 11l1lIRIEEDTGEI 3 [21 TTFKPDSPDL 11VEDGGFPQRS 1!711IEEDTGEIFT 1j99KHHIIQELPL 12 25 IEVSIPENAP 1 931REKLCAGIPR 1190KCSSSSSDPY IL2 120NLVSNIARRL 1! GIPRDEHCFY 13 45QFLLETAAYL 11 EVAILPDEIF K2 Table KPPLNQSAML 1]NISIPENSAI 10P 1D4 DENDNAPVFT NSAINSKYTL 1 v.1 1FSLDCRTGML TPEGDKMPQL 1 B5101- WO 2004/098515 PCTIUS2004/013568 195 1 0-mers Table XLVI -109P1D4v1-DRB1 Table XLVI -109P1 4v.1D-vRB1 0101- 15-mers 0101- 15-mers No Each peptide is a portion of SEQ Each peptide is a portion of SEQ Ru ID NO: 3; each start position is ID NO: 3; each start position is specified, the length of peptide is specified, the length of peptide is 15 amino acids, and the end 15 amino acids, and the end position for each peptide is the position for each peptide is the Table XLVI -109Pl D4v.1-DRBI start position plus fourteen start position plus fourteen 0 101- 15-es___________I. _________ Each peptide is a portion of SEQ F41] GDLLKDLNLSLIPNK M-21 RYSIVGGNTRDLFAI 124 ID NO: 3; each start position is_____ _______________ specified, the length of peptide is F6i~ Q2KLVKTGPL IRF] F7451 LIHVLKN 24 15 amino acids, and the end 1104[ EHCFYEVVAI 25 760][DSLFSWIVN-LFVNE- F241 position for each peptide is the Fl176]1 YELIKSQNIFL [2I5] F8-22]1[ ITVVVVIFITAWVRC ]241 start position plus fourteen________1l 85[VTEKDIVS 88223 DGGFPQRSSTDAYKLQV LA9A0V0] GNRVTLDLPI| |4 I80j SYVILVAGT M F297 ARRLFHLNATTGLIT12 F9-][YNWVTTPTTFKPS H1 7ii TYIFAVLLACVVFHS |341 Il__ 26511 GTSVTQLHATDADIG ||34 I LLVLASDGG 2 F975]1 CDSISK 24 4821 GIQLTKVSAMDADSG| 33 I311ARAMVLVN g F3 ][ LLSGTYIFA 1 4981 NAKINYLLGPDAPPE |33 433 AIKLLAAAKPL 451 KDLNLSLIPNKST R23 42851 HFSFSNLVSNIARRL ||32 [A L EEDTGEFTTG F21853 HFSQNELKSQNIG 31) F58[ PENLPRHGTVGIT 25~ 1 29[ IEDINDNAPLFPATV 123 1l7-3] VQNYEUIKSQN IF 3 4-05l PFRLRPVFSNQFLLE30 F6-1[ NDDFTIDSQT| |3 015 NSAINS 111711~ ~ DE64VKRF0E 28 ! TFYVKAEDGGRVR 11l16711 DVGINGVQNELS23 11-7] DEIFRLVKIRF-LIED] |28 - f NSYTPAVDDV 21 730][ TGNITLMEKCD-VTDL] 25~ [281]1 NAKIHFSFSNLVN g F155 INSKYTLPAAVD-PDVG||28 2 12971 RRLFHLNATTGLITI 728! 74I SVVIVNLFVN g [289j[ SNLVSNIARRLFHLN F7101 EVRYSIVGGNTRDLF 28 8.-ll][ VKILVAAVAGTITVV Ig [41 LVNVTOVN NTEIAVSSPSDYV281 925][ PTTFKPDSPD-LARHY 25~ 349][ NDNVIPSIDIRYVP13 F797] NTEIADVSSPTSDYV] |28 8821 LLNFVTIEETKADDV ||28 936]IARHYKSASPQPAFQ 115I [370]1 LSENIPLNTKA 23 4 QPAFQIQPETPLNSK |28 ED NYTIREEMPE 4 379][ KIALITVTDKD 10-911 EVEVAILPDEIFRLV 2j L [ DLNLSLIPNKSLTTA ||27-1]1 EKEDKYLFTI [~T~JSNFLEMYDE j74][ LIRIEEDTGEIFTTG ]H~ 5 34][1 DKYLFTILAKDNGVP-]2 F4131SNQFLLETAAYLDYE 12 80711 TSDYVKILVAAVAGT 2 11 PDEF F71 VPPLTSNVT R23 F-9-0 RIDREKLCAGIPRDE r]261 D4] NISIPEN 630 [SFDREKQESYTF 3 [ll0-5 HCFYEVEVAILPDE g 322]NHKLLVLASDG 4 [64811 GGRVSRSSSAKVTIN] 23 Lji ATVINISIPENSAIN 1IKLLVLASDGGLMPAR 14 F66] VVDVNDNKPVFIVP-P2 LEI LDIETEGKMPL F3[2-][ASDGGLMPARAM7VLV 2141 F6691 NKPVFIVPPSNOCSYE 13 Fl8-1LDVIETPEGDKMP-QL] 26- F28811 FSNLVSNIARRLFHL [|32I]6DGGL|PARAMVN 679]1 NCSYELVLPSTNPGT 23 F401 KEYAIKLLAADAGKP 26 F35]1 RYIVNPVNDTVVLSEg 24801 CSYELVLPSTNPGTV 23! 431]1 EYAIKLLAADAGKPP g 472][ TVSIPENNSPGIQLT 241 782] INELVRIKSTEV 23! [~j[FTILKDNG F 26 f1--fl I11NNSPGIQLKSM 4 [F8-11 KILVAAVAGTITVVV 123 F381FTILAKDNGVPPT - 67I HNEYNFYVPEF4N8P8 11! []VSAMDADSGPNAI 24!1[-921 AGTITVVVVFTV 23) F5-fjHNEYNFYVPENLPRH] 26 DPDYGDNSAVTLSIL 26 [499][ AKINYLLGPDAPPEF 24 F8211 T-ITVVIFITAVVR 23 7381 KCDVTDLGLHRVLVK 26 586]HGTVGLITVT 824] VCRQ 23] [ j TVVVVIFITAVVRCR || [6)1 TINVVDVNDNKPVF2 [841!AAQKNKQNSEW 23 83 I TAWRCRQAPHLKAA 670]1 KPVFIVPPSNOSYEL 24! 91MGKYNWVTT 2 [33l EMPENVLIGDL-L-KDLg Eg 1li VIAVDNDTGMN=AEVR 94 [2lj IQELPLDNTFVADS] 23) WO 2004/098515 PCT/US2004/013568 196 Table XLVI -109P1D4v.1-DRB1 Table XLVI -109P1D4v.1-DRB1 XLVI -109P1D4v.1-DRBI 0101- 15-mers 0101- 15-mers 0101- 15-mers Each peptide is a portion of SEQ Each peptide is a portion of SEQ Each peptide is a portion of SEQ ID NO: 3; each start position is ID NO: 3; each start position is ID NO: 3; each start position is specified, the length of peptide is specified, the length of peptide is specified, the length of peptide is 15 amino acids, and the end 15 amino acids, and the end 15 amino acids, and the end position for each peptide is the position for each peptide is the position for each peptide is the start position plus fourteen start position plus fourteen start position plus fourteen FW6]1 GTYlFAVLLACVVFH 22 [3231 HKLLVLASDGGLMPA n2o [319]1 ETPNHKLLVLASDGG 18 RFLIEDINDNAPLFP 1121 [3461 V V IRYI 11 VFSNQFLLETAAYLD 18 132lI INDNAPLFPATVINI 425 [ DYESTKEYAIKLLa220 4231 YLDYESTKEYAIKLL 1M -781 LIKSQNIFGLDVIET 2 4591 ENDNAPVFTS F20 [4 I AMLFIKVKDE 118 F251 IETEIEVSIPENAPVG F221 [463] APVFTQSFVT 26411[FYVKAEDGGRVSRSS 1 F328 ILASDGGLMPARAMVL 1121 147011 FVTVSIPENN GGNTRDLFAI 4 021 HEIPFRLRPVFSNQF [2 [522]1 LTWKKLDREKEDKY 20 [750 LVKANDLGQPDSLFS18 F442[ 1GKPPLNQSAMLFIKV 22 [-1-9 DSQTGVIRPNISFDR20 4621 INAPVFTQSFVTVSIP 76811 VNLFVNESVT76L520 [ WIVNLFVNESVTNA 485 ILTKVSAMDADSGPNA 83 NELVRKSTEA 2078 NATLINELVR 18] 502] NYLLGPDAPPEFSLD 22 [883 [ LNFVTIEETADDVD 20 [7] ATLINELVRKSTEAPIM F51o0 PPEFSLDCRTGMLTV g22 F944I PQPAFQIQPE 0F KKKKKKHSPKLL 18 F53] KYLFTILAKDNGVPP 2992] SDCGYPVTTF 2 [918 KYNWVTTPFKSii 157I DNGVPPLTSNVTVFV [2 [63 FKLVYKTGDVPLR19 [986 SDPYSVSDCGYPTT 18] 57 1FVSIIDQNDNSPVFT 22 [6411 KLVYKTGDV 19 [993 DCGYPVTTFEVPVSV 181 DFTIDSQTGVIRPNI1121 [122j LVKIRFLIEII 9 [99 GYPVTTFEVPVSVHT la 1683]1 ELVLPSTNPGTVVFQ 2 f[182]1 QNIFGLDVIETPEGD 19 [697 GTVVFQVIAVDNDTG 22 F32-61 TGLITIKEPLD 1 Table XLVII-IO9PID4v.1 [757 ANDLGQPDSLFSVVI 2352]1 VPSIDI 19 DRBI 0301 - 15-mers 7561 LGQPDSLFSVVVNL 1365]1 NDTVVLSENI Each peptide isa portion of L..11 -SEQ ID NO: 3; each start 75]1 PDSLFSVVIVNLFVN 2 4201 TAAYLDYES 191 position is specified, the length 80011 IADVSSPTSDYVKIL 1 [50 KINYLLGPDAEF of peptide is 15 amino acids, F87 AVGIV--I-gF-41ATSLE g and the and position for each 1~lVAAVAGTITVVVVIF ll [01 A\/TLILDEDDFT 191peptide is the start position plus F9379I YKSASPQPAFQQPE 2 69611 FQVIAVDNDT fourteen 194711 AFQIQPETPLNSKHH 22 r7331 ITLMEKCDVT F10011lFEVPVSVHTRPVG l811 YFAVLLACVVFHSG 181 IGDLLKDLNLL 61 AMQFKLVYKTGDVPL 211 ILACWFHSGA 1 [wII EVAILPDEIF n32 11081 IYEVEVAILPDEIFRL 21 [4I11 IGDLLKDLNLSLIPN 1900]1 GNRVTLDLPIDLEEQ g 18I 1IFGLDVIETPEGDKM 211 [l SLIPNKSLTTAMQFK 18 [36]1 ENVLIGDLLKDLNLS 1 363 IPVNDTVVLSENIPLN 2 j NKSLTTAMQ 1 [7411 LIRIEEDTGEI F29] 54111 LAKDNGVPPLTSNVT 21 [8111 TGEIFTT 1 ZI CAGIPROEHC F 29 7221 IDLFAIDQETGNITLM 2j [33][ NDNAPLFPATVINIS [1251 IRFLIEDiNDNAPLF 291 1431 IVINISIPENSAINSK 1 1i1 APLFPATVIN 502 NYLLGPDAPPEFSLD 291 1IYVMKVKVEDGGFPQR 201 117-01 INGVQNYELIS 893 ADDVDSDGNRVTLDL R2 12221 IEDGGFPQRSSTAILQ 2451 NHPVFKETEIV 365 NDTVVLSENPLNTK E 246 IHPVFKETEIEVSIPE 2571 SIPENAPVGTSVTQL 181 605 VTLSILDENIDFTII 27 1 1l EIEVSIPENAPVGTS] 11o [231 SNIARRLFHLNATTG [3I [671 PVFIVPPSNC;SYEV' I[~i WO 2004/098515 PCT/US2004/013568 197 Table XLVII -109PID4v.1- 1Table XLVII -109P1D4v.1- Table XLVIII - 109PID4v.1 DRBI 0301 -15-mers DRBI 0301 - 15-mers DRBI 0401-15-mers Each peptide is a portion of Each peptide is a portion of Each peptide is a portion of SEQ SEQ ID NO: 3; each start SEQ ID NO: 3; each start ID NO: 3; each start position is position is specified, the length position is specified, the length specified, the length of peptide is of peptide is 15 amino acids, of peptide is 15 amino acids, 15 amino acids, and the end and the end position for each and the end position for each position for each peptide is the peptide is the start position plus peptide is the start position plus start position plus fourteen fourteen fourteen __ __7311 VQNYELIKSQNIFGL [2 [24 TLDLPIDLEEQTMGK 27 288| FSNLVSNIARRLFHL |20 285 HFSFSNLVSNIARRL |28 DLNLSLIPNKSLTTA 6 413| SNQFLLETAAYLDYE| 20 [510 PPEFSLDCRTGMLTV|281 [El NKSLTTAMQFKLVYK 434| IKLLAADAGKPPLNQ ||20 613 NDDFTIDSQTGVIRP 128 13711 SENIPLNTKIALITV 580| PENLPRHGTVGLITV 20 [ 916 MGKYNWVTTPTTFKP g 525 VKKLDREKEDKYLFT 18 696| FQVIAVDNDTGMNAEl 20 F40f IGDLLKDLNLSLIPN |26 613 NDDFTIDSQTGVIRP 26 F1803| VSSPTSDYVKILVA 101 [461 DLNLSLIPNKSLTTA ]|26 [626 RPNISFDREKQESYT 261 1861||NRQMIMMKKKKKKKKI|20 5 4[ 1 NKSLTTAMQFKLVYK 116 [204 QKELDREEKDTYVMK 25 908 PIDLEEQTMGKYNWV|20 1I25]1 IRFLIEDINDNAPLF |26 1275 DADIGENAKIHFSFS 25 928 FKPDSPDLARHYKSA| 20 [167][ DVGINGVQNYELIKS 6 1289 SNLVSNIARRLFHLN 115[ 104 EHCFYEVEVAILPDE |19 354][ SIDIRYIVNPVNDTV ]26 401 DHEIPFRLRPVFSNQ 5 [109 EVEVAILPDEIFRLV |19 5441[ DNGVPPLTSNVTVFV 6 510 PPEFSLDCRTGMLTV 17 DEIFRLVKIRFLIED ||19 TVFVSIIDQNDNSPV1 2 [566 NSPVFTHNEYNFYVP 25 182 QNIFGLDVIETPEGD 19 -04] DTGMNAEVRYSIVGG 268 662 NVVDVNDNKPVFIVP 5 1186 GLDVIETPEGDKMPQ||19 VVIVNLFVNESVTNA 713 YSIVGGNTRDLFAID 1 190 IETPEGDKMPQLIVQ |19 765]1 ATLINELVRKSTEAP k 16 PDEIFRLVKIRFLIE 24 198 MPQLIVQKELDREEK 199]1 NTEIADVSSPTSDYV 2 167 DVGINGVQNYELIKS 24 238 SVTDTNDNHPVFKET 19 F] TVWVIFITAWVRCR [ RVTCFTDHEIPFRLR 2-305 TTGLITIKEPLDREE 19827]1 VIFITAVVRCRQAPH 26 721 RDLFAIDQETGNITL 331 DGGLMPARAMVLVNV 19 83] ADDVDSDGNRVTLDL n(2 325 LLVLASDGGLMPARA 23 415 QFLLETAAYLDYEST 19 963] IQELPLDNTFVACDS | 628 NISFDREKQESYTFY 23 1421 AAYLDYESTKEYAIK 1917 ]I TYIFAVLLACVFHS ||22 946 QPAFQIQPETPLNSK 231 452 LFIKVKDENDNAPVF 16]1 CVVFHSGAQEKNYTl||22 161 PAAVDPDVGINGVQN 22 1518 RTGMLTVVKKLDREK 19 104] EHCFYEVEVAILPDE ||2 488 VSAMDADSGPNAKIN 2 [519 TGMLTVVKKLDREKE 19 1117][ DEIFRLVKIRFLIED 122 925 PTTFKPDSPDLARHY 2 567 SPVFTHNEYNFYVPE 19 [124]I KIRFLIEDINDNAPL ||2I 970 NTFVACDSISKCSSS |22 588 TVGLITVTDPDYGDN [19 297 RRLFHLNATTGLITI ||22 165 DPDVGINGVQNYELl 21 682 YELVLPSTNPGTVVF 19 413 SNQFLLETAAYLDYE ||22 323 HKLLVLASDGGLMPA 211 712 RYSIVGGNTRDLFAI 19 467 TQSFVTVSIPENNSP ||22 405 PFRLRPVFSNQFLLE 21 730 TGNITLMEKCDVTDL 62811 NISFDREKQESYTFY ||22 538 FTILAKDNGVPPLTS 21 746 LHRVLVKANDLGQPD 19 [67011 KPVFIVPPSNCSYEL 22 6981VIAVDNDTGMNAEVR 21 791 EAPVTPNTEIADVSS 19 679 NCSYELVLPSTNPGT ||22 759 PDSLFSVVIVNLFVN ||I 831 TAVVRCRQAPHLKAA 9 721 RDLFAIDQETGNITL 22 [963 IQELPLDNTFVACDS ||21 839APHLKAAQKNKQNSE 768 I VNLFVNESVTNATLI |22 63 FKLVYKTGDVPLIRI 101 1862 RQMIMMKKKKKKKKH 19 8071 TSDYVKILVAAVAGT |22 128 LIEDINDNAPLFPAT ||01 MIMMKKKKKKKKHSP 219 [8]1 LLNFVTIEETKADDV ||22 176 YELIKSQNIFGLDVI ||20 91j KYNWVTTPTTFKPDS |22 WO 2004/098515 PCT/US2004/013568 198 Table XLVIII - 109P1D4v.1- Table XLVIII - 109P1D4v.1- 1 Table XLVIII - 109P1D4v.1 DRB1 0401-15-mers DRB1 0401-15-mers DRBI 0401-15-mers Each peptide is a portion of SEQ Each peptide is a portion of SEQ Each peptide is a portion of SEQ ID NO: 3; each start position is ID NO: 3; each start position is ID NO: 3; each start position is specified, the length of peptide is specified, the length of peptide is specified, the length of peptide is 15 amino acids, and the end 15 amino acids, and the end 15 amino acids, and the end position for each peptide is the position for each peptide is the position for each peptide is the start position plus fourteen start position plus fourteen start position plus fourteen F9 2]PTTFKPDSPDAH [365[ INDTVVLSENIPLNTKI( 20] [7671 IVNLFVNESVTNATL 20 F93] ARHYKSASPQPAFQl j22 [366 I DTWVLSENIPLNTKI jF20] j7691 NLFVNESTALI 1101 F9-6]1 DNTFVACDSISKCSS 7 NTKIALITVTDKDAD 20P 7781[ NATILINEILVIRKSTEA] 2 F9-9]VTTFEVPVSVHTP 379[ KIALITVTDKDADHN E~ 800][j IADVSPTSDVI 2101 -6]j GTYIFAVLLACWVVFHl 20 [393][ NGRVTCFTDHEIPFR IF20 808]1 SDYVKIVAAT P 27][ NYTIREEMPENVI 405][j PFRLRPVFSNQFLLE liol6 81011 YVKILVAAVAGTT F201 [ 36][ ENVLIGDLLKDLNLSj LoiDYT 20 78i] VKILVAAVAGTITVV ]201 37][ NVLIGDLLKDLNS til 7][ TVSIPENNSPGL F201 81 2][ K ILVAAVAGTIlTWV 1101 FL4i1[ GDLLKDLNLSLIPNKl 20i 482[GIQLTKVSAMDADSG 1E 815]1 VAAVAGTITVVI E1o F48 ]I NLSLIPNKSLTTM [2-0] F48-]1VSAMDADSGPNAKIN 20I 819]1 AGTITVVI~FITV L-9-7] CAGIPRDEHC F 0 498]1 NAKINYLLGPDAP F20 181][ TITWVVVIFITAV 20o F1 7ijI EVAILPDEIFR-LVKI- 20 F52-][LTVVKKLDRE Y g~ [8221 ITWVVIFITAVVRC ] F1121 VAILPDEIFRLVI [10 [5341 DKYLIFTILAKDGV 20 [83]9[APHLKAAQKNKQS ~ 1122]1 LVKIRFLIEDINA g [547]I VPPLTSNVTVFVSII [879] KNLLL-NFVIEETKA ]F] 1135]l NAFLFPATVINISIP 1201 F5-5] TSNVTVFVSIIDQN 880][ NLLLNFVTIEETKAD 120 114011 PATVINISIPENSAI] 201558]1 VSIIDQNDNSPVFTH 20 [883JI LNFVTIEETKDV F1431 VINISIPENSAIS 20] F580][ PENLPRHGTVIT 900]1 GNRVTLDLPIDEQ[0 157]1 KYTLPAAVDRDGI 201 60-6]1 TLSILIDENDDFTIDS F 904]1 TLDLPIDLEEQTMGK [20 118111 SQNIGLDVIETPEG201 640]1TFYVKAEDGGRVSR 201 90611 DLPIDLEEQTMKN[o [1 841 1 IFGLDVIETPEDKM 206-48]1[GGRVSRSSSAKVT7IN q I 9471I AFQIQPETPLSH [P0 [2-31]1 STAILQVSVTTD 20 I 658]1 KVTINVVDVNDNP [go [959] KHHIIQELPLDNTFV [10! [232[ TAIILQVSVTIDTNDN 201 6-61]1 INWVDVNDNKPVFIV [20 [9601 HHIIQELPLDNTFVA 20o [234[ ILQVSVTDTNDNP 201 68211 YELVILPSTNPGTVVF 201 [F975]1 CIDSISKCSSSSSPY20 [245J[ NHPVFKETEESI 20 6-9211 GTWFQVIAVDN-DT-G] 201 9-5]1 GYPVTTFEVPVSVHT20! [25-3] EIEVSIPENAVT 2069511 VFQVIAVDNDTGN 201 [121 VLLACVVFHSGAQEK 18 [265]I1 GTSVTQLHATDAI 20 6-9611I IF Q V IA VDNDTGMN AE 20glYj LL VHGQEKN18 [2871[ NAKIHFSFSNLVN F1 698]1 VIAVDNIDTGMNAE-VR] 201[9J FHSGAQEKNYTiREE 1l81 [289][ SNLVSNIARRLF HLN 201 1721RSV TD-LFAI- 201 [51 NSTAQFKL 18 F121KEPLDREETPNHKLL 201 [7-2-0]1 TRDLFAIDQETGI 201 31 PLIRIEEDTGEI1FTT 181 F3-22]NHKLLVLASDG-GLMPg F11 72-311 LFAIDQETGNTM 207811 EEDTGEIFTTGARID IR~ F1 HKLLVLASDGG P X1~ 73811 KCDVTDLGLHRVLVK 201 F-85j[ FTTGARIDREKL-CA-G]i F3371 IDGGLMPARAMVLVN 201 F731 DLGLHRVLVKNL 20 F113]1[ AILPDEIFRLVIF n-i18 F337 ][ARAMVLVNVTDVD [10 [ 7 I[ HRVLVKANDLGQD 20 F1377[ PILFPATVIN ISIPEN 18i~ F33][ RAM VN VTD VND NVI N 753]1 ANDLGQPDSLFSVVI _201 1441 INISIPENSAINSKY Ig~ F3-4][ NDNVPSIDIRYIVNP Lol0 [75911 PDSLFSVVVNL-FVN] 201 148][ IPENSAINSKYTLPA fli 35-7]1 IRYIVNPVNDTL k1o F021 LFSWIVNLFVNE-SV ] 2 1196]1 DKMPQLIVQKELDRE Hi~ N358] RYIVNPVNDTW-VLSE 1oJ [764 SVVVNLFVNESVTN L21 [201][ LIVQKELDREEKDTY II WO 2004/098515 PCT/US2004/013568 199 Table XLVIII - 109P1 D4v.1- Table XLVIII - 109P1 D4v.1- Table XLVIII - 109P1D4v.1- 1 DRBI 0401-15-mers DRB1 0401-15-mers I DRB1 0401-15-mers Each peptide is a portion of SEQ Each peptide is a portion of SEQ Each peptide is a portion of SEQ ID NO: 3; each start position is ID NO: 3; each start position is ID NO: 3; each start position is specified, the length of peptide is specified, the length of peptide is specified, the length of peptide is 15 amino acids, and the end 15 amino acids, and the end 15 amino acids, and the end position for each peptide is the position for each peptide is the position for each peptide is the start position plus fourteen start position plus fourteen start position plus fourteen M20l KVEDGGFPQRSSTAI n18 |7751 SVTNATLINELVRKS |81 6931 TVVFQVIAVDNDTGM|16 F22811 QRSSTAILQVSVTDT 18 7961 PNTEIADVSSPTSDY ||181 EVRYSIVGGNTRDLF 16 [25[ IPENAPVGTSVTQLH 18 813] ILVAAVAGTITVVVV | 18 [z6iDSLFSVVIVNLFVNE ||6! 262 APVGTSVTQLHATDA 1 83311 WRCRQAPHLKAAQK 1 8261 WIFITAVVRCRQAP 16 28211 AKIHFSFSNLVSNIA ][ [8381 QAPHLKAAQKNKQNS 945[ QPAFQIQPETPLNSK 16 29[ ISNIARRLFHLNATTG 854 WATPNPENRQMIMMK 18 iiI NSAINSKYTLPAAVD 15 F298] RLFHLNATTGLITIK 18 1876 HSPKNLLLNFVTIEE |181 953J ETPLNSKHHIlQELP 15 ITIKEPLDREETPNH 890] ETKADDVDSDGNRVT |181 [il MDLLSGTYlFAVLLA |14 F341]1 VLVNVTDVNDNVPSI [[18910711 LPIDLEEQTMGKYNW 18 9] IFAVLLACVVFHSGA |14 TDVNDNVPSIDIRYI 918 929][ KPDSPDLARHYKSAS 18 10 FAVLLACVVFHSGAQ|14 F5]1 DNVPSIDIRYIVNPV [930] PDSPDLARHYKSASP 18 11 AVLLACVVFHSGAQE 1|14 36[ IPVNDTVVLSENIPLN [ll [96[ IIQELPLDNTFVACD II T ACVVFHSGAQEKNYT 1 LSENIPLNTKIALIT H992 SDCGYPVTTFEVPVS 18 ] LKDLNLSLIPNKSLT 1 [38S][VTDKDADHNGRVTCF 18 [io00]1 FEVPVSVHTRPVGIQ [18 [631 FKLVYKTGDVPLIRI |14 [406f FRLRPVFSNQFLLET 18 [2231 DGGFPQRSSTAILQV 17 69 TGDVPLIRIEEDTGE |I14 44IDAGKPPLNQSAMLFI 8 [5] SGTYIFAVLLACVVF 6 71] DVPLIRIEEDTGEIF [q 4-52]1 LFIKVKDENDNAPVF 0 [ ][AMQFKLVYKTGDVPL 16 72 VPLIRIEEDTGEIFT 14 460 NDNAPVFTQSFVTVS][g [64][ KLVYKTGDVPLIRIE 16 [74][ LIRIEEDTGEIFTTG |4 464[ IPVFTQSFVTVSIPEN 82 GEIFTTGARIDREKL 16 GARIDREKLCAGIPR [ 487 IKVSAMDADSGPNAKI 18 [05] HCFYEVEVAILPDEI 116 [107IFYEVEVAILPDEIFR 14 EKEDKYLFTILAKDN 18 11361 APLFPATVINISIPE [16 [109 EVEVAILPDEIFRLV 14 556]1 VFVSIIDQNDNSPVF [f QNIFGLDVIETPEGD 1 116 PDEIFRLVKIRFLIE |H 568 PVFTHNEYNFYVPEN 181 24611 HPVFKETEIEVSIPE 161 1191 IFRLVKIRFLIEDIN ||4| 577 FYVPENLPRHGTVGL 18 [-283]1 KIHFSFSNLVSNIAR 161 [il[ RFLIEDINDNAPLFP 14 [595] TDPDYGDNSAVTLSI 181 3561 DIRYIVNPVNDTVVL 16 [141]1 ATVINISIPENSAIN [ DYGDNSAVTLSILDE [409]1 RPVFSNQFLLETAAY 6145][ NISIPENSAINSKYT ||1 609 ILDENDDFTIDSQTG 420 TAAYLDYESTKEYAI 1 1611 PAAVDPDVGINGVQN 14| 618] IDSQTGVIRPNISFD [[18 [423][ YLDYESTKEYAIKLL 16 [170]I INGVQNYELIKSQNI I14| 625]1 IRPNISFDREKQESY [118 [450 AMLFIKVKDENDNAP F175] NYELIKSQNIFGLDV F4 645AEDGGRVSRSSSAKV 8 463 APVFTQSFVTVSIPE 16 [176[ YELIKSQNIFGLDVI 14 659 VTINVVDVNDNKPVF 18 [53[ KYLFTILAKDNGVPP 16 I8I[ GLDVIETPEGDKMPQ 14[ 689 TNPGTVVFQVIAVDN 18 E55][ VTVFVSIIDQNDNSP 187 LDVIETPEGDKMPQL 740 [ DVTDLGLHRVLVKAN 18 [57 I HNEYNFYVPENLPRH 195 GDKMPQLIVQKELDR 14 [7-50] LVKANDLGQPDSLFS 1-8] [57]1 EYNFYVPENLPRHGT 200][ QLIVQKELDREEKDT 14 LGQPDSLFSVVIVNL 157! I[YNFYVPENLPRHGTV [ F041 QKELDREEKDTYVMK 14 [761] SLFSVVIVNLFVNES 18i 596]1 DPDYGDNSAVTLSIL 213]1 DTYVMKVKVEDGGFP 14| [770[ LFVNESVTNATLINE |18 [639 YTFYVKAEDGGRVSR 16 2I6 VMKVKVEDGGFPQRS| |14 WO 2004/098515 PCTIUS2004/013568 200 Table XLVIII - 109P1D4v.1- Table XLVIIl -1 I9PID4v.1- Table XLIX- 1O9PID4v.1-DRBI DRB1 0401-15-mers DRBI 0401-15-mers 1101-15-mers Each peptide is a portion of SEQ Each peptide is a portion of SEQ Each peptide is a portion of SEQ ID NO: 3; each start position is ID NO: 3; each start position is ID NO: 3; each start position is specified, the length of peptide is specified, the length of peptide is specified, the length of peptide is 15 amino acids, and the end 15 amino acids, and the end 15 amino acids, and the end position for each peptide is the position for each peptide is the position for each peptide is the start position plus fourteen I start position plus fourteen start position plus fourteen 251 ETEIEVS1PENAPVG I 62211 TGVIRPNISFDREKQ ||14 [11611 PDEIFRLVKIRFLIE 25 121 EVSIPENAPVGTSVT 4 [62611 RPNISFDREKQESYT |14 28511 HFSFSNLVSNIARRL F25 26111 NAPVGTSVTQLHATD 14 [656|| SAKVTINVVDVNDNK |14 [0001 TFEVPVSVHTRPVGI 12l 121 FSNLVSNIARRLFHL 1 [6601 TINVVDVNDNKPVFI ||14AMQFKLVYKTGDVPL 14 276I ARRLFHLNATTGLIT 141 166311 VVDVNDNKPVFIVPP ||14! [5181RTGMLTWKKLDREK 129 LFHLNATTGLITIKE 14 [6691 NKPVFIVPPSNCSYE ||14 [ -51TGMLTWKKL 305 ITTGLITIKEPLDREE 14 F6711 PVFIVPPSNCSYELV |14 88211 LLNFVTIEET 13241 IKLLVLASDGGLMPAR 614 [81|| SYELVLPSTNPGTVV [28911 SNLVSNIARRLFHLN 22 325 LLVLASDGGLMPARA 141 16831 ELVLPSTNPGTVVFQ |14 ]QESYTFYVKAEDGGR2! I AMVLVNVTDVNDNVP 14 170811 NAEVRYSIVGGNTRD |14 [i0] TGNITLMEKCDVTD 2 I 3401 IMVLVNVTDVNDNVPS 7131 YSIVGGNTRDLFAID 114 779I ATLINELVRKSTEAP 221 F342]1 LVNVTDVNDNVPSID 14! [730|] TGNITLMEKCDVTDL |141 110021 EVPVSVHTRPVGIQV 22 367I TVVLSENIPLNTKIA 141 7331 ITLMEKCDVTDLGLH |14 11 VLLACVVFHS E 371] ISENIPLNTKIALITV 14 F741|1 VTDLGLHRVLVKAND] 1 371! NVLIGDLLKDLN|LSL4 2 1415] IQFLLETAAYLDYEST 1 773 NESVTNATLINELVR 14342] LVNVDVNDNVPSID 431]1 EYAIKLLAADAGKPP 141 783] NELVRKSTEAPVTPN |14 152211 LTVVKKLDREKEDKY 21 433]I AIKLLAADAGKPPLN 4 824|] VVVVIFITAVVRCRQ I F01 S1DY4ILVAAV 2 4]4 IIKLLAADAGKPLNQ 14 183011 ITAVVRCRQAPHLKA |14 (6]fNRQMMMKKKKKK 1 I 443 IKPPLNQSAMLFIKVK 18!61||NRQMIMMKKKKKKKK ]AVLLACVVFHSGAQE 20 448]1 QSAMLFlKVKDENDN 4 8851 FVTIEETKADDVDSD |14 1821 GEIFTTGARIDREKL 20 453]I FIKVKDENDNAPVFT 14913|EQTMGKYNWVTTPTT l 1[05] HCFYEVEVAI 20 467 INAPVFTQSFVTVSIP 11 919| YNWVTTPTTFKPDSP||14 1-IKDTYVMKVKVE F2 146811 QSFVTVSlPENNSPG 11943!2| SPDLARHYKSASPQP246 GTSVTQLHATDA d 1470 FVTVSIPENNSPGIQ 14 9701| NTFVACDSISKCSSS ||14 F2931 SNIARRLFHLNATTG F4870[SPGQLTKVSAMDAD 14 9881 PYSVSDCGYPVTTFE |144791 NSPGIQLTKVSAMDA20 F02NYLLGPDAPPEFSLD 14 110001 TFEVPVSVHTRPVGI 144821GQLTKVSAM r518RTGMLTVVKKLDREK ! 1002| EVPVSVHTRPVGIQV |141 161!AEDGGRVSRSSK 201 F519TGMLTVVKKLDREKE 14 9321 SPDLAR 20 5I VKKLDREKEDKYLFT 14 Table XLIX - 109PID4v.1-DRB1I 19721 FVACDSISKCSSSSS20 1538 IFTILAKDNGVPPLTS 14 1101-15-mers 11361 APLFPATVINISIPE 19

F

553 INVTVFVSIIDQNDNS 14 Each peptide is a portion of SEQ FI84 1 1 IFGLDVIETP 19 LJL ___ID NO: 3; each start position is J5-8]HGTVGLITVTDPDYG j specified, the length of peptide is 12961! ARRLFHLNAT 58I TVGLITVTDPDYGDN 1[4 15 amino acids, and the end 121INHKLLV position for each peptide is the F L5TVTDPDYGDNSAV - start position plus fourteen 463] APVFTQSFVTVSIPE 19 602 INSAVTLSILDENDDF [- F6601 TINVVDVNDNKPVFI 11 160411AVTLSILDENDDFTI 14 535|| KYLFTILAKDNGVPP |21720 TRDLFADQETGNIT1 160]l LSILDENDDFTlDSQ]114 [827l VFTVRQApH F26] 821 TITVVVVIFITAVVR '[19J WO 2004/098515 PCTIUS2004/013568 201 TableTable XLIX- 109PD4v.1-DRBI Each peptide is a 1101-15-mers F 111M 5Ier 1 101-15-mers portion of SEQ ID Each peptide is a portion of SEQ Each peptide is a portion of SEQ NO: 5; each start ID NO: 3; each start position is ID NO: 3; each start position is position is specified, specified, the length of peptide is specified, the length of peptide is the length of peptide 15 amino acids, and the end 15 amino acids, and the end is 9 amino acids, position for each peptide is the Position for each peptide is the and the end position start poiion plus fourteen 1 start position plus fourteen for each peptide is the start position F-7] TYFAVLLACVVFHS 18 fll IDSQTGVIRPNISFD pui 71[ DVPLIRIEEDTGEIF 18 16791 NCSYELVLPSTN [ STIEICSEI 126 RFLIEDINDNAPLFP 18 8 TNPGTVVFQVI FPTDSRTSTI13 NS75LKYTLP-AAVD-PDVG 18 74- [155j~~~ NSYLMVpV 18[701DTGMNAEVRYSIVGG I MI DSRTSTEI11 182 11QNIFGLDVIETPEGD 18[710_EVRYSVGGNTRDLF E][I-TRPTDSRT [213 [DTYVMKVKVEDGGFP ffal [7381 KCDVTDLGLHRVCVK 16 3 79'[ KIALITV'TDKDADHN 181 768VFVNE TTLI i Table 431] EYAIKLLAADAGKPP 18 F807]1 TSDYVKILVAA18| 16 10 485]LTKVSAMDADSGPNA 18g | 9l[MGKYNWVTTPTF 16] v.20' 498 NAKINYLLGPDAPPE 18 936] ARHYKS QPAFQI 161 Terminal 510-][PPEFSLDCRTGMLTV 18 A0203-9 F5J61HGTVGLITVTDPDYG 18 Table XXII-109P1D4 ____ I69511VFQVAVDNDTGMNA V.2 C'Terminal-Al 9-mere No F601DSLFSVVIVNLFVNE 18 F7-6-411 FSVVIVNLFVN E I- Each peptide is a Results SVVIVNLFVNESVTNportion of SEQ ID Found. LL9ZI[NTEIADVSSPTSDYV [8 NO: 5; each start 9-93]DGPTFV 1 position is specified, TableXXV-1 09P1 D4 t DCGYPVTTFEVPVSVlength of peptide F1f04EHCFYEVEVAILPDE is 9 amino acids, 17'er DEIFRLVKIRFLIED 17 and the end position 1for each peptide is Each peptide is a 210 I EEKDTYVMKVKVEDG 17 the start position Portion of SEQ ID 246 IHPVFKETEEVSIPE 17 plus eight NO: 5; each start F387 [ALTVTDDAD--N-Gposition is specified, 130 IALITV'TDKDADHNG 171 _4_ ALlVKE7N fsl-R T the length of peptide SAMLFIKVKDENDNA is 9 amino acids, and 638 ISYTFYVKAEDGGRVS rl El TT the end position for __ _ __ _ __ _ each peptide is the 670 KPVFIVPPSNCSYEL 1 start position plus 693 TVVFQVIAVDNDTGM 17 1 eight 7 441 LGLHRVLVKANDLGQ 171 1 [819][ AGTITVVVVIFITAV 17 15 F925]1PTTFKPDSPDLARHYF17j TableXXlll F V 1 F]1SDPYSVSDCGYPVTT 109P1D4v.2 C' Terminal-A0201 ~HRTSTE 8LFPATVNSENS 169-mer VQNYELIKSQNIFGL F T 399] FTDHEIPFRLRPVFS I I S T 450 AMLFKVKDENDNAP 16 14 S IECE n I4671 TQSFVTVSIPENNSP 16 50

-

0 ] KINYLLGPDAPPEFS 16v Terinal-2 VTVFVSIIDQNDNSP V- 9-ereia-2 1101-15-mer WO 2004/098515 PCT/US2004/013568 202 Each peptide is a Table XXVIII Each peptide is a portion of SEQ JD 109P1D4v.2 portion of SEQ ID NO: 5; each start C'Terminal-B08 NO: 5; each start position is specified, 9-mers position is specified, the length of peptide Each peptide is a the length of peptide is 9 amino acids, portion of SEQ D is 9 amino acids, and and the end position NO: 5; each start the end position for for each peptide is position is specified, each peptide is the the start position the length of peptide start position plus plus eight is 9 amino acids, eight and the end position 14 STIEICSEI 18 for each peptide is v SRTSTIEIC 1 r SVHTRPTDS_ the start position [~ VTPD plus eight n HRTSI1 E PTDSRTST1 11 F TRPTDSRTS1 12 RTSTIEICS t9H Mj PTDSRTSTI 1 STIEICSEI 12 PVSVHTRPT 1 DSRTSTIEi 1 DSRTSTIEI [ F HTRPTDSRT 10ES RPTDSRTST 1 D OSRTSTEi M [-31 SVHTRPTDS gE PTDSRTSTI E TableXXVII Table XXXI 109P1D4v.2 T X9PID4.2 C'Terminal-B0702 Table XXIX C'Terminal-82709 9-mers Ceil1510- 9-mers Each peptide is a 9-mers Each peptide is a portion of SEQ ID portion of SEQ I0 NO: 5; each start peptide is a NO: 5; each start portontioSEn isosiioeisifeciied position is specified, NO: 5; each start pthont of pepide the length of peptide position is is 9eamino acid is 9 amino acids, specified, the an ends and the end position length of peptide is for e eptii for each peptide is 9 amino acids, and theart postion the start position the end position for psit plus eight each peptide is the start position plus Each peptide is a _______________Ieigh portion of SEQ ID RPTDSRTST 9; each start PVSVHTRPT position is specified, [F] lITRPTDSRT ] VTTSR the length of peptide 10 DRTSTEI ~ ~ i1 VSVHRPTis 9 amino acids, Li---VT7- E and the end position HR HTRPTDSRT for each peptide is Table MXill PTRPTDSRTs]F~ the start position 109P1 14v.2 plus eight -08 Table XXX C' SRTSTIEICi2 9-mers 109P1D4v.2 9- mTRsPTDSRTS Each peptide is a C' Terminal-B2705 ST pEICSE i1 portion of SEQ ID 9-mers NO:c 5; each start NO: 5 e s position is specified, the length of peptide is 9 amino acids, and the end position Table XXXII for each peptide is e p09Pn D4vi2 the start position C'Terminal-B4402 plus eight 9-mers [ac petidisth WO 2004/098515 PCT/US2004/013568 203 Each peptide is a Table XXXV Table XXXVIIi portion of SEQ ID 109P1D4v.2 109P1D4v.2 C' NO: 5; each start C'Terminal-A0201-10- terminal-A26-10-mers position is mers Each peptide is a specified, the Each peptide is a portion of SEQ ID NO: length of peptide is portion of SEQ ID NO: 5; each start position 9 amino acids, and 5; each start position is specified, the length the end position for is specified, the length of peptide is 10 amino each peptide is the of peptide is 10 amino acids, and the end start position plus acids, and the end position for each eight position for each peptide is the start peptide is the start position plus nine STIEICSEI 13 position plus nine HPTDSRTST RTSTIEICSE 13 10 DSRTSTIEl n RPTDSRTSTl SVHTRPTDSR1 10 TDSRTSTIEI DSRTSTIEIC Table XXXIII 13 RTSTIEICSE EH [ ] PVSVHTRPTD1 109P1D4v.2 14 TSTIEICSElI 9HTRPTDSRTS1 C'Terminal-B51 01 E SVHTRPTDSR PTDSRTSTIE Each peptide is a [ HTRPTDSRTS P portion of SEQ ID T TRPTDSRTST Table XXXIX NO: 5; each start V 109PID4v.2 position is specified, C'Terminal-B0702 the length of peptide 10-mers is 9 amino acids, Table Each peptide is a and the end position xxxvi portion of SEQ ID NO: for each peptide is 109PID4v.2 5; each start position the start position C'Terminal- 5; ech t he p ength plu eihtA0203-1 0- is specified, the length plus eight mArs of peptide is 10 amino mers acids, and the end 1 DSRTSTIEI position for each DNoResulits] peptide is the start FI LRPTJDSRTSTF position plus nine PTDSRTSTI 12 1 STIEICSEI 1 Table XXXVi VPVSVHTRPT| 109P1D4v.2 -C' E]1 RPTDSRTSTl 18 Table XXXIV Terminal-A3-10-mers | TDSRTSTIEI j 109P1D4.2 Each peptide is a C' Terminal-A1-10- portion of SEQ ID mers NO: 5; each start Table XL Each peptide is a position is specified, 109P1D4 portion of SEQ ID the length of peptide v.2 NO: 5; each start is 10 amino acids, C'Terminal position is specified, and the end position B08-10 the length of peptide for each peptide is mers is 10 amino acids, the start position plus and the end position nine No for each peptide is Results the start position plus eSHsTRPDSR1 Found. nine SVTPTS 1 7 Fund RJPVSVHTRPTD 1 J PIDSRTSTIE 16 PF RPTDSRTST 12 MPH-IRPTDSRTS1 E HTRPTDSRTS 10 WO 2004/098515 PCTIUS200-/013568 204 Table Table Table LVI-109PlD4v.2 XLI- XLV- C'Terminal-DRBI 0401 109P1D4 109P1D4 15-mers v.2 C' v.2 C' Each peptide is a portion of Terminal- Terminal- SEQ ID NO: 5; each start B1510- B5101- position is specified, the 1 0-mers 10-mers length of peptide is 16 amino LIII III]acids, and the end position for No No each peptIde is the start Results Results position plus fourteen Found. Found. IVTTFEVPVSVHTT I1 Table Table XLVI-109P1 D4v.2 jFEVPVSVHTRPTDSR XLII- C' Terminal-DRBI 0101 I VHTRPTDSRTSTIEI 18 109P1D4 15-mers [ITFEVPVSVHTRPTDS 14 v.2 C' Each peptide is a portion of Terminal- SEQ ID NO: 5; each start 82705-, position is specified, the 10-mers length of peptide is 15 amino If1 HTRPTDSRTS 12 acids, and the end position for No each peptide is the start [FRPTDSRTSTIE Results position plus fourteen Found. Table XLIX-19PID4v.2 Ij TFEVPVSVHTRPTDS 17C'Terminal-DRB 1101 Table SVHTRPTDSRTSTIE 15-mers XLIl~- Each peptide is a portion of 109PI04 [Tj VTFVVHRT 1 SEQ ID NO: 5; each start 1.2 C' VPVSVHTRPTDSRTS 6 position is specified, the Terminal- nii HTRPTDSRTSTIEIC 15 length of peptide is 15 amino B2709- ~ ~ ___________acids, and the end position I 0-mers {jFEVPVSVHTRPTDSRI4 for each peptde is the start V] PVSVHTRPTDSRTST [4 position plus fourteen RPTDSRTSTIEICSE 14 Results EVPVSVHTRPTDSRTjEVPVSVHTRPTDS Found. j VVVTPDR s Table XLV I-109P1D4v.2 jiVTTFEVPVSV-TRPTIH Table XLIV C' Terminal-DRB1 0301 109P1D4v.2 15-mers Table XXII-109P1D4 C' terminal-B4402- Each peptide is a portion of v.2-N'terminal-Al-9 10-mers SEQ ID NO: 5; each start mars Each peptide is a position is specified, the portion of SEQ ID length of peptide is 15 amino Each peptide is a NO: 5; each start acids, and the end position for portion of SEQ ID position is specified, each peptide is the start NO: 5; each start the length of peptide position plus fourteen is 10 amino acids, the length of peptide F - .is 0 amino acids,an and the end position n V H T R P T DiR TaTids,1 7 for each peptide is [i611 VHTRPTDSRTSTIEI F71 the end position for the start position plus EVPVSVHTRPTDSRT 16 each peptide is the nine IIstart position plus mn PVSVHTRPTDSRTST [1 eight 1 T 1TFEVPVSVHTRPTDS TDSRTSTI 1I] VTTFEVPVSVHTRPT 26 1RPTDSRTSTl 11 QiFQVL CGL SEQ IQIEQVL 23 poitio isseiid h WO 2004/098515 PCT/US2004/013568 205 F!] VLCGLIQQT 22 Table XXV-109P1D4 Table XXVI W VLIQIFQV v.2 N' terminal-A3- 109P1D4v.2 N' 9-mers terminal-A26-9-mers GLIQQIVTS 1 Each peptide is a Each peptide is a VTSVPGMDL16 portion of SEQ ID portion of SEQ ID 16 LCGLIQQTV 1 NO: 5; each start NO: 5; each start F2__2 __ F_4]_position is specified, position is specified, QTVTSPGM 1the length of peptide the length of peptide 25 TSVPGMDLL is 9 amino acids, and is 9 amino acids, and RTERQWVLI 1 the end position for the end position for L n3each peptide is the each peptide is the LIQlFQVLC 1 start position plus start position plus eight eight Table XXII-109P1D4 v.2 N' terminal- 18GLIQQTVTS 29GMDLLSGTY 1 A0201________ 9-mers 1 QVLCGLIQQ SVPGMDLLS2 Each peptide is a E VLIQFQVL 1 LMRTERQWVL portion of SEQ ID WVLIQIFQV N NO: 5; each start SVPGMDLLS Table XXVII position is specified, 109P1 D4 the length of peptide 5VLGL!QQT v.2 N' terminal-B0702 is 9 amino acids, and 3TVTSVPGMD 9-mers the end position for I~~ each peptide is the LIFVL Each peptide is a start position plus 29GMDLLSGTY portion of SEQ ID eight REQ LI NO: 5; each start eiTE _LI Qposition is specified, 1QIFQVLGL the length of peptide 19 LIQQTVTSV 2619 LIQQTVTSV El is 9 amino acids, and 11 QIQVLCL 24the end position for QiFQVLeach peptide is the SVLIQIQVL23 Table XXVI start position plus 1 VLCGLIQQT 22 109PID4v.2 N' eight W VLIQIFQV 2 terminal-A26-9-mers _ 1 GLIQQTVTS 9 Each peptide is a ________ 16_ portion of SEQ ID L~ TVGD 16 VTSVPGMDL NO: 5; each startVPGMDLLSG 16 LCGLIQQTV position is specified, 2VLIQFQVL F22] _________H the length of peptide 2QTVTSVPGM1is 9 amino acids, MRTERQWVL 5TSVPGMDLL 14the end position for 2 TSVPGMDLL RTERQWVLI each peptide is the QIFQVLCGL 1 LQ FQVLC start position plus MRTERQWVLI l ] eight_ _ 15 1 VLC G LIQ Q T -l Table QIFQVLCGL 217 CGLIQQTVT E 109P1D4 VTSVPGMDL LIQQTVTSV v.2 N' ]ERQWVLIQ QTVTSVPGM terminal- QVLCGLIQQ [ A0203 H Table XXVIII 9-mers [2 QTVTSVPGMI 109PID4v.2 N' 7 WVLIQ1FQV 1 terminal-B08-9-mers No 23TVTSVPGMD Results 9 VLIQlFQVL 14 Found. TSVPGMDLL|14 [JRQWVLIQIF 1L3 WO 2004/098515 PCT/US2004/013568 206 Each peptide is a Table XXX-109P1D4 Each peptide is a portion of SEQ ID v.2 N' terminal-B2705 portion of SEQ ID NO: 5; each start 9-mers NO: 5; each start position is specified, Each peptide is a position is specified, the length of peptide portion of SEQ ID the length of peptide is 9 amino acids, and NO: ; each start is 9 amino acids, and the end position for NO: 5; .ecfstar the end position for each peptide is the positin is peie each peptide is the start position plus is 9 amino acids, and start position plus eight the end position for eight each peptide is the [ w MRTERQWVL 20 start position plus El VUQFQVL R8 VLIQIFQVL eight TSVPGMDLL 14 1 QIFQVLCGL 14 2MRTRQWL5 ERQWVUQI R 24VTSVPGMDL 2 [ ERQWVL1 __RQWVUF __________ [EjERQWVLI-Q-I -11WVI 3F 2 TSVPGMDLL E RQWVUIQIF Q QFQVLCGL [Table XXIX-09P1D4 $1J QIFQVLCGL |I GMDLLSGTY 13 v2 N' terminal-B1510 El VLIQIFQVL 1 TERQWVU j 9-mers 29 GMDLLSGTY 1 Each peptide is a 21 TSVPGMDLL 4 RTERQWVU 1 portion of SEQ ID RVTSVPGMDL NO: 5; each start MIIFQVLCGU

RI

position is specified, Table XXXI-109P1D4 the length of peptide v.2 N' terminal-B2709 is 9 amino acids, and 9-mers Table XXXIII the end position for Each peptide is a 109P1D4v.2 N' each peptide is the portion of SEQ iD terminal-B5101 start position plus NO: 5; each start 9mers eight position is specified, Each peptide is a the length of peptide portion of SEQ ID is 9 amino acids, and NO: 5; each start 251 FS L 1 the end position for position is specified, SMRTERQWVLL each peptide is the the length of peptide [l VLIQIFQVL start position plus is 9 amino acids, and 2 _VTSVPGMDL13 eight the end position for I VVGDL 13I each peptide is the SQFQVLCGL ____MRTERQWVL start position plus 51 RQWVUQ1F g eight QTVTSVPGM ERQWVIQI 191 SRTERQWVLI 1 E ERQWVUQ Table XXX-109PID4 ElRQWVUIQF 1 LIQQTVTSV 14 v.2 N' terminal-B2705 [] VLIQIFQVL 12 VPGMDLLSG 9-mers 11QFQVLCGL 2 MRTERQWVL1 Each peptide is aTSVPGMDLL 1 IFQVLCGU portion of SEQ ID F WElQFQ 11 16 CGIQV12 NO: 5; each start W F L Q position is specified, QTVTSVPGM1 CGUQQTVT 1 the length of peptide _ is 9 amino acids, and .HRTERQWVU 1 the end position for Table XXXII ,WVUiFQV _ each peptide is the 109PID4v.2 N' start position plus terminal-B4402-9- VUQIFQVL 1 eight mers QFQVLCGL M ___I2 LQTVTSVP E 2PGMDLLSGT El WO 2004/098515 PCT/US2004/013568 207 Table XXXIII Table XXV-109PD4 Table XXXVII 109P1D4v.2 N' v.2-N'terminal-A0201- 1I9PID4v.2 N' terminal-B5101- 1 0-mers terminal-A3 0-mers 9mers Each peptide is a Each peptide is a Each peptide is a portion of SEQ ID NO: portion of SEQ ID NO: portion of SEQ ID 5; each start position 5; each start position NO: 5; each start Is specified, the length is specified, the length position is specified, of peptide is 10 amino of peptide i 10 amino the length of peptide acids, and the end acids, an the end is 9 amino acids, and position for each position for each the end position for peptide is the start peptd i the start each peptide is the position plus nine position plus nine start position plus [ __ :M__I_= p eight W WVLIQI:QVL 116 12 VTSVPGMDL [Q V 2 M G 1 I2~~1 L~~] ~ ~ LIQIFQVLCG ~I IQLGI1 [2JTSVPGMDLL 2 4VSPML i~ GI~VS~~ Table XXXIV 109P1D4v.2- N' terminal-Al-10-mers Table Table XXXVIII Each peptide is a XXXVI- 109PID4v.2 N' portion of SEQ ID NO: 109P1 D4 terminal-A26-1 0-mars 5; each start position v.2-N' Each peptide is a is specified, the length terminal- portion of SEQ ID NO: of peptide is 10 amino A0203 5; each start position is acids, and the end 10-mers specified, the length of position for each liipeptide is 10 amino peptide is the start ads, and the end position fr position for each pu nRults peptide is the start IE position plus nine SRTERQWVLIQ 23 FT - - -DL- STable XXXVII F4]1 ER ________2 STSVPGMDLLS O9PID4.2 N' F E 2 8PGMDLLSGTYerminal-A3--mers 23TvTsvGMDL 22 29GMDLLSGTYI L Each peptide i portion of SEQ ID NO1VGML 71 Table XXXV-1 09P1 D4 5; each start position v.2-N' terminal-A0201- is specified, the length 1 IQIFQVLCGL 10-mers of peptide is 10 amino Each peptide is a acison the end 14QVLCGLIQQT 15 portion of SEQ ID NO: postion fo eah 5; each start position is specified, the length position plus nine E RTERQWVLIQ13 of peptide is 10 amino ________________ acids, and the end 18 position for each peptide is the start Table XXXIX position plus nine V 17 1O9PID4.2N' 14 QVOLQT17 terminal-B07D2-1 Oiner 18 GLIQQTVTSV 29 15 VLCGLIQQTV VLCGLIQQTV 25 1 1 IQIFQLCGL 18 19 LIMQT LSVP 15 l QFQVLCGLI 17 TVTSVPGMDL 2h1 GMDLLGTYI K71 WO 2004/098515 PCT/US2004/013568 208 Each peptide is a Table XLlIl Table XLVI-109P1D4v.2 portion of SEQ ID NO: 109P1D4v.2 N' terminal-DRBI 0101 5; each start position is N' terminal- 15-mers specified, the length of B2709- Each peptide is a portion of peptide is 10 amino 10mer EQ ID e s tart acids, and the end SEQ ID NO: 5; each start position for each position is specified, the length peptide is the start No Result of peptide is 15 amino acids, position plus nine Found. and the end position for each peptide is the start position I plus fourteen 27 VPGMDLLSGT17 Table XLIV FW V Q1_____________ 109PI D4v.2 N'__________ L WVLIQIFQVL 12 terminalB4402-1 Omer [4 ERQWVLIQIFQVLCG|2I VTSVPGMDLL 1 Each peptide is a 10 IQIFQVLCGLIQQTV 26 10 IQIFQVLCGL l portion of SEQ ID NO: n RQWVLIQIFQVLCGL 25 123 VSP MDL1 5; each start position ____________________H TV]____ TSVMDL is specified, the lengthFQVLCGLIQQTVTSV24 6LCGLQQTVT of peptide is 10 amino VLCGLIQQTVTSVPG 23 MRTERQWVLI acids, and the end 16 LCGLQQTVTSVPGM| 23 F311_TERQWVLQ8 p its te sart eacLIQIFQVLCGLIQQT 22 15 VLCGLIQQTV position plus nine 17 CGLlQQTVTSVPGMD||22 18 GLQQTVTSV [ J VLIQIFQVLCGLIQQ |17 2QQTVTSVPGM TERQWVLIQ 21 2GMDLLSGTY r- ERQWVLIQIF 15 Table XLVII-109P1D4v.2 SIQFQVLCGL N' terminal-DRBI 0301 Table WVLIQIFQVL 15mers 109P1D4v.2 Each peptide is a portion of N'terminal-PGMDLLSGTY SEQ ID NO: 5; each start B08-10mers VTSVPGMDLL position is specified, the length Q__ FQVLCGL_ _ 2of peptide is 15 amino acids, and the end position for each Results peptide is the start position Table XLV plus fourteen 109P1D4v.2 Table XLI N' terminal- 5 RQWVLIQFQVLCGL |[2 IO9PIDin.2 10mer 21QQTVTSVPGMDLLSG B1510- | I | QWVLIQIFQVLCGLI |'II 1Omer No Results 13 FQVLCGLlQQTVTSV||17, Found. ~12 IFQVLCGLIQQTVTS 14 No Results 2 GMDLLSGTYFAVLL 1 Found. Table XLVI-I09P1D4v.2 F91 LIQIFQVLCGLIQQT 12 N' terminal -DRB1 0101 TableX~il15.mers 25TSVPGMDLLSGTYIF] |12| Table XLII 15mr 109P1D4v.2 Each peptide is a portion of VPGMDLLSGTYIFAV ||12 N' terminal- SEQ ID NO: 5; each start 2]81 PGMDLLSGTYIFAVL 1 B2705- position is specified, the length 1

Y

1 WVLIQFQVLCGLIQ |fl 10mer of peptide is 15 amino acids, and the end position for each [I LCGLIQQTVTSVPGM I11 peptide is the start position 2I VTSVPGMDLLSGTYI hf No Reultsplus fourteen Found. _______________ VPG____________ E34 Table XLVIII-109P1D4v.2 N' 27| VPGMDLLSGTYFAV||34] terminal-DRB1 0401-15-mers 2]QQTVTSVPGMDLLSG [3] WO 2004/098515 PCT/US2004/013568 209 Each peptide is a portion of Table XXI-109P1D4 Table XXIII-109P1D4 SEQ ID NO: 5; each start v.3-A1-9-mers v.3-A0201-9-mers position is specified, the length Each peptide is a Each peptide is a of peptide is 15 amino acids, portion of SEQ ID NO: portion of SEQ ID NO: and the end position for each 7; each start position is 7; each start position is peptide is the start position specified, the length of specified, the length of plus fourteen peptide is 9 amino peptide is 9 amino ___________________acids, and the end acids and th end 1 FQVLCGLIQQTVTSV 6 position for each position for each achpeptide is the start peptide is the start position plus eight position plus eight [101 IQIFQVLCGLIQQTV 22 6I QWVLlQlFQVLCGLl 20 1 [lTSHGLPLGY 26 74 SLTSTSHGL 23 [9 I LlQIFQVLCGLIQQT 0 SAQASALCY A215ALHHSPPLV 23 n~l QQTVTSVPGMDLLSG 2g 1350 NCTQEChlY 2285 GLCSVDQGV 2 27 VPGMDLLSGTYIFAV 20 SSDGGLGDH RLHPSDDSI 2 Ell TERQWVLQIFQVLC 18 DHDAGSLTS ALCHSPPI 21 14 QVLCGLIQQTVTSVP 18 RTEGDGNSD 1 25 SPLPQIAL [][RQWVLIQIFQVLCGL 14 NSDPESFI 281 QGADGLCSV j1 F] WVLIQIFQVLCGLIQ SFIPGLKK 18 2381SALCYPPL IFQVLCGQQTVTS PLGYPQEEY 1SALCHSPPL 16 LCGLIQQTVTSVPGM 0 DESTFIPG IALCHSPPV 1 117 CGLIQQTVTSVPGMD KSEGKVAGK 214SALHHSPPL P2 GMDLLSGTYlFAVLL SSSDGGLGD 22ALHHSPSA 19 1ASDNCTQEC 15fjHTRPPMKEV 18 Table XLIX-109P1D4v.2 N' SDQGVQGS AAISHSSPL 1 Terminal-DRB1 1101 1 5-mers 294 QHASF 15253SSPPV1 Each peptide is a portion of 302 MSERLHP 267SQAQSVSL 18 SEQ ID NO: 5; each start 31 PSDDSIVI AEITVPTV 17 position is specified, the length PQEEYFORA CLIYGHSDA 1 of peptide is 15 amino acids,F87F40H and the end position for each 145HSDACWMPA 14DACWMEASL peptide is the start position 304 . SERLHPSD 7STQHHPRV plus fourteen 1 MKEVRSCT 1ALCHSEPVT 1 SLDHSSSSQ 5 HLPEGSQES 6 noIIQIFQVLCGLIQQTV] VFQTALC H IGKA I VTSVPGMDLLSGTYI VQTIACH 18 13 FTVPTA 1 I ] RQVLQIQLCG] 1619 8 EALH131 1I24 1VE 61 ER1 LQQWVUTSFVCGD1 5 SLPQVIAL 239ALCYSPLA 16 CGU2QQTVTSVP G SVSQQGWV 1 R9~ LIQIFQVLCGLI-QQT] 14~ __2_72 ____ 16_ U-lFQVLCGUQQT 9 Table XXIll-109P1D4 274 SLQQGWVQG 21 QQTVTSVPGMDLLSG 14 v.3-A0201-9-mers SIKVIPLTT 16 E QWVLIQIFQVLCGUI Each peptide is a KVIPLITFT6] ffII WVLIQIFQVLCGQ 12 portion of SEQ ID NO: KV 1 [1_311 ______________-0 7; each start position is 42]VGS V1 specified, the length of F66]GGHAS1 18 GLIQQTVTSVPGMDL 12 peptide is 9 amino TF1PGLKKA 5_ I27]jVPGMDLLSGTYIFAVF12] acids, and the end FILH A 1 _________________position for each [26-1]V HSA 1 29| GMDLLSGTYIFAVLL 1121 peptide is the start 303TMSERLHPS position plus eight SQRVI

H

WO 2004/098515 PCT/US2004/013568 210 Table XXIII-109P1D4 No Table XXV-109P1D4 v.3-A0201-9-mers Results v.3-A3-9-mers I Each peptide is a Found. Each peptide is a portion of SEQ ID NO: portion of SEQ ID NO: 7; each start position is Table XXV-109P1D4 7; each start position is specified, the length of v.3-A3-9-mers specified, the length of peptide is 9 amino peptide is 9 amino acids, and the end Each peptide is a acids, and the end position for each portion of SEQ ID NO: position for each peptide is the start 7; each start position is peptide is the start position plus eight specified, the length of position plus eight peptide is 9 amino acids, and the end F6. IILGD-HDAGSL 14 position for each 234 SAQASALCY 15 HDAGSLTST peptide is the startSPM SGLPLGYPQE 14 position plus eight GKVAGKSQR 14 109 PESTFIPGL 14 SVHTRPPMK RVTFHLPEG|1 GLKKAAEIT RSCPMK F52 HLPEGSQE| 14 1LIYGHSDAC I []WlHPQpQRK Ii[]GLGDHDAGS [14 1 SLDHSSSSQ LVQTAHH 2 1 GLKKAAEIT 14 14HSPPVTQTI 14161ALHRSQAQS [4 12 EIVQPTVE W4 23ALHRSQAQS 1441KVAGKSQRR 121 16 QAQASALCH 14 28GWVQGADGL 1424SLQQGWVQG 2016 ALCHSPPLS 14 32 DDSIKVPL KVIPLTTFT 0ALCHSPPPI 77 STSHGLPLG KSEGKVAGK 215 ALHHSPPLV 1 1LKKAAEITV 1320QV1ALHRSQ 1929ALCYSPPLA 14 1KAAElIVQP 1337RLHPSDDSI 1922SV.SLQQGWV 1 10AAEITVQPT 1311STFIPGLKK 145KSQRRVEFH 13 1ITVQPTVEE 1310CLIYGHSDA 153HLPEGSQES 13 1SDNCTQECL 1313PLSQASTQH 192FDRATPSNR 13 1SSQAQASAL 13 HS_EVT4 TVQPTVEEA 13 191] ALHS2V 1 ALCHSEPLS PQVSALHH TIALCHSPP 1 205 CHSPPPIQV 1327PLPQVALH 1817PVTQTILC 13 217 HHSPPLVQA GVGSAISQ 1 20 TIALCSPP 3 21 CYSPPLAQA SIKVIPLTT 2 RSQAQSVS13 7PLPQVIALH RPPMKEVVR WVQGADGLC 275 LQQGWVQGA RVTQTIALC 18SVQGQGS1 2SVDQGVQGS 1321PLVQATALH 1738LHPSDDSIK 13 30 HPSDDSIKV 1125PLAQAMAIS 7137VIPLTTFTP 13 F VIPLTTFTP VIALHRSQA 1 7QPRKSGK 6 Table XXVl-1 09P1D4 Tab4 l v-26 -9-mers XXIV-8 GLPLGYPQE 16 Each peptide is a 109P1D4 83PLGYPQEEY 16 portion of SEQ ID NO: v.23-9 14SLDHSSSSQ 16 7; each start position is A0203__9-_QVSA ____SP specfid, the length of 27ALHHSPPSA 16 acids, and the end GKSQRRFTF 1pide i e art 16LYGHSDAC position plus eight WO 2004/098515 PCT/US2004/013568 211 Table XXVI-109P1D4 Table XXVII-109P1D4 EVVRSCTPM2- v.3-A26-9-mers v.3-B30702-9-mers 312 DDSIKVIPL Each peptide is a Each peptide is a portion of SEQ ID NO: portion of SEQ ID NO: 1 DACWMPASL 17 7; each start position is 7; each start position is 316 IKVIPLTTF 1 specified, the length of specified, the length of STFIPGLKK16 peptide is 9 amino peptide is 9 amino acids, and the end acids, and the end [124 TVQPTVEEA position for each position for each 256 SPLPQVIAL peptide is the start peptide is the start 20 QVIALHIRSQ position plus eight position plus eight DSIKVIPLT PESTFIPGL 1jPPMKEVRS 316 KVIPLTTFT 1[1 123 ITVQPTVEE 12 1 RPPMKEVVR14 35DSPEEHP 16 130EESDCT 12 I7 SSGP 4 90 61EYFDR-ATPS9 15 13 HCQGI 211 PLKA 4 229ECLGHSD 12 F9 CHSPPF3 14 21V QVSALHHSP 12 n217 HHSPPLVQA IR 1 PTVEEASDN 1SAQASALCY DDSIKVIPL CTQECLYG 27SVSLQQGWV IPLTTFTPR 14 185GWVQGADGL SQRRVTFHL 288 SVDQGVQGS 1 Table XXVIl-109P1D4 PESTFIPGL 13 2] STTMEWH v.3-B0702-9-mers 229HHSPPSAQA TTMEiWIHP L Each peptide is a F24CYSPPLAQA 27EWHPQPQ | portion of SEQ ID NO: 7; each start position is 250AAISHSSPL 13 ESTFIPGLK2 specified, the length of 267SQAQSSVSL 3 8 PRVTQTIAL peptide is 9 amino F_ ___ QTIALCHSP Q acids, and the end TPRQQARPS position for each HTRPPMKEV 1 PPVTQTIAL 14 peptide is the start 31HPQPQRKSE 12 200QTIALCHSP 14 position plus eight LPEGSQESS 12 (8PPPIQVSAL 11[_______(5LSQESSGL! 250AAISHSSPL PPSAQASAL TTFTPRQQA 142 SPLPQVIAL 2LPLGYPQEE 5VTFHLPEGS 1319 PPVTQTIAL 22(01DPESTFIPG 12 ESSSDGGLG 208 PPPQVSAL 160SSQAQASAL TSTSHGLPL 220 PPLVQATAL SALCHSPPL 7 STSHGLPLG RPSRGDSPM 2 CHSPPLSQA TSHGLPLGY 13TPMKESTTM PRVTQTIAL TVEEASDNC 1 SPRVTQTIA CHSPPPQV |12 131 EASDNCTQE SPPPQVSA SALHHSPPL 284DGLCSVDQG PPLAQAAA SALCYSPPL W SVHTRPPMK SPPLAQAAA 3SHSSPLPQV 1VVRSCTPMK 1230 HPSDDSIKV 1828LPQVIALHR 12 ESTTMElWI 11 SPPLSQAST 1171 [22 _____________r Table XXVIII-109P1D4 39EGKVAGKSQ SPPVTQTIA v.3-B08-9-mers EGSQESSSD 2 219SPPLVQATA fDAGSLTSTS 1 SPPSAQASA WO 2004/098515 PCT/US2004/013568 212 Each peptide is a Table XXVIll-109P1D4 Table XXIX-109P1D4 portion of SEQ ID NO: v.3-B08-9-mers v.3-B1I510-9-mers 7; each start position is Each peptide is a Each peptide is a specified, the length of portion of SEQ ID NO: portion of SEQ ID NO: peptide is 9 amino 7; each start position is 7; each start position is acids, an th end specified, the length of specified, the length of position for each peptide Is 9 amino peptide is 9 amino peptide is the start acids, and the end acids, and the end position plus eight position for each position for each peptide is the start peptide is the start 312 DDSIKVIPL p21 osition plus eight position plus eight 2 56SPLPQVIAL 20I IPGLKKAAE GWVQGADGL 3 QFYTMSERL 12 6SQRRVTFHL 18 [312 DDSIKVIPL I12 SLTSTSHGL Table XXIX-109P1D4 QESSSDGGL]II 2 PPP IQVSAL v.3-B1510-9-mers E][ TSTSHGLPL [I]I Each peptide is a _________ FSri-P-- 220 PPLVQATAL 18 portion of SEQ ID NO: RPPMKEVVR 17 7; each start position is [o-] GNSDPESTF 11 115 PGLKKAAE 17 specified, the length of 4 DACWMPASL I peptide is 9 amino________ 16GLKKAAEIT acids, and the end SSQAQASAL 11 6PPVTQTIAL position for each 66SALCHSPPL 232PPSAQASAL peptide is the start PRVTQTIAL 11 position plus eight __________ 314SIKVIPLTT PPVTQTIAL 33QPQRKSEGK IHPQPQRKS SALHHSPPL 4GKSQRRVTF 217HHSPPLVQA 6 238 SALCYSPPL 11 161SALCHSPPL 11110QHHSPRVTQ 146SQRRVTFHL 10 21]SALHHSPPL CHSPPVTQT LGDDAGSL 281SALCYSPPL ~J25CHSPPPQV 174SLTSTSHGL 10 183SPRVTQTIA CHSPPLSQA 33SDNCTQECL 10 EGKVAGKSQ HHSPRVTQT AAISHSSPL 10 6TPSNRTEGD 14LHHSPPLVQ LHRSQAQSS 47DACWMPASL 22HHSPPSAQA 38 LHPSDDSIK1 20AAISHSSPL SPLPQVIAL IKVIPLTTF 10 262ALHRSQAQ SQAQSSVSL DSPMEEHPL PMKEVVRSC GKSQRRVTF 13 TPMKESTTM 10SSQAQASAL 1109PESTFIPGL 111W VSVHTRPPM 2PPLAQAAAI 1 44GHSDACWMP 11184 LGYPQEEYF jG 267SQAQSSVSL LHHSPPSAQ RPSRGDSPM N PMKESTTME 12 SHSSPLPQVTableXX-109PD4 SDNCTQECL GWVQGADGL v.3-2705-9-mers ALCHSPPPI W VHTRPPMKE Each peptide is a 307RLHPSDDSI FHLPEGSQE 12 portion of SEQ ID NO: 324TPRQQARPS 12 DHDAGSLTS12 7; each start position is F3___5]__E____F specified, the length of 5QRKSEGKVA 158DHSSSSQAQ 1 peptide is 9 amino 37KSEGKVAGK 2 PPPQVSAL acids, and the end PESTFIPGL 220PLVQATAL position for each PRVTQTIALPPSAQASAL_ peptide is the start iI~ PVTQ FA 11 23P QSAL [L21 position plus eight WO 2004/098515 PCT/US2004/013568 213 Table XXX-109P1D4 325PRQQARPSR v.3-B2705-9-mers 184 PRVTQTIAL 21 F-84] IQTAL22 Each peptide is a E 1 184_PRVTQ AL portion of SEQ ID : 6 TRPPMKEV 19 0GKVAGKSQR 7; each start position is 265 HRSQAQSSV SGWVQGADGL specified, the length of RRVTFHLPE 6 1271 F1 peptide is 9 amino 278l HWQAD 1 IWHPQPQR s, and the end [7 SQ 5 1KVAGKSQRR position for each 2 PPVA n 7RPPMKEVVR 17 peptide is the start TSTSHGLPL KSEGKVAGK position plus eight 6SALCHSPPL 44GKSQRRVTF 17GYPQEEYF_____ 24SALHHSPPL fY3 n3 STFIPGLKK FDRA N PPLVQATAL |[A 92] P FDRAPSN 13__________ IKVIPLTTF TQECLYGH SALCYSPPL 1131 48RRVTFHLPE 16 F37]ETLPIALHR 2 AAISHSSPL 13 P-8 F1] 258 [2QIA5R01 9NRTEGDGNS 16DSIKVIPL____ 30QFYTMSERL 13 Fq-1 [ ' 312DDIVP 13 F00 05GNSDPESTF 16 F Q RLHPSDDSI 13 3222F65]QA 13 f___4 ___4]_ 26HRSQAQSSV SRGSPMEE GKSQRRVTF 23SQAQSSVSL E1 V M 6 LGDHDAGSL 9 F2O~1 EW]CTM 12F25]1 30RPSRGDSPM 16PQRKSEGK____ 74SLTSTSHGL 12 1822 MK0] T 15 F_______7_ 993 RT50GN61 TPMKESTTM35QRKSEGKVA 12EDGS 9DRATPSNRT 15ESSSDGGL____ 10IALCHSPPV 12 59 3E] SGG 12 29PPIQVSALH 15GDHDAGSL____ 25GLCSVDQGV 12 [2567 LGDDAGSL 12 20PPLVQATAL 15SHGLPLGY_____ 36ERLHPSDDS 12 2 AAISHSSPL PLGYPQEEY ARPSRGDSP 1 SPLPQVIAL66YPQEEYFDR 12RDSM 27PLPQVIALH 15DNCTQECL____ 35QRKSEGKVA 11 2SQFYTMSER 15131NCTQECLIY 159QESSSDGGL 11Q 30QFYTMSERL 15ACWMPASL__ 84LGYPQEEYF |1 F3001F47 ZAWPS 12 318PLTTFTPR 60SSQAQASAL DRATPSNRT 72]AGSLTSTSH 14 10A GNSDPESTF 1 109PESTFIPGL 14QVSL PESTFPGL 11 15PGLKKAAEl 14 PLVQATALH____ 11 PGLKKAAEl 11 [115 221 PLQTL 127 H_________ 166SALCHSPPL PPSAQASAL AEITVQPTV 173 PLSQASTQH 14 VF 1 YGHSDACWM 11 177ASTQHHSPR 1 LH K SSQAQASAL 1 214SALHHSPPL A14RPSRGP PPVTQTAL 1 238SALCYSPPL 14 PPPQVSAL 11 306ERLHPSDDS 14 Table XXXI-109P1D4 232PPSAQASAL 307RLHPSDDSI 14 v.3-B2709-9-mers 244PPLAQAAAI 333 RGDSPMEEH Each peptide is a 253SHSSPLPQV 11 TRPPMKEVV 1 portion of SEQ ID NO: 267SQAQSSVSL 11 VRSCTPMKE 7; each start positions SATSQFYTM [1-4] specified, the length of 296 23 STTMEWIH peptide is 9 amino 312DDSIKVIPL 29WIHPQPQRK acids, and the end PRQQARPSR ( P_____51 ____ position for each 1 i 5KSQRRVTFH 1 peptide is the start 2SSDGGLGDH position plus eight WO 2004/098515 PCT/US2004/013568 214 Table XXXII1 Each peptide is a Table XXXIII 109P1D4v.3-B4402- portion of SEQ ID NO: 109P1D4v.3-B5101 9-mers 7; each start position is 9-mers Each peptide is a specified, the length of Each peptide is a portion of SEQ ID NO: peptide is 9 amino portion of SEQ ID NO: 7; each start position ads, and the end 7; each start position is is specified, the length position for each specified, the length of of peptide is 9 amino peptide is the start peptide is 9 amino acids, and the end position plus eight acids, and the end position for each position for each peptide is the start PPLAQAAAI peptide is the start position plus eight VAGKSQRRV position plus eight __________ 147DA MPS22 19PESTFIPGL 25CWMPASLKKAAEITV 14 KESTTM_____EW5 1191 IALCHSPPV 162 QAQASALCH 14 SG3G09L HPSDDSlKV F 2 IALCHSPPP 1 5s9 IQ E SS SDGGL 21] 15PGL KKA-A'EI 21 F2_________C__SP___ 256 SPLPQVIAL P19 K2K34 SAQASALCY 1 A5ETVQPTV SPLPQVIAL 21 F1 HSSPLPQVI 114 AAISHSSPL 1220 PPLVQATAL 26o2 IALHRSQAQ14 2501 AASSP 1608 PP - ---AL9F 1 PSDDSIKV 16 PPPQVSAL 2 GADGLCSVD 26MEIWIHPQP 28SALCYSPPL 1932DDSIKVIPL 1 44GKSQRRVTF SALCHSPPL ESTTMEWI3 84PRVTQTIAL 1 PPVTQTIAL 18 114 IPGLKKAAE 13 1PPVTQTIAL 1524SALHHSPPL 1819KAAEITVQP 1 EEYFDRATP 232 PPSAQASAL 1 AAEITVQPT 160SSQAQASAL 14IPLTTFTPR AEITVQPTV 194 HSPPVTQTI 14LPLGYPQEE SPPVTQTA 28PPPQVSAL D14P 22 TALHHSPPS 13 220PPLVQATAL PSDDSIKVI 1 268 QAQSSVSLQ 13 232PPSAQASAL RPPMKEVVR 29SATSQFYTM 24HSSPLPQVI 171DAGSLTSTS 1 30 QFYTMSERL 1 2502AAISHSSPL 16 FH TPRQQARPS 13 1 KERST 13 12 81]Q GLS 161 F3 __24]____ 38]SEGKVAGKS 9 20 MKESTTME12 46 SQRRVTFHL 3 PPMKERS PQRKSEGKV12 781TSHGLPLGY 13 8T LGYPQEEYFI1 LGYPQEEYF 6 LGDHDAGSL 16 NSDPESTF12 88 QEEYFDRAT R AT P TEASDNCTQE 12 105 GNSDPESTF 1314DNCTQECLI '' 11SPPLSQAST 1 NSDPEST17 PPLSQASTQ 15PR]TQTA n106 NSDPESTFI 13- 3________M_ 1EEASDNCTQ 1312HSPRVTQTI 1523ALCHSPPPI 12 3SAQASALCY 94HSPPVTQTI 15SPPQVSA 12 __2 ___34]__ 21 0PLQT 15 ________________] I 246PLQATASH 15 PPQVSALH 311DDSIKVIPL K128LAQVAALH1 LPQVALH Table XXXIV Table XXXII DGLCSVDQG 15 109P1D4v.3-A1 109P1D4v.3-B5101 TRPPMKE 14 10-mers 9-mers LPEGSQESS 14 YPQEEYFDR 14 WO 2004/098515 PCT/US2004/013568 215 Each peptide is a Table XXXV-1 09PI1D4 Table XXXV- 109 P 1D4 portion of SEQ ID NO: Av.3-A201-10-mers U.-A0201-10-mers 7; each start position is Each peptide is a portion Each peptide is a portion specified, the length of of SEQ ID NO: 7; each of SEQ ID NO: 7; each peptide is 10 amino start position is specified, start position is specified, acids, and the end the length of peptide is the length of peptide is position for each peptide 10 amino acids, and the 10 amino acids, and the is the start position plus end position for each end position for each nine peptide is the start peptide is the start _ Jposition plus nine position plus nine 78 STSHGLPLGY29 234 PSAQASALCY 25 6] HTRPPMKEVV [2411 LCYSPPLAQA 135 DNCTQECLY 21 201 PMKESTTMEI 1H 2441 SPPLAQAAI 13 SSDGGLDHD 18 1121 STFIPGLKKA 16 304 TMSERLHPSD 113 101 RTEGDGNSDP 18 [1241 ITVQPIVEEA 161 TTMEIWIHPQ 1 107 NSDPESTFIP 8 SLDHSSSSQA 30 WlHPQPQRKS 2 KEGKVAGKS 17 192ALCHSPVTQ 16 QPQRKSEGKV 2 2SDSIKIPL 7 SDDSIKVIPL 16 I 59 SQESSSDGGL 2 L83LPLGYPQEEY F 74 GSLTSTSHGL 15 1331ASDNCTQECL 2 294 VQGSATQFY142 LlYGHSDACW 15 CTQECIYGH 2 133 ASDNCTQECL 1 16 ASALCHSPPL 5 41CLYGSDAC 168 ALCHSPPLSQ 15 178 ASTQHHSPRV 12 Table XXXV-109P1D4 238 ASALCYSPPL HHSPRVTQTI 12 v.3-A0201-10-mers 31 SIKVIPLTTF 94CHSPPTQTI Each peptide is a portion HLPEGSQESS 14 205LCHSPPQV 12 of SEQ ID NO: 7; each [___ TI [14 start position is specified, DPESTEIPGL LHHSPLVQA the length of peptide is Fl14 FIPGLKKAAE 14SPLPQMIALH 10 amino acids, and the 11 IPGLKKAAEI VIALHSQAQ 12 end position for each peptide is the start 214 VSALHHSPPL 14SSVSLQQGWV position plus nine 264 ALHRSQAQSS 14 27 QGWVQADGL 26 LHRSQAQSSV 12851 DGLCSYDQGV 12 67 GLGDHDAGSL 4 RSQAQSSVSL 14 289 SVDQGYQGSA 2 117 GLKKAAEITV 92 LHPSDDSIKV 14 300 SQFYTMSERL 2 190 TIALCHSPPV 21 335 GDSPMEEHPL 1303 YTMSERLHPS 12 SLQQGWVQGA 2182 GLPLGYPQEE 1308 RLHPSDDSIK 12 142 KVAGKSQRRV 160 SSSQAQASAL 13 HPSDDIKV 12 208 SPPPIQVSAL 19 184 SPRVTQTIAL 13 215 SALHHSPPLV 19 IALCHSPPVT 13 Table XXXVI AAEITVQPTV SPVTQTIAL 109P D4v.3-A0203 147] MDCMPS ___________ 13O-mers SDACWMPASL 204 ALCHSPPPIQ 13 Each peptide is a 250 AAAISHSSPL 18 216 ALHHSEPLVQ 1 portion of SEQ ID NO: 76 LTSTSHGLPL 17 220 SPPLVQATAL 13 7; each start position is 120 IAAEIVQPT]F7 __________ specified, the length of 227 V TALHHSPPSA 13 peptide is 10 amino 203 IALCH-SPPPI 17 228 ALHHSPPSAQ 1 acids, and the end 2531ISHSSPPQ ____________ position for each 2 SLPQV F1 232 SPSAQASAL 13 peptide is the start SSPLPVIAL 239 SALCYSPPLA position plus nine VQGADLCSV 2401 ALCYSPPLAQ 13 I WO 2004/098515 PCT/US2004/013568 216 Table XXVi able XXXV Table XXXVIlH 109P1D4v.3-A0203 109P1D4v.3-A3 109P1 D4v.3-A26 10-mers 1 0-mers 1 0-mers Each peptide is a Each peptide is a portion Each peptide is a portion portion of SEQ ID NO: of SEQ ID NO: 7; each of SEQ ID NO: 7; each 7; each start position is start position is start position is specified, the length of specified, the length of specified, the length of peptide is 10 amino peptide is 10 amino peptide is 10 amino acids and the end acids, and the end acids, and the end position for each position for each peptide position for each peptide peptide is the start is the start position plus is the start position plus position plus nine nine nine 243 YSPPLAQAAA 27 PLPQVIALHR 20 EVVRSCTPMK 113 TFIPGLKKAA 9 68ALCHSPPLSQ DPESTFIPGL 1 242 CYSPPLAQAA 19 273 SVLQQGWVQ9 78 STSHGLPLGY 20 D1571 HSSSSQAQA 18 315 SIKVIPLTTF 19 293 GVQGSATSQF 20 159 SSSSQAQASA 18 137 I RKSEGKVAGK 18 105 DGNSDPESTF 219HPPLVQATA 18 1228 ALHHSPPSAQ 18 135 DNCTQECLIY 119 L2291 LHSPPSAQA 181 12401 ALCYSPPLAQ 18 76 LTSTSHGLPL 18 231HSPPSAOASA R 280WVQGAGLCS18 STFIPGLKKA 18 241 LCYSPPLAQA AGSQRRVTF7 315 SIKVIPLTTF 18 FPGLK E GLGDHDAGSL 7 EYFDRATPSN 16 SPPLAQAAAI LYGHSDACW 7 124ITVQPTVEEA 16 155 SLDHSSSSQA 17 208 SPPPQVSAL 6 Table XXXVII 213 QVSALHHSPP 17 2 QVIALHRSQA 6 109PID4v.3-A3 ElWlHEQPQR KVIPLTTFTP 16 1 0-mers 10-mrs IW1HPQPQRK ESTTMEIWIH 15 Each peptide is a portion 2 KVAGKRRV 16TTMEWHPQ 1 of SEQ ID NO: 7; each start position is 111 ESTFIPGLKK 16 EIWIHPQPQR 1 specified, the length of TRPPMKEVR 1EITVQPTVEE 15 peptide is 10 amino I]1 acids, and the end VVRSCTP MKE 1256 SSPLPQVIAL 15 position for each peptide RVFHLPEGS SDDSIKVIPL 15 is the start position plus 7 GLKKAAEITV 1VTFHLPEGSQ nine F-71GK4~T 5E - FLE Q[ -1 252 AISHSSPLPQ 1 11ESTFIPGLKK 1 308 RLHPSDDSIK 30 26GLSVDQGVQ 128 PTVEEASDNC 14 EVRSCPMK 24 CTQECLlYGH 114 RQTILCH 4 Table XXXVIII 223 LVQATALHHS 8 109PID4v.3-A26 314 DSIKVIPLTT 14 261 QVIALHRSQA 24 10-mers 322 TTFTPRQQAR KVIPLTFTP 3 Each peptide is a portion 13 192 ALCHSPPVTQ of SEQ ID NO: 7; each ESSSDGGLGD 293 GVQGSATSQF 22 start position is 0 DHDAGSLTST 13 specified, the length TVQPTVEEAS 13 216 AHSPLQ 2 peptide is 10 amino 264 ALHRSHASS 21 acids, and the end 29 TVEEASDNCT AL8RVQAQS position for each peptide 189 QTIALCHSPP 13 P 8 is the start position plus 201 QTIALCHSPP 13 222 PLQASH nine I246 PLQAS 029 SD QGA 1 WO 2004/098515 PCT/US2004/013568 217 Table XXXVIII Table XXXIX 1Table XILII' I 09P1 D4v.3-A26 1 09P1 D4v.3-B07O2 I 09P1 D4v.3 1 0-mers 1 0-mers jB2705 1 0-mers Each peptide is a portion Each peptide is a of SEQ ID NO: 7; each portion of SEQ INi start position is 7; each start position is [o Results specified, the length of specified, the length of Found. peptide i 10 amino peptide is 10 amino acids, and the end acids, end the end position for each peptide position for each peptide Table XLIII is the start position plus is the start position plus 109P1 D4v.3 nine nine B2709 [ ___ 11 0-mers 300 SQFYTMSERL 13 F335IGDSPMEEHPL 14N 33YTMSERLHPS 17 PME S 13 133 ASDNCTQECL 13 Table XXXIX 1160FSSSQAASAL 13 Table XLIV-109P1D4 109P1D4v.3-B0702 VSALHHSPPL I13 v.3-B4402-10-mers 1beI0-mers 10mes3121 SDDSIKVIPL 13 Each peptide is a portion Each peptide is a portion of SEQ IN 319 IPLTTFTPRQ 13 of SEQ ID NO: 7; each Start position is specified, 7; each start position is W FVPV SVHTRPP 12 the length of peptide is specified, the length of peptide is 10 amino acids, and the end 55 LpEGSQESSS 12 eption fo each position for each peptide 83 LPLGYPQEEY 12 peptide is e is the start position plus nine ____ 1 1 1 1 1147 SAWPL12.2 KESTTMIW 2 184 SPRVTQTIAL 210 PPIQVSALHH 12 AEITVQPTVE 119 208 SPPPIQVSAL [4 i21 PPLVQATALH 119 208 SPPPIQVSAL 18 1 SPPVTQTIAL 425 PPLAQAAAIS 2 256 SSPLPQVIAL 220 SPPLVQATAL 2256 SSPLPQVIAL AGKSQRRVTF 16 109 DPESTFIPGL 21 257 SLQI H 12 96 SPPVTQTIAL 16 232 SPPSAQASAL SPPLVQATAL 16 115 IPGLKKAAEI Table XL 310 HPSDDSIKVI 16 310 HPSDDSIKVI D I9OB 1331ASDNCTECL 15 244 SPPLAQAAAI J I 0-mers 160 sSSQAQASAL 15 87 YPQEEYFDRAI 1 L l l84/ SPRTQTIAL 15 4 QPQRKSEGKV232 SPPSAQASAL 15 76 LTSTSHGLPL Fu 335 GDSPMEEHPL 1 166 ASALCHSPPL 27 MEIWIHPQPQ 238 ASALCYSPPL D4v.3- 14 W RPPMKEVVRS 1 B1510 110 ESTF 19 TPMKESTTME 14 10-mers 166 ASALCHSPPL 4 233 PPSAQASALC 14 250 AAISHSSPL 14 No Results 194 CHSPPVTQTI 1 267 RSQAQSSVSL 14 Found. 238 ASALCYSPPL 14 325 TPRQQARPSR 14 SPPLAQAAAI 14[ IP-SRGDME 1 1201m j14 WO 2004/098515 PCT/US2004/013568 218 Table XLIV-109P1 D4 Table Table XLVI-1 09P1D4v.3 v.3-B4402-10-mers XLV-0101-15-mers Each peptide is a portion 109P1D4 Each peptide is a portion o SEQ of SEQidNO;eac v.3- ID NO: 7; each start position is of SEQ ID NO: 7; each B501 start position is specified, B5101 specified, the length of pepde is the length of peptide is I0-mers 15 amino acids, and the end 10 amino acids, and the position for each peptide is the end position for each .

start position plu fourteen peptide is the start Results position plus nine Found. RVTFHLPEGSQESSS F_ 27011 LHRSQAQSSVS-LQ-QGT 20 3 SEGKVAGKSQ 13 Table XLVI-109P1D4v.3- STTMEIWIHPQPQRK 19 46 1 KSQRRVTFHL _ DRB1 0101-15-mers 74 GSLTSTSHGL 13 Each peptide is a portion of SEQ ID NO: 7; each start position is 120 IPGLIKAAEITVQP19 - LTSTSHGLPL specified, the length of peptide is 3 LTTFTPRQQA EEYFDRATPS 13 15 amino acids, and the end __________________ L18 109 DPESTFIPGL 13 post ion e peptide is the 131 EEASDNCTQE 13 SVSLQQGWVQ1L 12501 AAAISHSSPL 13KV127TFTPRQ 293 VQGSTSQFEl 32011 SIKVIPLTTFTPRQQ Fol 291 GLCSVDQGVQAT 18~ F2 1GVQGSATSQF 1 QRVTHPESE 300 SQFYTMSERL I 531 fl QRRVTFHL PEGSQES 26i 3321 RQQARPSRGDSPMEE 181 315 SIKVIPLTTF 311461 LIYGHSDACWMPAS 26 TFEVPVSVHT 17 SIV2P45LT ALCYSPPLAQAAAIS 26 171 KEVVRSCTPMKESTT 17 60l QESSSDGGLG l _g 281 LQ1VGAGCV251 I 211 RSCTPIMKESTTMEIWI 17 67 Q [ DG 2 QQGWVQGADGLCSV_1 83GLLGDHAGE El WIHPQPQRKSEGK 1241 QRKSEGKVAG F7 89 QEEY DGGLGDHDAGSLTST 124 42 RKSEGKVAGKSQRRV 17 P-QEEYF:DRATPg P QVSALHHSPPLVQS DNCTQECLlY 12161 PQVALHHSPPLVQ L241 QRRVTFH17 223 HHSPPLVQ AALHH-S 24 67 SSSDGGLGDHDAGSLI 17 [139FQ-EC=LIYGHSD 12___________ ____________ 17_ 264ELPQVIALHRSQAQSS 24 78 AGSLSTSH 147 SDACWMPASL 12 F VIALHRSQAQSSVSL 24 114 DPETFIPGLKKAAE 17 PSAQASALCY 283QGWVQGADGLCSVDQ 141 118 TFIPGLKKAAEITVQ 17 2 SHSSPLPQVI 318 DDSIKVIPLTTFTPR [ 24 189 SPRVTQTIALCHSPP I 306 SERLHPSDDS 3 CTPMKESTTMEWH 3 12 KEWRSCTPM 11 11931 TQTIALCHSPPVTQT 23 225 SPPLVQATALHHSPP 117 SQESSSDGGL 05 TQTIALCHSPPPIQV 23 228 LVQATALHHSPPSAQ 17 11 TEGDGNSDPE 1 12761 QSSVSLQQGWVQGAD2247 CysPPLAQAAAISHS 17 DGND3P27 E TTFTPRQQARPSRGD 23 25 L 1 VEEASDNCTQ I I FEVPVSVHTRPPMKE 2 275 AQSSVSLQQ 17 8 LHSDACW PQPQRKSEGKVAGKS 22 304 TSQTMSERLHPSO 17 V____SALHSPL 111PASLDHSSSSQAQAS 22 309 TMSERLHPSDDSIKV 17 27Q1QSSVSLQQGW 11 1248 YSPPLAQAAAISHSS 22 W VTTFEVPVSVHTRPP 16 276 S QGW611 SSPLPQVIALHRSQA 22 ADGL 12961 DQGVQGSATSQFYTM 2 32 M 16 ERLHPD12S6 AAEITVQPTVEEASD 21 GKSQRRVTFHLPEGS 16 294 SVDQGVQGSATSQFY 21 57 TFHLPESQESSSDG 16 305 SQFYTMSERLHPSDD 21 77 DAGSLTSTSHGLPLG 16 E 20P 79 GSLTSTSHGLPL2YP 0 1 6 WO 2004/098515 PCT/US2004/013568 219 Table XLVI-109P1 D40- Table XLVI-109P1 D4v.3- Table XLVII-109PID4v.3 DRB1 0101-15-mers DRB1 0101-15-mers DRBI 0301 15-mers Each peptide is a porion of SEQ Ec Each peptide is a portion of SEQ EcpetdisaoronfSQEchpeptide is a portion of ID NO: 7; each start position is ID NO: 7; each start position is SEQ ID NO: 7; each start specified the length of peptide is specified, the length of peptide is position is specified, the length 15 amino acids, and the end 15 amino acids, and the end of peptide is 15 amino acids, position for each peptide is the position for each peptide is the and the end position for each start position plus fourteen start position plus fourteen peptide is the start position plus I____________ I fourteen [21 TSTSHGLPLGYPQEE 116 1 ECi S 1120 I I GLPLGYPQEEYFDRA 16 1156 WMPASLDHSSSSQAO 11-I 120 AQT F9-4[ QEEYFDRATPSNRTE 116 AQASALCHSPP=LSQA 15 21 I9-5]1EEYFDRATPSNRTEG I6 1811SQASTQHHSPRVTQT 1 29 [109 GDGNSDPESTFIPGL 1861 QHHSPRVTQTIALCH 15 F LTTFTPRQQRPSRG 1 STFIPGLKKAAEITV LCHSPPVTQTIALCH 15 128 EITVQPTVEEASDNC 6212 HSPPPIQVSALHHSP 151SQ 141 NCTQECLIYGHSDAC 16 IQVSALHHSPPLVQA 5304 TSQFYTMSER S 16 11541 ACWMPASLDHSSSSQ 16 229 VQATALHHSPPSAQA 78 AGSLTSTSHGLPLGY IM 155 CWMPASLDHSSSSQA 16 2 AQASALCYSPPLAQAE 15 Fl3 EEASDNCTQECLIYG 161 LDHSSSSQAQASALC 16 2651 PQVIALHRSQAQSSV 15 17 KEWRSCTPMKESTT 13 11631 HSSSSQAQASALCHS 1 51 _E SSDG OLGDHDA 13 1168 QAQASALCHSPPLSQ 1e-j F2 I TVDGLGDH ASS 13 18711 HHSPRVTQTIALCHS T16 X 91 E E 1191 TQIACHPPTQ 16DRB1 0301 15-mers [ 132 QPTVEEASDNCTQEC] 13 11921 VTQTIALCHSPPVTQ p t l~ VQTALHSPPQ 61Each peptide is a portion of 243 ASALCYSPPLAQMAA 131 204 VTQTIALCHSPPPlQQl0 s SEQ ID NO: 7; each start 125 QIALH RSQAQSSV Ut3] 214 PPPIQVSALHHSPPL 16 position is specified, the length LHHSPPLVQATALHH of peptide is 15 amino acids, F221 HSPLOAAHH16and the end position for each Table XLIX-1 09PI D4v.3 226 PPLVQATALHHSPPS 16 peptide is the start position plus ORBI 1101-15-mers 233 ALHHSPPSAQASALC [161 fourteen Each peptide is a portion of SEQ 235 HHSPPSAQASALCYS 16 ID NO: 7; each start position is 240 SAQASALCYSPPLAQ 08 EGDGNSDPESTFIPG 2 Speced, the length of peptide is 19 15 amino acids, and the end 246 LCYSPPLAQAAAISH 8Q-EEYFDRA 4 position for each peptide is the 2491 SPPLAQAAAISHSSP 16 DDSIKVIPLTTFTPR Ij start position plus fourteen 258 ISHSSPLPQVIALHR 6 268 ALHRSQAQSSVSLQ 16 STFIPGLK 19 E rRPPMKEVVRSCTPMK F61 2921 LCSVDQGVQG SATSQ 161 13 RPPMKEVVSTM 18 264 LPQVALHRSQAQSS 161 LCVQVGSTS 1D 8F-9 DGCVQV A2 300 QGSATSQFYTMSERL 6 Ef TFHLPEGSQESS 1 2 A 2 VIPLTTFTPRQQARP 1 I0 DGGLGDHDAGS 1 PI VTTFEVPVSVHTRPP 22 W PVSVHTRPPMKEVVR 5 18 153 DACWMPASLDHSSSS F131 RPPMKEVVRSCTPMK 1 128 ETVQPTVEE 18 5 EVPVSVHTRPPMKEV 20 11 MKEVVRSCTPMKEST 1 296 DQGVQGSATSQFYTM 18 16 MKERSCTPM 47][ KVAGKSQRRVTFHLP 15 31 TMEIWIHPQPQRKSE [23] CTPMKESTTMEIWIH 20 F5-6] VTFHLPEGSQESS 15 45 FEG-KVAGKQRRVTFHj 17 Eflj EIWIHPQPQRKSEGK gVo HPGSQSS KVAGSRRVTFHLP TFHLPEGSQESSSDG 120 F721GLGDHDAGSLTSTS-HH ff 17511 DHDAGSLTSTSHGLP I 86 HGLPLGYPQEEYFDR 17 120 IPGLKKAAEITVQPT 1201 85ll SHGLPLGYPQEEYFIJ F15, MA0 SNTGGSPETF]132 QPTVEEASDNCTQ F( 20 WO 2004/098515 PCT/US2004/013568 220 Table XLIX-1 09P1 D4v.3 Table XLI-09P1 D4.3 Each peptide is a DRB1 1101-15-mersof SEQ ID DR13 111-1-mes DB1 101-6- ~rS-1 1NO: 9; each start Each peptide is a portion of SEQ Each peptide is a portion of SEQ position is ID NO: 7; each start position is D NO: 7; each start position is specified, the specified, the length of peptide is specified, the length of peptide is length of peptide is 15 amino acids, and the end 15 amino acids, and the end 9 amino acids, and position for each peptide is the position for each peptide is the the end position for start position plus fourteen start position plus fourteen each pepide is the I start position plus j)5 PSLDSSSQAQS 21 5-3] QRRVTFHLPEGSQES 1141 eight F- 1PASLDHSSSSQAQAS n ST 1 F17 7 SPPLSQASTQHHSPR [20] [GG HLTST 14 n2 WHPQP =-Q [ Q 193 TQTIALCHSPPVTQT 20 7 Sl 216 PlQVSALHHSPPLVQ 201 117 STFIPGLKKAAEITV H Q 2651 PQVIALHRSQAQSSV 20 1261 MEITVQPTV 14 283 QGWVQGADGLCSVDQ EITVQPTVEEASDNC 14 292 LCSVDQGVQGSATSQ 20 144 QECLIYGHSDACWMP 11al Table .. II 3 SIKVIPLTTFTPRQQ 4-A2 323 VIPLTTFTPRQQARP 20 17hJ ASALCHSPPLSQAST 1 9-mers 56 VTFHLPEGSQESSSD 1 195 TIALCHSPPVTQTIA Each peptide is a flj GLGDHDAGSLTSTSH 18 205 TQTIALHSPPPIQV 4 portion of SEQ ID NO: 9; each start 155 CWMPASLDHSSSSQA 8207 TIAL 14 position is specified, 16 WMPASLDHSSSSQAQ 18 21 PPPI 14 the length of peptide _ _ 9 -is 9 amino acids, 174 LGHSPPLSQASTQHH 1219 VSAL Q 1 and the end position 86 QHHSPRVTQTIALCH 225 SPPLVQATALHHSPP 14 198 LCHSPPVTQTIALCH 81 1226 PPLVQATALHHSPPS the start position 222 LHHSPPLVQATALHH 8 231 ATALHHSPPSAQASA JL plus eight LCYSPPLAQAAAPLAISHA 2461 LCYSPPLAQAMAISH 18L 243 ASLYPLQA 141 ______ 251 PLAQAAAISHSSPLP 2491 SPPLAQAAAISHSSP 1 IPQPQSQ 1 SISHSSPLPQVIALHR 8 255 AAAISHSSPLPQVIA 1141 263 PLPQVIALHRSQAQS 8 2611 SSPLPQVIAL 4 269 ALHRSQAQSSVSLQQ 118 2671 VIALHRSQASSVSL 275 AQSSVSLQQGWVQGA 276 QSSVSLQQGWVQGAD 109P1 D4v4 286 VQGADGLCSVDQGVQ 278 SVSLQGWVQGADGL H 3121 ERLHPSDDSIKVIPL 18 296 DQGVQGSATSQFYTM 4 9-mers F4] QEEYFDRATPSNRTE D17 SERLHPSDDSIKVIP 14 F32 MEIWIHPQPQRKSEG 16 DDSIKVIPLTFTP 41 oud. 89 PLGYPQEEYFDRATP 16 EEYFDRATPSNRTEG 16 Table XXII IIET1 09P1 D4v.4-A1 0P 6 Ill61 ESTFIPGLKKAAElT16 109P1D4v.4 11461 CLlYGHSDACWMPAS 6 3-9-mers 245 ALCYSPPLAQAAAIS 16 3051 SQFYTMSERLHPSDD 161 45 EGKVAGKSQRRVTFH F] 7] TFEVPVSVHTRPPMK 14 STTMEIWIHPQPQRK 14 D 1 1 st TMEIWIHPQPQRKSER 0 et

S

WO 2004/098515 PCT/US2004/013568 221 Each peptide is a Table XXVIII Table X)OI portion of SEQ ID 109P1D4v.4-B08 109P1D4v.4 NO: 9; each start 9-mers B2709-9-mers position is specified, Each peptide is a Each peptide is a the length of portion of SEQ ID portion of SEQ ID peptide is 9 amino NO: 9; each start NO: 9; each start acids, and the end position is specified, position is osition sfed thei poiinfor each the length of peptide leghspetie the peptide is the start is 9 amino acids, e s position plus eight ,and the end position 9 amino acids, and or each peptide is the end position for W PQ~QRRVTF 15 the start position each peptide is the p tFdeplus eight start position plus jJWIHPQ.PSQ 1 ______ eight 1IHPQPQSQR 12 PQSQRRVTF ~Z Iiiii SQSQRRVTFH 12 QSQRRVTFH & j PQPQSQRRV ~ ___PQ.QS__HQPQQRR PQSQRRVTF ~ ~] I1HP~QS "' ~JHPQPSQRR[] ~IWiHPQPQS Table XXVI Table XXIX 1 09P1D4v.4-A26 1 09P1 D4v.4 'Table XXXII 9-mers B1510-9-mers 109P1D4v.4 Each peptide is a Each peptide is a ,B4402-9-mers portion of SEQ ID .portion of SEQ ID Each peptide is a NO: 9; each start NO: 9; each start portion of SEQ ID position is position is specified, NO: 9; each start specified, the. the length of position is specified, length of peptide is peptide is 9 amino the length of 9 amino acids, and acids, and the end peptide is 9 amino the end position position for each acids, and the end for each peptide is peptide is the start position for each tinplus eight peptide is the start plus eight position plus eight PQSQRRVTF IHPQPQSQR| 1 g PQSQRRV WIHPQPQSQ PQSQRRVTFPQSQRRVTF IWlHPQPQS Table XXX 109P1D4v.4-B2705 Table XXXIII Table XXVII 9-mers 109P1D4v.4-B5101 109P1D4v.4-B0702 .Ec9-mers portion of SEQ ID Each peptide is a Each peptide is a NO: 9; each start portion of SEQ ID portion ofSQID position is specified, NO: 9; each start NO: 9; each start the length of peptide theitin f speie position is specified, is 9 amino acids,thleghopptd the length of peptide and the end position is 9 amino acids, is 9 amino acids, for each peptide is and the end position and the end position the start position for each peptide is fo ahpeptide is plus eight the start position for~ eac plseih the start position mo_ eI plus eight IHPQPQSQR ________ ]HPQPQSQRR 14PSQRT HQPQSQRRT PQPQSQRRV HQPQSQRR 18SQRVT HPQPQSQRR 1 jPQSQRRVTF 11~QSQRRVTFH 11 WO 2004/098515 PCT/US2004/013568 222 Table XXXIV Each peptide is a Table 109P1D4v.4-A1 portion of SEQ ID

XL

10-mers NO: 9; each start 109P1D4 position is specified, v.4-B08 Each peptide is a the length of peptide 10-mers portion of SEQ ID is 10 amino acids, NO: 9; each start and the end position No position is specified, for each peptide is the length of peptide the start position plus Results is 10 amino acids, nine Found. and the end position for each peptide is L__Table____ the start position WHPQPQSQR 109P Dv4 plus nine _-i m 1 09P1 D4v.4 plusnine _ VQPQSQRRVTF B1 510 EIWlHPQPQS12 10-mers P3 WIHPQPQSQR E HEQPQSRRV4 Table XXXVIII Results QSQRRVTFHL 109P1D4v.4-A26 Found. SPPQS:RVT n2 I 0-mers Each peptide is a Table XLII Table XXportion of SEQ ID 109P1D4v.4 Table XXXV NO: 9; each start B2705 109P1D4v.4-A0201 position is specified, 10-mers 10-mers the length of peptide Each peptide is a is 10 amino acids, portion of SEQ ID NO: and the end position No Results 9; each start position for each peptide is Found. is specified, the length the start position plus of peptide is 10 amino nine acids, and the end Table XLIII position for each L ~ ~ i1O9PID4v.4 peptide is the start NJ EIWIHPQPQS 15 B2709 position plus nine QPQSQRRVTF10 10-mers EQSQRRVTFHL 8 E HPQPQSQRRV 1 qj WIHPQPQSQR No[uits n WIHPQPQSQR 10 QSQRRVTFHL 10Table XXXIX Table XLIV EIWIHQPQS 7 109P1D4v.4-B0702 109PID4v.4-B4402 ~ IWHP~QSQ [~jI 0-mars 1 0-mars Each peptide is a - es portion of SEQ ID NO: Each peptide is a T a-blI e -XXXV 1 9; each start position NO 9 of sQrI 109P1D4v.4- is specified, the length position is specified, A0203 of peptide is 10 amino the length of peptide 10-mers acids, and the end is 10 amino acids, position for each and the end position peptide is the start for each peptide is position plus nine the start position plus Found. nin nine Table XXXVII ~ QPQSQRRVTF 19 109P1D4v.4 HPQPQSQRRV QPQSQRRVTF A3-10-mers QSQRRVTFHL

QSQRRVTFHL

WO 2004/098515 PCT/US2004/013568 223 Table XLV Each peptide is a 109P1D4v.4- j 7 RR portion of SEQ ID H50 FT________________ NO: 11; each start B5101V 10-mers 1]MEIWIHPQPQSQRR 1 position is specified, Z uluOP0 OILTMIWHQP the length of 161 EIWIHP-QPQSQV 4j~ peptide is 9 amino llHPP 14 ~ acids, and the end No ResultsESTTMEIWIHPQQS 12 position for each 3] TMEIWHPQQSQRF21peptide is the start Table XLVI-109P1D4v.4 IWIHPQPQSQRRVTFH1p i l g DRBI 0101-15-mers Each peptide is a portion of 16 SEQ ID NO: 9; each start SVHTRPSQR position is specified, the length DRB'0lIl4mer of peptide is 15 amino acids, and the end position for each Each peptide is a portion of 09PI D4v.5 peptide is the start position SEQ ID NO: 9; each start A0203-9 plus fourteen position is specified, the mers length of peptide is 15 amino 7 STTMEIWIHPQPQSQ 19 acids, and the end position for L~~~~I each peptide is the start N eut 4 jTMElWIHPQPQSQRR 19 position plus fourteen MEWIHPQPQSQRRV 16 13PQSQRRVTFHLPEGS 6 STTMEIWIHPQPQSQ] Table XXV n WIHPQPQSQRRVTFH 5 13 PQSQRRVTFHLPEGS 13 9 -A3 F6] EIWIHPQPQSQRRVT 14IlTMEIWIHPQPQSQRR] 12 9mr EVEach peptide is 10HPQPQSQRRVTFHLP 1 Eli1 portion of SEQ ID 12QPQSQRRVTFHLPEG 1 j IHPQPQSQRRVFHL 10 NO: 11; each start ~1 TMEIIHPQQSQ position is specified, the length of Table XXI I peptide is 9 amino Table XLVII-109P1 D4v.4 109P1D4v.5A1 acids, and the end DRB1 0301-15-mers 9-mers position for each Each peptide is a portion of Each peptide is a peptide is the start SEQ ID NO: 9; each start portion of SEQ ID position plus eight I i eh NO: 11; each start position is specified, the lengthpsiio of peptide is 15 amino acids, the length of SVHTRPSQR 24 and the end position for each peptide is9 amino 19 peptide is the start position acids, a nd plus fourteen nte plus furteenposition for each iiiiiII~ilI~IIpeptide is the start Table XXI SEIWIHPQPQSQRRVT 18 position plus eight 109P1 v.5-A w 9- ers ]TMEIWIHPQPQSQRR 17 Each peptide is a SHPQPQSQRRVTFHLP 16 n HTRPSQRRV 10 portion of SEQ ID E IQ 10 aSVtHTRPSQ NO: 11; each start PSQRRVTFH position is specified, L D the length of Tblet oV ppeptide is 9 amino DRBI 0401-15- Table XXIII acids, and the end Each peptide is a portion of 109P1D4v.5 position for each SEQ ID NO: 9; each start A0201-9-mers peptide is the start position is specified, the position plus eight length of peptide is 15amino ________ acids, and the end position P_________P____R__F3 for each peptide is the start R position plus fourteen B PVSVHTRPS 10 WO 2004/098515 PCT/US2004/013568 224 Table XXVI Each peptide is a 109P1D4v.5-A26 portion of SEQ ID Table XXXII 9-mers NO: 11; each start 109P1D4v.5 Each peptide is a position is specified, B4402-9-mers prinof SEQ ID the length of Each peptide isa Oeach tion peptide is 9 amino portion o QD O eac trt acids, and the end NO: 11; each start position is specified, position for each position is specified the length of peptide is the start the length of peptide is 9 amino position plus eight peptide is 9 amino acids, and the end postion for achn position for each acids, and the end peptide is the start VHTRPSQRR 13 position for eah position plus eight RPSQRRVTF posion plus e ght HTRPSQRRV1 HRPSQRRV TRPSQRRVT RPSQRRVTF 15 1 ~~ SVHTRPSQRT [l F Table XXX Table XXVII 109P1D4v.5 Table XXXIII 109P1D4v.5 B2705-9-mers 109P1D4v.5 B0702-9-mers Each peptide is a B5101-9-mers Each peptide is a portion of SEQ ID Each peptide is a portion of SEQ ID NO: 11; each start portion of SEQ ID NO: 11; each start position is specified, NO: 11; each start position is specified, the length of position is specified, the length of peptide is 9 amino the length of peptide is 9 amino acids, and the end peptide is 9 amino acids, and the end position for each acids, and the end position for each peptide is the start position for each peptide is the start position plus eight. peptide is the start position plus eight peptide is eigt _________ ~RPSQRVT position plus eight RPSQRRRPSQRRVTF SRPSQRRVTF 22VHTRPSQRR RPSQRRVTF 13 HTRPSQRRV SVHTRPSQR 12 EHTRPSQRRV 11 T TRPSQRRVT 6TRPSQRRVT Table XXDill PSQRRVTFH 1091Dmv Table XXXIV B308-9-mers10PDv5A Each peptide is a Table XXXI 109PD4v.5 A portion of SEQ ID 109P1D4v.5 1O-mers NO: 11; each start B2709-9-mers Each peptide is a position is specified, Each peptide is a NO: o; eac st rt the length of portion of SEQ ID pO is ecifsed, peptide is 9 amino NO: 11; each start position is specified, acids, and the end position is specified, is lenof peptide position for each the length of is 10 amino acids, peptide is the start peptide is 9 amino and the end position position plus eight acids, and the end theory ar positive is position for each nine NRPSQRTF MI peptide is the start 7 SQR R=V position plus eight SVHTRPSQR 1HRPSQRRVT 2 SRPSQRRVTF 13 VVHTRESQR II Table XXIX RSRVF1 5 109PD4.5 TRPSQRRVT 11 B1510-9-mers TRPSQRRV 10 WO 2004/098515 PCT/US2004/013568 225 Table XX)V Each peptide is a 109PID4v.5 portion of SEQ ID Table XLII A0201-10-mers NO: 11; each start 109P1D4.5 Each peptide is a position is specified, B2705-1 0 portion of SEQ ID the length of peptde mers NO: 11; each start is 10 amino acids, iand the end position position for each peptide isNo Results the length of peptide Foeusta. isthe start position plus and the end position nn al LI for each peptide is Tabl XLIII~v. the start position plus f9 pvSV7=RPSQ [B27I091 0v. nine VHTRPSQRVmers fTJHTRPSQRRV 1 I HTRSQ FVT91 No Results f~ HRPSRRVT10 _______Found. SF PSQRRVTFHL Tid SSVHTRSQRRVSVHTRPSQR Tabblele PI 109P1 D4v.5-B4402 Table XXIX I 0-mers Tab9P1D9P1v.5. TabeXXVID v. Each peptide is a 109PI D4v.5 ac peptide0-mis portion of SEQ ID A0203-1 0- NO: 11; each start mers Mers portion of SEQ ID position is specified, NO: 11; each start the length of peptide No Results Lpsiio i secfid is 10 amino acids, foeahptdei an ch n psto h startpoionlu or na h p e t d is nin Table XXXVlI the s tai plu theendposition 1 09P1 D4v.5-A3 ine 10-mers jTRQRVF 1 Each peptide is a ~RSRVF 6 ~ SRVFL1 portion of SEQ ID [~ NO: ; each startP position is specifiedbl XL the length s peied, F on .if0a io cd ,frec peptide isSRR THL 1 is 10 amino acids, and the end position th start [si lus for each peptide is nine the start position plus nine t t] 1099P1Dv.55 Found. ISVHTRPSQRR 1 nr TleX V 145 jSPVSVHTRPSQ 1 uZ DB 11-5mr IITEach VT 13pid No Reut Eahpp12isaprino poto TRPSQVTFSQRRVTF NVSVHTRPSQR E SE ID N 11; each sa ~~~~~~position is specified, the-=PQRTTal L SjHTRPSQRRVT 11 abl id length of peptide 15 p iio tis Specfed ,i te r T X Iefor each peptides i s 0the start position plus marse FQPVSVHTRPSQSVTRSQR 2 1VSVHTRPSQRFound. F B0-10-r 13 ~~~Each peptide is a prino 11 SQ IDNO: 11; each start position is specified,th Tbe L length of peptideis1amn X cdand the end positions for I41 each peptide isthsar 109PI Dv.5-A2-1 0th e rstr position plus fute mnine VPVSVHTRPSHT HTRPSQRRVTRPQR I- WO 2004/098515 PCT/US2004/013568 226 Table XLVI-109P1 D4v.5 Table XXIII DRB1 0101-15-mers TableXLIX-109PID4v.5 109P1D4v.6 DRB1 0101-15-mers ,'emnlA2 Each peptide is a portion of L0 rera SEQ ID NO: 11; each start Each peptde isa portion of position is specified, the SEQ ID NO: 11; each start Each peptide is a length of peptide is 15 amino position is specified, the acids, and the end position for length of peptide is 15 amino NO: 13; each start each peptide is the start acids, and the end poition for position is position plus fourteen each peptide is the start specified, the position plus fourteen length of peptide is ____________________ amino acids, and [1I VTTFEVPVSVHTRPS| 16] the end position for RPSQRRVTFHLPEGS- 16 n3 TFEVPVSVHTRPSQR 2 6 each peptde is the n5I EVPVSVHTRPSQRRVI 115 start position plus P7 PVSVHTRPSQRRVTF 4 eight Thj VHTRPSQRRVTFHLP [|1 VTTFEVPVSVHTRPS 1 PI~1TRPSQRRVT HLE E4 WFEVPVSVHTRPSQRRH 113SVHTRPTDS 6F6 13 RPSQRRVTFHLPEGSRR Table XLVII-1 09P1 D4v.5 DRB1 0301-15-mers TbeXI 0P1Dv6TbeXI Each peptide is a portion of 'tria-l10PDv. SEQ ID NO: 11; each start 9C emnl position is specified, theIA23 length of peptide is 15 amino Ec etd sa9mr acids, and the end position for pro fSQI each peptide is the start N:1;ec tr position plus fourteen speifed 00 - -esT e Found.le XI 5 EVPVSVHTRPSQRRV 16 9aioais n 10 VHTRPSQRRVTFHLP 16thenpoionfrTbeX( YPVSVHTRPSQRRVTF 2 ec etd ste1914 STFEVPVSVHTRPSQRioegt9mr W VTTFEVPVSVHTRPS 9~IEc etd sa VSVHTRPSQRRVTFHHTPSRpotnofEQI LII LI ~~D NO3 ac tr i]SVHTRPSQRRVTFHL 8I ~ SHRT oiini 12TRPSQRRVTFHLPEG j seiedth 9 amnrcis n Table XLVIll-109P1D4v.5 9IDv6tendpsiofr DRB1 0401-1 5-mersC'tmna-20eahptieste Each peptide is a portion of 9-mers satpoionpu SEQ ID NO: 11; each startI position is specified, the prino E DL IIZI length of peptide is 15 amino acids, and the end position seiid h _______ for each peptide is the start l optdii nVH 1 position plus fourteen 9mo i a023 LIiiIIm~iiIi h n ito fo s TPQR lengVTTFEVPVSVHTRPS 22 Each peptide is t SEVPVSVHTRPSQRRV 20satpstoplsTbeXV ~FEVPVSVHTRPSQRR 18 ~TFEVPVSVHTRPSQR L4IL -Ctria (VSVHTRPSQRRVTFH I2] DRB 1101-5-mer Each peptde is a rino SEQ I NO:11; ach tart ~~~~~acids, and the end position forotnofSQI ~~~~~~each peptide is the start N:1;ec tr positon pus fu deposition s urteent [fljEVPV4 FEVPVio isVRSQRR VHTRPSQRRVTRPSRRVFHLEG 1thenpo i3infrTal|X 109 ppide sv.619PD~ LZJIPVSVHTRPSQRRVTF] ~ ~ C 12satpsto ls terminal-A E ETFE-VV9-mersr n1 IV TT FE VP V--V -T- P-] 9Each peptide is a: VSVHRPSRRVTHI q TTRP7TD:S portion of SEQ ID Ifl R::T 10NO: 13; each start n9 ~ ~ ~ ~ ~ ~ osto isHRSRRT I8poiini specified,, the TblX II length of peptide is ~9 amino acids, and Tabl XLVII-1 III DA5 19PIDv.6 the end position for DRBI040115-ers 'temina-AO each peptide is the Eachpepide s aporton f 9-ers start position plus SEQ D N: 11 eah sart achpeptde s eight 'a pTabeeaXport positipotio of SEQifed thD g 0 p pNO: 13; each start npositioniis specfied theh ~~~length of peptide is 1 mn 9s an cd, and acis, ndthe end positions for ~~ ~ ~ each peptide is the sati i 20 ~~start position plus TbeXV eight |0PD~. FEVPVSVTRPSQR 18 LPVSV~v. Table XXI] C'termina0 gFT-EVPVVHTRSQR A69-mers VSVTREachTF pepid 1sa0 WO 2004/098515 PCT/US2004/013568 227 Each peptide is a Table XXXI portion of SEQ ID Table XXIX 109P1D4v.6 NO: 13; each start 109P1D4v.6 CtermmalsB2709 position is C' terminal specified, the B1510-9-mers Each peptide is a length of peptide is Each peptide is a portion of SEQ ID 9 amino acids, and poin ofEQ ID NO: 13; each start the end position for ch st position is each peptide is the position is a specified, the start position plus specified, the length of peptide eight length of peptide is is 9 amino acids, 9 amino acids, and pasition for each SVHTRPTDS the end position for peptide is the start j PVSVHTRPTM 10ah pop isthest inl position plus eight SHTRPTDSRTM eight VSVHTRPTD VSVHTRPTD VHTRPTDSR 1 9HTRPTDSRT Table XXVII ] PVSVHTRPT 4 VHTRPTDSR 109P1D4v.6 HTPDR C' terminal-B0702HTP ST 9 - m e r s 1 0 9 P 1 DX v .6 Each peptide is a |Ta D 6'i 4 portion of SEQ ID 19P1 DI6 C' terminal-B259e specked, the Each peptide is a portion of SEQ ID length of peptide is portion of SEQ ID NO: 13; each start 9 amino acids, and NO: 13; each start position is the end position for position is secihfid pete each peptide is the specified, theleghopptd start position plus length of peptide is is 9 amino acids, eight 9 amino acids, and an th ed ____ _the end position for ption is tea reach peptide is the . PVSVHTRPT 1 start position plus position plus eight i HTRPTDSRT Q eight 1 1 4)IVHTRPTDSRI ~SVHTRPTDSI~ VHTRPTDSR PVSVHTRPT Table XXVIIIl[ HTRPTDSRT IE~HTRPTDSRT 109P1 D4v.6 fVSVHTRPTD ~ C' terminal-B08 Table XXXIVHRTS 919PD4v.6 Each peptide is a C' terminal-B2709 portion of SEQ ID 9-mars Table XXXIll N:13; each start 109P1 D4v.6 position is Each peptide is a specified, the prinoSEID9-mers length of peptide is NO: 13; each start 9 amino acids, and position is the end position for specified, the each peptide is the length of peptide start position plus is 9 amino acids, speightand the end the eighpositonfo position for each peptide is the start 1 SVHTRPTDS -position plus eight

IHTRPTDSRT

WO 2004/098515 PCT/US2004/013568 228 Each peptide is a Table Each peptide is a portion of SEQ ID XXXVI portion of SEQ ID NO: 13; each start 109P1D4v.6 NO: 13; each start position is C' terminal- position is specified, specified, the A0203 the length of peptide length of peptide 10-mers and1them dn o n is 9 amino acids, ______and the end position ad 9 ainid, for each peptide is pos to n for each NoIReults the start position plus peptide is the start Found. nine position plus eight ETable XXXVII VPVSVHTRPT VSVHTRPTD 109PID4v,6______ VSVHTRPTD C terminal-A3 VHTRPTDSRT SSVHTRPTDS 1O-mers HTRPTDSRT Each peptide is a Table ti D

XL

portion of SEQ ID109P1D4 Table XXXIV NO: 13; each start v.6-C 109P1D4v.6 position is specified, terminal C terminal-Al the length of peptide B08 I 0-mars is 10 amino acids, and the end position Each peptide is a for each peptide is portion of SEQ ID the start position plus No NO: 13; each start nine Results position is specified, Found. the length of peptide is 10 amino SVHTRPTDSR acids, and the end PVSVHTRPTD Table position for each

XLI

peptide is the start 109P1D4 position plus nine Table XXXVIII v.6-C' I _ _ 109P1 D4v.6 terminal C' terminal-A26 B1510 VSVHTRPTDS 10-mers 10-mers SSVHTRPIDSR Each peptide is a portion of SEQ ID Table XXXV NO: 13; each start Results 109P1D4v.6 position is specified, Found. C' terminal-A0201 the length of peptide 1 0-mars is 10 amino acids, and the end position Table Each peptide is a for each peptide is XLl portion of SEQ ID the start position plus 109P1 D4 NO: 13; each start nine v.6-C' position is specified, terminal the length of B2705 peptide is 10 amino EISVHTRPTDSR 12 acids, and the end PVSVHTRPTD11 position for each peptide is the start i position plus nine Table XXXIX Resuts 109P1D4v.6 Found. C' terminal-B0702 H SVHTRPTDSR 8 10-mers Table XLIII i VPVSVHTRPT I 5 109P1D4v.6 SPVSVHIRPTD I1 C' terminal 4 6R2709 10-mers

[_IZII

WO 2004/098515 PCT/US2004/013568 229 No Results Each peptide is a portion of Each peptide is a Found SEQ ID NO: 13; each start portion of SEQ ID position is specified, the NO: 13; each start length of peptide is 15 amino position is specified, Table XLIV acids, and the end position the length of peptide 109P1D4v.6 for each peptide is the start is9 amino acids, C' terminal-B4402 position plus fourteen and the end position 10-mers for each peptide is Each peptide is a the start position portion of SEQ ID EVPVSVHTRPTDSRT 16 plus eight NO: 13; each start TFEVPVSVHTRPTDS position is specified, VTTFEVPVSVHTRPT NTDS9VR the length of ___2__________ peptide is 10 amino 21HKCLLSGTY 15 acids, and the end Table XLVIII-109P1D4v.6 M8VGFNSDI position for each C' terminal-DRB1 0401 T TNCHKCLL peptide is the start 15-mers position plus nine Each peptide is a portion of TNCHKCLLS SEQ ID NO: 13; each start j PVSVHTRPTD position is specified, the Table XXI length of peptide is 15 amino 10P 1D4v.6 SVHTRPTDSR acids, and the end position N' terminal-A0201 VPVSVHTRPT for each peptide is the start 9-mers position plus fourteen h Each peptide is a Table XLV portion of SEQ ID 109PID4v.6 VTTFEVPVSVHTRPT 22 NO: 13; each start C'terminal- -positionisspecified, C' HIFEVPVSVHTRPTDSR henn is spfie B5101the length of peptide 10-mers ITFEVPVSVHTRPTDS 4 is 9 amino acids, 5 EVPVSVHTRPTDSRT 1 and the end position for each peptide is No Results the start position Foun.J Table XLIX-1 09P1 D4v.6 plus eight C' terminal-DRBI 1101 Table XLVI-1 09P1 D4v.6 15-mers E SDS VRV20 C' terminal-DRB1 0101i Each peptide is a portion of 15-mers SEQ ID NO: 13; each start F GFNSDISSV 18 Each peptide is a portion of position is specified, the ___CLLSGIF17 Ech ptidN e s tartio of length of peptide is 15 amino SEQ iD N 13 each start acids, and the end position MTVGF.SDI 1 position is:specified, the for each peptide is the start TTNCHKCLL 15 length peptIde is 15 amino position plus fourteen acids, and the end position SSVRVNTT for each peptide is the start El FNSDSSVV 12 position plus fourteen n3 TFEVPVSVHTRPTDS 25 _________________~ ___ _____jINTTNCHKCL 12 {EVPVSVHTRPTDSRT 1ElDISSVVRVN 1 3 TFEVPVSVHTRPTDS 1 VTTFEVPVSVHTRPT 13 KCLLSGTYI 11 DlVTTFEVPVSVHTRPT 16 H]FEVPVSVHTRPTDSR 14 Table XXII 109P1D4v.6 Table XXIV El N' terminal-Al 109P1 D4v.6 9-mrs N' terminal TableXLVIl-109P1D4v.6 A0203 C' terminal-DRB1 0301 9-mers 15-mers No Results Found.

WO 2004/098515 PCT/US2004/013568 230 Table XXV Table XXVII 109P1D4v.6 109PID4v.6 Table XXIX N' terminal N' terminal-B0702 109P1D4v.6 A3-9-mers 9-mers N' terminal-B1510 Each peptide is a Each peptide is a 9-mers portion of SEQ ID portion of SEQ ID Each peptide is a NO: 13; each start NO: 13; each start portion of SEQ ID position is specified, position is specified, NO: 13; each start the length of peptide the length of peptide position is specified, is 9 amino acids, and is 9 amino acids, the length of peptide the end position for and the end position is 9 amino acids, each peptide is the for each peptide is and the end position start position plus the start position for each peptide is eight plus eight the start position E I I plus eight 14RVNTTNCHK ISSVRVNT 12 SVVRVTN NTTNCHKCL 1 TTNCHKCLL 12 CLLSGTYF 8 TTNCHKCLL NTTNCHKCL 10 VRVNTTNC 14 FNSDISSW 920 CHKCLLSGT 10 ~jNSDISSVVR 3 SDISSVVRV ElISSVVRVNT E DISVVRVN 3 KCLLSGTYI 2 CLLSGTYIF 7 HKLLSGTY MTVGFNSDI DISSVVRVN 10 SSVRVNTT El Table XXVI CLLSGTYIF Table DO6 109P1D4v.6 GFNSDISSV N t-9PID4.6 N' trminl-A2 N'terminal-B2705 'temina A26 CHKCLLSGT 9-mers Each peptide is a Each peptide is a portion of SEQ ID portion of SEQ ID Table XXVIII NO: 13; each start NO: 13; each start 109PID4v.6 position is specified, position is specified, N' terminal-B08 the length of peptide the length of peptide 9-mers is 9 amino acids, and is 9 amino acids, and Each peptide is a the end position for the end position for portion of SEQ ID each peptide is the each peptide is the NO: 13; each start start position plus start position plus position is specified, eight eight the length of peptide is 9 amino acids, and DISSVVRVN the end position for VRVNTTNCH 6 Each peptide is the RVNTTNCHK NTTNCHKCL start position plus CLLSGTYIF 5 17 TTNCHKCLL 17 eight EL NSDISSVVR 14 SVVRVNTTN KCLLSGTYl 1 ElMTVGFNSDI 1 1 SSRVNTT 2 21 HKCLLSGTY 13 23 CLLSGTYIF HKCLLSGTY 2 21]TVGFNSDIS NTTNCHKCL MTVGFNSDI VVRVNTTNC TTNCHKCLL TTNCHKCLL 11 F2SDISSVVRV 18TNCHKCLLS NTTNCHKCL 10 SSVVRVNTT 2 CHKCLLSGT 0 4 RVNTTNHK RVNTTNC Table XXXI 14L0 1 1O9P1D4v.6 CLLSGT_ F E MTVGFNSDI , N' terminal-B2709 SKCLLSGTYI 9-mers WO 2004/098515 PCT/US2004/013568 231 Each peptide is a Each peptide is a portion of SEQ ID portion of SEQ ID j VGFNSDISSV 18 NO: 13; each start NO: 13; each start S~ N ISWV 1 position is specified, position is specified, L I the length of peptide the length of peptide 23CLLSGTYIFA 16 is 9 amino acids, and is 9 amino acids, EDISSVVRVNT the end position for and the end position each peptide is the for each peptide is S start position plus the start position NTTNCKCLL3 eight plus eight GFNSD!SSVV [ GF I 13 s 152VNTTNCHKCL SGFNSD ISSV KCLLSGTYI 1 NCHKCLLSGT SDISSVVRV 1MTVGFNSDI 22KCLLSGTYl FNSDSSW - Table XXXVI 23 CLLSGTYiF 712 SDISSVVRV 1 109PID4v.6 13VRVNTTNCH 11 DISSVVRVN N' termina -A0203 I 0-mers 16NTTNCHKCL 11 VGFNSDISS Each peptide is a 17TTNCHKCLL 1GFNSDISSV portion of SEQ ID lMTVGFNSDI NTTNCHKCL NO: 13; each start FNSDISSVV TTNHKLL position is specified, L~~I the length of peptide is 10 amino acids, Table XXXiI Table XXXIV and the end position 109P1D4v.6 109PID4v.6 for each peptide is N' terminal N' terminal-Al the start position B4402-9-mers 10-mers plus nine Each peptide is a Each peptide is a portion of SEQ ID portion of SEQ ID NO: CLLSGTYIFA 10 NO: 13; each start 13; each start position position is specified, is specified, the length the length of peptide of peptide is 10 amino Table XXXVII is 9 amino acids, acids, and the end 109P1D4v.6 and the end position position for each N' terminal-A3 for each peptide is peptide is the start 10-mers the start position position plus nine Each peptide is a plus eight portion of SEQ ID NO: E] NSDISSVVRV 15 13; each start position - H is specified, the length 6NTTNCHKCL 1CKCLLSGTY of peptide is 10 amino 21 HKCLLSGTY 12 TNCHKLLS acids, and the end SCLLSGTYF NTNCHKCLL position for each 173 TTCHC 11 T C K L peptide is the start FIT-TN CH KC LL position plus nine 2 KCLLSGTYI 1 Table XXXV ]MTVGFNSDI [' tr9P D4v.6 VVRVNTTNCH 17 N' terminal-A0201 10-mers SVRVNTTNC15 Table XXXIv Each peptide is a RVNTTNHKC14 109P1D4v.6 portion of SEQ ID NO: Ej FNSDISSVVR 1 N'terminal-s5101 13; each start position 9-mers is specified, the length lISSVVRVNT of peptide is 10 amino TVGFNSDISS 1 acids, and the end CHKCLLSGTY 1 position for each ~ peptide is the start g CLLSGTYlFA 12 position plus nine VRNTNCHK 11] WO 2004/098515 PCT/US2004/013568 232 Table XXXVII Each peptide is a 109P1D4v.6 portion of SEQ ID NO: N' terminal-A3 13; each start position Results 10-mers is specified, the length Found. of peptide is 10 amino Each peptide is a acids, and the end portion of SEQ ID NO: position for each Table 13; each start position peptide is the start XLIll is specified, the length position plus nine 109P1D4 of peptide is 10 amino v.6 N' acids, and the end terminal position for each DISSVVRVNT B2709 peptide is the start NDSVR position plus nine i 0~ers 22KCLLSGTYlF 1VNTTNCHKCL Results [ANTTNCHKCLL 10Found. Table XXXVIII 22 KCLLSGTYIF 109P1D4v.6 GFNSDISSVV F -Table XLIV-109P1D4 N' tern 1 NCHKCLLSGT v.6 N' terminal . t0-mers HKCLLSGYB4402-10-mers Each peptide is a Each peptide is a portion of SEQ ID NO: CLLSGTYlFA portion of SEQ ID NO: 13; each start position VGFNSDISSV 13; each start position is seciied th legthLIIL~J13; each str posiion is specified , the length is specified, the length lis specified, the length of peptide is 10 amino of peptide is 10 amino acids, and the end Table acids, and the end position for each XL- position for each peptide is the start 109P1D4 peptide is the start position plus nine v.6 N' position plus nine terminal B08 NTTNCHKCLL 7 10-mers KCLLSGTYIF VVR VNTTNC_ 15VNTTNCHKCL 13 F TVGFNSDISS No NTTNCHKCLL 13 DISSVVRVNT g Results 20 CHKCLLSGTY 11 n1 FM-T - ~~Found.F2]HCLG l 9 MTVGFNSDIS 12 HKCLLSGTY 20 CHKCLLSGTY 12Table SRVNTTNCHKC11

XLI

[M VGFNSDISSV g 109P1D4 Table SDISSVVRVN 0 v.6 N'

XLV

10 L terminal 109P1 D4 1 WRVNTTNCH C B1510- v.6 N' 17 TTNCHKCLLS 10-mers terminal VNTTNCHKCLB5101 HEMNo IlO-mers Table XXXIX Found. 109P1D4v.6 -- n N' terminal-B0702 10-mers Table Found.

XLII

109P1 D4 Table XLVI-1 09P1 D4v.6 v.6 N' N' terminal-DRBI 0101 terminal 15-mers B2705 10-mers WO 2004/098515 PCT/US2004/013568 233 Each peptide is a portion of Table XLVIII-109PID4v.6 Table XXII SEQ ID NO: 13; each start N'terminal-DRBI 0401 109PID4v.7 position is specified, the 15-mers N'terminal-Al length of peptide is 15 amino Each peptide is a portion of 9-mers acids, and the end position for SEQ ID NO: 13; each start Each peptide is a each peptide is the start position is specified, the portion of SEQ ID position plus fourteen length of peptide isi1 amino NO: 15; each start _________77____ acids, and the end position for position is specified, FIi NCHKCLLSGTYFAV 26 each peptide is the start the length of 1191 position plus fourteen peptide is 9 amino j2] TVGFNSDISSVVRVN 2 acids, and the end [ ~ ~-1 F5]1TTCK 2 ________ position for each F91ISSVVRVNTTNCHKC] 22 ______________ ~ JTVGFNSDISSVVRVNI 28 peptide is the start F0SSVVRVNTTNCHKC [iIISSWVNTTCHKL 11 ~NSDSSV rVNTNC [6 position plus eight SCHKCLLSGTYFAVLISSRVNTTNCHKC HKCLLSGTYFAVLL 1iSSRVNTTNCHKCL 22 KCLLSGTYIFAVLLV 116 F1]1 TNCHKCLLSGTYIFA 15H E K IVLL 6l NSDISSVVRVNTTNC Li L1 SssSLSP Table XLIX-1 09P1 D4v6 Table XLVII-11 09P1 D4v.6 N' terminal-DRIB1 1101 Table XXIII N' terminal-DRB1 0301 E 5-mers 109P1D4v.7 peptide Each peptide is N'terminal-A0201 Each peptide is a portion of SEQ ID NO: 13; each start 9-mers SEQ ID NO: 13; each start position is specified, the Each peptde is a position is specified, the length of peptide is 15 amino portion of SEQ ID length of peptide is 15 amino acids, and the end position for NO: 15; each start acids, and the end position for each peptide is the start position is specified, each peptide is the start position plus fourteen the length of peptide position plus fourteen j is 9 amino acids, F-12 and the end position F2 VFNDSVRV 19 NSDISSVVRVN=TTNC L1for each peptide is LiTVGFNSDISSVVRVN W|192 SSVVRVNTTNCHKC the start position NSDISSVVRVNTTNC 16]_1____________12 plus eight I] HKCLLSGTYIFAVLL H1 WI HKCLLGTYIFAVL L~l 14RVNTTNCHKCLLSGT [LI I LVMVV 3 Ej ISSVVRVNTTNCHKC| 12 Li LISSSSSL 10SSVVRVNTTNCHKCL Table ))Il- LSPL L LVS 2 CHKCLLSGTYIFAVL I09P1D4v.72 I VVRVNTTNCHKCLLS F N'terminal-Al giKCLLSGTYlFAVLLV 119mr 12]] KCLLSGYIFAVLLV LIEach peptide is a SPLSW 1 M1 TNCHKCLLSGTYIFA ipportion of SEQ ID FSSSSS=SPL 1 NO: 15; each start jE LLSVRV 1 Table XLVI1-109P1D4v.6 position is specified, jr FLlssss 5 N' terminal-DRBI 0401 the length of 15-mers peptide is 9 amino ___________________acids, and the end Table XXIV Each peptide is a portion of position for each 109P1D4v.7 SEQ ID NO: 13; each start peptide is the start N'terminal position is specified, the position plus eight A0203 length of peptide is 15 amino __ 9-mers acids, and the end position for each peptide is the start position plus fourteenE 12 aS n o S _D N F ound WO 2004/098515 PCT/US2004/013568 234 Table XXVII Table XXVIII Table XXV 109P1D4v.7 109P1D4v.7 109PID4v.7 N' terminal-B0702 N' terminal-B08 N' terminal-A3 9-mers 9-mers 9-mers Each peptide is a Each peptide is a Each peptide is a portion of SEQ ID portion of SEQ ID portion of SEQ ID NO: 15; each start NO: 15; each start NO: 15; each start position is specified, position is specified, position is specified, the length of peptide the length of peptide the length of peptide is 9 amino acids, is 9 amino acids, is 9 amino acids, and the end position and the end position and the end position for each peptide is for each peptide is for each peptide is the start position the start position the start position plus eight plus eight plus eight 1 SPLLLVSW 1 LLVSVVRVN 7PLLLVSVVR 26SSSLSPLLL 1 14 SLSPLLLVS 2 10 SSSSSLSPL 1 Table XXIX SFLlISSSSS 11SSSSLSPLL N13 t9PID4v.7 _ -1 f~-s7sP:L N' terminal-Bi16lO j RVGFLSS 1 MFRVGFL 1 9-mers F7 LIISSSSSL 1SSLSPLLLV Each peptide is a 18LLLVSVVRV LVSVVRVNTH portion of SEQ ID 20LSVRN 16 7] ISSSL 1 NO: 15; each start LSVV LlSSSSSL |position is specified, 1LLVSVVRVN LLLVSVVRV the length of peptide F ISSSSSLS is 9 amino acids, and the end position Table XXVIII for each peptide is Table XXVI 109P1 D4v.7 the start position 109P1D4v.7 N' terminal-B08 plus eight N' terminal-A26 9-mers _ 9-mers Each peptide is a SSSSLSPL L 12 Each peptide is a portion of SEQ ID portion of SEQ ID NO: 15; each start SSSLSPLLL| NO: 15; each start position is specified, 10SSSSSLSPL 11 position is specified, the length of peptide L_ lSSSSSL_| the length of peptide is 9 amino acids, is 9 amino acids, and the end position LLLVSVVRV and the end position for each peptide is for each peptide is the start position the start position plus eight Table XXX L plus eight F ]0 9PID4v.7 pu e N' terminal-B2705 IIzIz1I ELLIISSSSSL 19-mers E LLIISSSSSL MFRVGFL 13 Each peptide is a RVGFLIISS 11 SSSLSPLLL 13 portion of SEQ ID 0s SSSLSPL 15 SSSSLSPL 12 NO: 15; each start 1-01 9F1 position is specified, [4J VGFLlISSS SSSSLSPLL 12 the length of peptide SSSSLSPLL VSVVRVNTT 11 is 9 amino acids, R and the end position 1 SSSLSPLLL 1 16 SPLLLVSW 10 for each peptide is 20 LVSVVRVNT 1 18 LLLVSVVRV I EI]the start position 1 SLSPLLLVS F plus eight PLLLVSVVR ff FLISSSSS E1 LSS 17 WO 2004/098515 PCT/US2004/013568 235 Table XXX Table XXXII Each peptide is a 109P1D4v.7 109P1D4v.7 portion of SEQ ID N' terminal-B2705 N' terminal-B4402 NO: 15; each start 9-mers 9-mers position is specified, Each peptide is a Each peptide is a th leno pide portion of SEQ ID portion of SEQ ID an o cids, NO: 15; each start NO: 15; each start a h eption position is specified, position is specified, for each petide is the length of peptide the length of peptide nine is 9 amino acids, is 9 amino acids, and the end position and the end position for each peptide is for each peptide is HiSSSSLSPLLL1 the start position the start position 1 plus eight . plus eight _ FRVGFLllS 15 1SSSLSPLLL 10 SSSSSLSPLL E SSSSSLSPL 3 LIISSSSSL 1 SLSPLLLV M 11 SSSSLSPLL 13 1 SSSSSLSPL Table XXXV SSSLSPLLL 3 SSSSLSPLL 3 IPD4.7 E[RVGFLlSS 0 MFRVGFLII 0N'terminal VGFLllSSS SLSPLLLVSA0201-10-mrs MFRVGFLEach peptide is a GFLISSSS Table XXXIIportion of SEQ ID XXX- NO: 15; each start 109PID4v.7 position is specified, N' terminal-B5101 the length of peptde Table XXXI 9-mers is 10 amino acids, 109PID4v.7 Each peptide is a and the end position N' terminal-B2709 portion of SEQ ID for each peptide is the 9-mers NO: 15; each start start position plus Each peptide is a position is specified, nine portion of SEQ ID the length of NO: 15; each start peptide is 9 amino ________________32 position is specified, acids, and the end 1 V the length of peptide position for each FLIISSSSSL 25 is 9 amino acids, peptide is the start and the end position position plus eight L for each peptide is _ _ _ the start position plus eight 16 SPLLVSVV | LLvSVRVNT H 18]LLLVSVVRV|17 SSSLSPLLLV 17 18 LLLVSRV MFRVGFL 13 LVS VNTT 17 LSSSSSL LSPLLLVSV ISSSSLSPL 11 SSSSLSPLL 12 16 SSLSPLLLV Table XXXIV 109P1D4v.7 Table SFRVGFLIS N' terminal-Al xxxvi 10SSSSSLSPL 1 10-mars 109P1D4v.7 9 - - FillN' terminal 1 SSSLSPLLL A0203-1 0 1SPLLLVSW 11 W MFRVGFLII__l__ 1N 15; eh estts a Found.

WO 2004/098515 PCT/US2004/013568 236 Table XXXVii Table XXXIX No Results 109P1D4v.7 109P1D4v.7 Found. N' terminal-A3 N' terminal-B0702 10-mers 10-mers Table XLI Each peptide is a Each peptide is a 109PD4v.7 portion of SEQ ID portion of SEQ ID N'terminal NO: 15; each start NO: 15; each start B2709 position is specified, position is specified, 10-mers the length of peptide the length of peptide is 10 amino acids, is 10 amino acids, and the end position and the end position for each peptide is the for each peptide is the start position plus start position plus nine nmne ninenineTable XLIV SLSPLLLVSV ISSSSSLSPL 1N' trminal-B4402 RVFLSSS SSSSLSPLLL0-mrs FLSSSSSL Each peptide is a EIFFIISSSSS 19Fs s-s-s-Ls-P::L1E13portion of SEQ ID 1 PLLLVSVVRV 17 16 SPLLLVSWR 1 NO: 15; each start SPLLLVSWR SLSPLLLVSVposition is specified, 8 LLLL the length of pptide 16 E]1101ssss-]i is 10 amino acids, 8 IISSSSLSP 1 12 SSSLSPLLLV 10 and the end position ___________ for each peptide is 1LLVSVVRVNT 117PLLLVSVVRV F1 9 15EFEL-vsWR-- 9the start position plus L LSSSSSLS 14 19LLVSVVRVNT nine LVSRVNTT 1LVSVVRVNTT SSLSPLLLVS 10 9 LSPLLLVSVV E FL FSSS 13 Table XXXVIII Table XL SSSSSLSPLL 13 109P1D4v.7 109PID4v.7 N' terminal N' terminal A26-10-mers B08 10-mars Table XLV Each peptide is a 10-mers portion of SEQ ID N'terminal NO: 15; each start No ResutsB5101 position is specified, . 0-mars the length of peptide is 10 amino acids, and the end position Table XLI No Results for each peptide is the 109P1D4v.7 Found start position plus N' terminal nine B1510 10-mers TableXLVI-109P1D4v.7 [ RVGFLlSSS 16 N'terminal-DRBI 0101 20 LVSVVRVNTT No Results 15-mars R i l Each peptide is a portion of EIF-LI=ISSSS 14SEQ ID NO: 15; each start FLIISSSSSL ISSSSSSLSPL position is specified, the Table XLII length of peptide is 15 amino SSSSLSPLLL 11109P1D4v.7 acids, and the end position for FRVGFLIISS 10 N' terminal- each peptide is the start B27 05 F~i LIISSSLS i~ 2705 position plus fourteen LilSSSSSILS 010-mers IN em 10-mars No RVGFLSSSSSLSP WO 2004/098515 PCT/US2004/013568 237 Table XLVI-I09PD4V.7 XLVIII-109PD4v.7 Table XXII N' terminal-DRBI 0101 N'terminal-DRB1 0401 109P1D4v.8-AI 15-merss 1 5-mers 1 5-mers 9-mar Each peptide is a portion of Each peptide is a portion of Each peptide is a SEQ ID NO: 15; each start SEQ ID NO: 15; each start portion of SEQ ID position is specified, the Position is specified, the NO: 17; each start length of peptide is 15 amino length of peptide is15 amino position is acids, and the end position for acids, and the end position for specified, the each peptide is the start each peptide is the start length of peptide position plus fourteen_ position plus fourteen is 9 amino acids, position for each [~jMFVGFIISSSL 5 ~ ]RVGFLIISSSSSLSP 28peptide is the start MFRVGFLSSSSSL 25 RVNTTNC position plus eight MIVGFLIlS-SSSSLSPL 5 SSSLSPLLLVSVRV 24 MFRVGFLIISSSSSL 20 15 VGFLIISSSSSLSPL 20 9 ISSSSSLSPLLLVSV m21 2LVSVVRVNTTNCHKC [2 1RN 20 EM88 SFRVGFLSSSSSLSLS 13 SSLSPLLLVSVVRVN 7L 1po E ID Table XLV-109P1D4v.714 N' terminal-DRB1 0301 VS RVNT L 1leghoppte s 15-mers219aioaisan the P e d v po ito Each peptide is a portion of SEQ ID NO: 15; each start position is specified, theNs length of peptide isi1 amino acids, and the end position for , each peptide is the start Se I NO: 1 c rG E position is specified, thefourteen _____________length of peptide is 15 amino 15-r EVplu 16gh VGFLISSSSSLSPL 20acids, and the end position for Ec peptiTe 14 Leach peptide is the start NO15eahsrtH FPGLKKIV 1 position plus fourteen 1tLSPLLLVSVVRVNTT 15 peptdI_ s1amio1 VGLISSSS 20SSSS each Tabled istXIVat GFLIISSSSSLSPLL L4 I L9PID4v.8 6 FLIISSSSSLSPLLL 131 PLLLVSVVRVNT 22 A0203-9 SSSLSPLLLVSWRV| I MFRVGFLIISSSSSL 18 ISSSSSLSPLLLVSV 12 1LSpLLLVSVVRVNTT 14 SPLLLVSVRVNTTN 12 FRVGF S 13 Results 20LVSVVRVNTTNCHKC 12 GFLIISSSSSLSPLL 13d 21 VSVVRVNTTNCHKCL 1 LLLVSVRVNTTNCH 1 Table XXV RVGFLlSSSSSLSP 1 FLIISSSSLSPLLL 1 109PD4v.8 IISSSSSLSPLLLVS 11 SSSLSPLLLVS A3-9-mers LLLVSVVRVNTTNCH 11 20 LVSVVRVNTTNCHKC MFRVGFLISSSSSL 10C PLLLVSWRVNTTN X 9LIISSSSSLSPLLLV 10 WO 2004/098515 PCT/US2004/013568 238 Each peptide is a Table XXVII Table XXIX portion of SEQ ID 109P1D4v.8 109P1D4v.8 NO: 17; each start B0702-9-mers B1510-9-mers position is Each peptide is a Each peptide is a specified, the portion of SEQ ID portion of SEQ ID length of peptide is NO: 17; each start 'NO: 17; each 9 amino acids, and position is start position is the end position specified, the specified, the for each peptide is length of peptide length of peptide the start position is 9 amino acids, is 9 amino acids, plus eight and the end and the end LIZIIIZIposition for each position for each peptide is the start peptide is the LKi TVQposition plus eight start position plus K~IE!TVQPTV 11~1eight jIFIPGLKKEIl1 KKETVQPT _ ___ ~LKK EITVQP ~ ~TFIPGLKKE 2 [TFIPGL~KKE Il Table XXVIll | FIPGLKKEI l 109P1D4v.8 IPGLKKEIT |$ Table XXVI B08-9-mers LKKEITVQPl 109P1D4v.8 Each peptide is a A26-9-mers portion of SEQ IDTalXX Each peptide is a iNO: 17; each start 09P1D v.8 portion of SEQ ID position isB NO: 17; each start specified, the B759mr position is length of peptide is Each peptide is a specified, the 9 amino acids, and portion of SEQ ID length of peptide the end position NO: 17; each start is 9 amino acids, for each peptide is position is and the end the start position specified, the position for each plus eight length of peptide is peptide is the start _________9 amino acids, and position plus eight IPGLKKEIT 8tfe ech postioeni _________ ~GLKKEITVQ 8 the start position, TFIPLKKEFIPGKK_ plus eight SFIPGLKKEl ~J FLKKEIQ ~LKKEITVQP PLKKEITV GLKKEITVQ|1 [KEITVQPTV GL ETVFIPGLKKEI l1 Table XXIX KEITVQPTV|[~ Table XXViI 109P1D4v.8 []TFIPGLKKE|[~ 109P1D4v.8 B1510-9-mers PGLKKEITV|W B0702-9-mers Each peptide is a Each peptide is a portion of SEQ ID TbeXX portion of SEQ ID NO: 17; each TbeX~ NO: 17; each start start position is B279-9-me 8 position is specified, the B799mr specified, the length of peptide length of peptide is 9 amino acids, is 9 amino acids, and the end and the end position for each position for each peptide is the peptide is the start start position plus position plus eight eight j2|PGLKKElT 18GLKKEITVQ| WO 2004/098515 PCT/US2004/013568 239 Each peptide is a Table XXXIV Each peptide is a portion of SEQ ID 109P1D4v.8 portion of SEQ ID NO: 17; each start A1-10-mers NO: 17; each start position is Each peptide is a position is specified, specified, the portion of SEQ ID the length of peptide length of peptide NO: 17; each start is 10 amino acids, is 9 amino acids, poiini pcfeand the end position and th emncd, position is specified, for each peptide is and the end the length of the start poition position for each peptide is 10 amino psin peptide is the start acids, and the end plus nine position plus eight position for each 1 l l 1lpeptide is the start GLKKEITVQP RKEITVQPTV| 1 position plus nine KEITVQPTVE 1 P PGLKKEITV FE 1 FIPGLKKEIT NJ FIPGLKKEI l S P SKKEITVQPTV ~Table XXXVIII Table XXXII 109P1 D4v.8 109P1D4v.8 Table XXXV A26-10-mers B4402-9-mers 109P1 D4v.8 Each peptide is a Each peptide is a A0201-10-mers portion of SEQ ID portion f SEQ D Each peptide is a NO: 17; each start NO: 17; each start portion of SEQ ID position is position is NO: 17; each start specified, the length specified, the position is specified, of peptide is 10 length of peptide the length of peptide amino acids, and is 9 amino acids, is 10 amino acids, the end position for and the end and the end position each peptide is the position for each for each peptide is start position plus peptide is the start the start position nine position plus eight, plus nine _ FGSTFIPGLKKE 18 SKEITVQPTVg 16[2 FIPGLKKEIT 5 FPGLKKEl 124 IPGLKKEITV 4 Table XXXIX TFIPGLKKE 10 TFIPGLKKEl 1 B0702-10ers M|KKEITVQPTV 13 Each peptide is a Table XXXIII |STFIP.GLKKE 1 portion of SEQ ID 109P1 D4v.8 GLKKE!TVQP 2 NO: 17; each start B50--mr LKKEITVQPT 1psti on is specified, Each peptide is portion of SEQ ID peptide is 10 amino NO: 17; each start Table acids, and the end position is XXXVi position for each specified, the 109P1D4v.8 peptide is the start length of peptide A0203-10. position plus nine is 9 amino acids, mers _________ and the end F 1 _PGLKKEITV_ position for each I peptide is the start No Results l FIPGLKKEIT position plus eight FonddLKKEITVQPT _________ Tble XXVI [~KKEiTVQPTV ~] PGLKEITV 2110 P1D v8 :FIPGLKE 1 A3-10-mers Table XL spPGLKKEIT 1 109P1 D4v.8 KetVQP 1 mpie3e Tabl KEITQPT 13IVQ mers WO 2004/098515 PCT/US2004/013568 240 Table XLVIII-109P1D4v.8 No Results Table XLV DRB1 0401-15-mers 109P1D4v.8 Each peptide is a portion of B5101-10- SEQ ID NO: 17; each start mers position is specified, the Table XLI length of peptide is 15 amino 1 09P1 D4v.8 acids, and the end position B1510-10- No Results for each peptide is the start mers Found. position plus fourteen Table XLVI-1O9PID4v.8 F Results Tab 0101-15-mrs .8] STFIPGLKKEITVQP l20 Each peptide is a portion of F1IPGLKKEITVQPTVE 1 Table XLI I SEQ ID NO: 17; each start 5]j ESTFIPGLKKEITVQ 16 109PID4v.8 position is specified, the ________________] length of pptid is 15 amino 13KKEITVQPTVEEASD1 B2705-10- acids, and the end position 2 ISDPESTFIPGLKKE [12J mers for each peptide is the start 1DPESTFIPGLKKEIT |12 position plus fourteen PGL KKETVQPTVEI ound.ults IPGLKKEITVQPTVE F GLKKEITVQPTVEEA|121 Tabl e XLII [11 MKKEITVQPTVEEASD 2 Table XLIX-1 PI D4v.8 09 D8 [ ESTFIPGLKKEITVQ 19 DRB11101-15-mers B2709-10- DPESTFIPGLKKEIT I 7 Each peptide is a portion mers STFIPGLKKEITVQP 6 of SEQ ID NO: 17; each LE 13start position is specified, LKKE1TVQPTVEEAS 3 the length of peptide is 15 No Results amino acids, and the end FnTable XLVII-109P1D4v.8 position for each peptide is DRB1 0301-15-mers the start position plus Tal 09PLDv8 Each peptide is a portion of fute 109 D48 SEQ ID NO: 17; each start JSTFIPLKETVQP B4402-10-mers position is specified, the ESTFIPGLKKETVQ 8 Each peptide is a length of peptide is 15 amino GLKKEITVQPTVE 2 portion of SEQ ID acids, and the end position R 1 lP NO: 17; each start for each peptide is the start position is specified, position plus fourteen the length of peptide is 10 amino acids, and the and ESTFIPGLKKEITVQ r7] position for each STFPGLKKEITVQP 17 peptide is the start 3lKET PVEADI1 position plus nine KKElTVQPTVEEASD[3 IPGLKKEITVQPTVE 12 RIKEITVQPTVE 17I NSDPESTFIPGLKKE E] I TFIPGLKKEl 6 WO 2004/098515 PCT/US2004/013568 241 Table L: Protein Characteristics of 109P1D4 109P1D4 var.1 Bioinformatic URL on World Wide Web Outcome Program R846-3911 bp (includes stop codon) Protein length 1021aa Transmembrane TM Pred .ch.embnet.org/ 3 TM helices (aa3-aa23, aa756 region aa776, aa8 I 6-aa834), N terminus intracellular HMMTop .enzim.hu/hmmtop/ no TM, N terminus extracellular Sosui .genome.ad.jp/SOSui/ 3 TM helices (2-24aa, 756-778aa, 810-832aa), N terminus extra cellular TMHlMM .cbs.dtu.dk/services/TMHMM TM helix (813-835aa), N terminus extracellular Signal Peptide Signal P .cbs.dtu.dk/services/SignalP/ yes pI pI/MW tool .cxpasy.chltools/ p1 4 .81 Molecular weight pI/MW tool .expasy.ch/tools/ 112.7 kDa Localization PSORT psort.nibb.ac.jp/ Plasma membrane PSORT II psort.nibb.ac.jp/ 67% endoplasmic reticulum Motifs Pfam .sanger.ac.uk/Pfam/ Cadherin domain Prints .biochem.ucl.ac.uk/ Cadherin domain, DNA topoiso Merase 4B, sonic hedgehog Blocks .blocks.fh8rc.org/ Cadherin domain, ribosomal protein Ll OE, ribulose biphos phate carboxylase (large chain), ornithine decarboxylase antizyme protein phosphatase 2C subfamily Table LI. Exon boundaries of transcript 109PN D4 v.1 Exon SLength 1 1 1385 1385 2 138 6 4603 3218 Table L11(a). Nucleotide sequence of transcript variant 109131 D4 v.2 (SEQ ID NO: 237) cccctttctc cccctcgqtt aagtccctcc ccctcgccat tcaaaagggc tqgctcggca 60 ctggctcctt gcagtcggcg aactgtcggg gcgggaqgag ccgtgaqcaq tagctgcact 120 cagctgcccq cgcggcaaag aggaaggcaa gccaaacaga gtgcgcagag tggcagtgcc 180 agcggcgaca caggcagcac nggcagcccg ggctgcctga atagcctcag aaacaacctc 240 agcgactccg qctgctctgc ggactgcgag ctgtggcggt agagcccgct acaqcagtcg 300 cagtctccgt ggagcgggcg gaagcctctt ttctcccttt cgtttncctc ttcattctac 360 tctaaaggca tcgttattag gaanatcctq ttgcgaataa gaaggattcc acagatcaca 420 taccggagaq gttttgcctc agctgctctc aactttgtaa tcttgtgaag aagctgacaa 480 gcttggctga ttgcagacjca ctatgaggac tgaacgacag tcjggttttaa ttcagatatt 540 tcaaqtgttg tgcgggttaa tacaacaaac tgtaacaagt gtacctggta tggacttgtt 600 gtccgggacg tacattttcg cqgtcctgct agcatgcgtg gtgttccact ctggcgccca 660 ggagaaaac tncaccatcc gagaagaaat gccagtaaaac gtcctgatng gcgacttgtt 720 gnaagacctt ancttgtcgc tcjattccaaa caagtccttg acnactgcta tgcagttcaa 780 gctagtgtac aagaccggag atgtgccact cattcgaatt gaagaggata ctggtgagat 840 cttcactact ggcgctcgca ttcjatcgtga gaaattatgt gctgrgtatcc caagcjgatga 900 gcattgcttt tatgaagtcjg aggttgccat tttgccggat gaantattta gactggttaa 960 gatacgtttt ctgatagaag atataaatqa taatgcacca ttgttcccag caaeagttat 10C20 caacatatca nttccaqaqa actcqgctat aaactctaaa tatactctcc cagcggctgt 1080 tgatcctgac ctnggaataa ncggagttca aaactacgaa ctaattaagn gtcaaancat 1140 ttttggcctc gatgtcattg aaacaccaga aggagacaag atgccacaac tgattgttca 1200 aaaggagtta gntagggang agaaggatac ctacgtgatg aaagtaaagg ttgaagatgg 1260 WO 2004/098515 PCT/US2004/013568 242 tggctttcct caaagatcca gtactgctat tttgcaagtg agtgttactg atacaaatga 1320 caaccaccca gtctttaagg agacagagat tgaagtcagt ataccagaaa atgctcctgt 1380 aggcacttca gtgacacagc tccatgccac agatgctgac ataggtgaaa atgccaagat 1440 ccacttctct ttcagcaatc tagtctccaa cattgccagg agattatttc acctcaatgc 1500 caccactgga cttatcacaa tcaaagaacc actggatagg gaagaaacac caaaccacaa 1560 gttactggtt ttggcaagtg atggtggatt gatgccagca agagcaatgg tgctggtaaa 1620 tgttacagat gtcaatgata atgtcccatc cattgacata agatacatcg tcaatcctgt 1680 caatgacaca gttgttcttt cagaaaatat tccactcaac accaaaattg ctctcataac 1740 tgtgacggat aaggatgcgg accataatgg cagggtgaca tgcttcacag atcatgaaat 1800 ccctttcaga ttaaggccag tattcagtaa tcagttcctc ctggagactg cagcatatct 1860 tgactatgag tccacaaaag aatatgccat taaattactg gctgcagatg ctggcaaacc 1920 tcctttgaat cagtcagcaa tgctcttcat caaagtgaaa gatgaaaatg acaatgctcc 1980 agttttcacc cagtctttcg taactgtttc tattcctgag aataactctc ctggcatcca 2040 gttgacgaaa gtaagtgcaa tggatgcaga cagtgggcct aatgctaaga tcaattacct 2100 gctaggccct gatgctccac ctgaattcag cctggattgt cgtacaggca tgctgactgt 2160 agtgaagaaa ctagatagag aaaaagagga taaatattta ttcacaattc tggcaaaaga 2220 taacggggta ccacccttaa ccagcaatgt cacagtcttt gtaagcatta ttgatcagaa 2280 tgacaatagc ccagttttca ctcacaatga atacaacttc tatgtcccag aaaaccttcc 2340 aaggcatggt acagtaggac taatcactgt aactgatcct gattatggag acaattctgc 2400 agttacgctc tccattttag atgagaatga tgacttcacc attgattcac aaactggtgt 2460 catccgacca aatatttcat ttgatagaga aaaacaagaa tcttacactt tctatgtaaa 2520 ggctgaggat ggtggtagag tatcacgttc ttcaagtgcc aaagtaacca taaatgtggt 2580 tgatgtcaat gacaacaaac cagttttcat tgtccctcct tccaactgtt cttatgaatt 2640 ggttctaccg tccactaatc caggcacagt ggtctttcag gtaattgctg ttgacaatga 2700 cactggcatg aatgcagagg ttcgttacag cattgtagga ggaaacacaa gagatctgtt 2760 tgcaatcgac caagaaacag gcaacataac attgatggag aaatgtgatg ttacagacct 2820 tggtttacac agagtgttgg tcaaagctaa tgacttagga cagcctgatt ctctcttcag 2880 tgttgtaatt gtcaatctgt tcgtgaatga gtcggtgacc aatgctacac tgattaatga 2940 actggtgcgc aaaagcactg aagcaccagt gaccccaaat actgagatag ctgatgtatc 3000 ctcaccaact agtgactatg tcaagatcct ggttgcagct gttgctggca ccataactgt 3060 cgttgtagtt attttcatca ctgctgtagt aagatgtcgc caggcaccac accttaaggc 3120 tgctcagaaa aacaagcaga attctgaatg ggctacccca aacccagaaa acaggcagat 3180 gataatgatg aagaaaaaga aaaagaagaa gaagcattcc cctaagaact tgctgcttaa 3240 ttttgtcact attgaagaaa ctaaggcaga tgatgttgac agtgatggaa acagagtcac 3300 actagacctt cctattgatc tagaagagca aacaatggga aagtacaatt gggtaactac 3360 acctactact ttcaagcccg acagccctga tttggcccga cactacaaat ctgcctctcc 3420 acagcctgcc ttccaaattc agcctgaaac tcccctgaat tcgaagcacc acatcatcca 3480 agaactgcct ctcgataaca cctttgtggc ctgtgactct atctccaagt gttcctcaag 3540 cagttcagat ccctacagcg tttctgactg tggctatcca gtgacgacct tcgaggtacc 3600 tgtgtccgta cacaccagac cgactgattc caggacatca actattgaaa tctgcagtga 3660 gatataactt tctaggaaca acaaaattcc attccccttc caaaaaattt caatgattgt 3720 gatttcaaaa ttaggctaag atcattaatt ttgtaatcta gatttcccat tataaaagca 3780 agcaaaaatc atcttaaaaa tgatgtccta gtgaaccttg tgctttcttt agctgtaatc 3840 tggcaatgga aatttaaaat ttatggaaga gacagtgcag cacaataaca gagtactctc 3900 atgctgtttc tctgtttgct ctgaatcaac agccatgatg taatataagg ctgtcttggt 3960 gtatacactt atggttaata tatcagtcat gaaacatgca attacttgcc ctgtctgatt 4020 gttgaataat taaaacatta tctccaggag tttggaagtg agctgaacta gccaaactac 4080 tctctgaaag gtatccaggg caagagacat ttttaagacc ccaaacaaac aaaaaacaaa 4140 accaaaacac tctggttcag tgttttgaaa atattcacta acataatatt gctgagaaaa 4200 tcatttttat tacccaccac tctgcttaaa agttgagtgg gccgggcgcg gtggctcacg 4260 cctgtaatcc cagcactttg ggaggccgag gcgggtggat cacgaggtca ggagattgag 4320 accatcctgg ctaacacggt gaaaccccat ctccactaaa aatacaaaaa attagcctgg 4380 cgtggtggcg ggcgcctgta gtcccagcta ctcgggaggc tgaggcagga gaatagcgtg 4440 aacccgggag gcggagcttg cagtgagccg agatggcgcc actgcactcc agcctgggtg 4500 acagagcaag actctgtctc aaaaagaaaa aaatgttcaa tgatagaaaa taattttact 4560 aggtttttat gttgattgta ctcatgctgt tccactcctt ttaattatta aaaagttatt 4620 tttggctggg tgtggtggct cacacctgta atcccagcac tttgggaggc cgaggtgggt 4680 ggatcacctg aggtcaggag ttcaagacca gtctggccaa cat 4723 WO 2004/098515 PCT/US2004/013568 243 Table Lill(a). Nucleotide sequence alignment of 109P1D4 v.1 (SEQ ID NO: 238) and 109P1D4 v.2 (SEQ ID NO: 239) Score = 5920 bits (3079), Expect = 0.01dentities = 3079/3079 (100%) Strand = Plus / Plus V.1 800 agtgttgtgcgggttaatacaacaaactgtaacaagtgtacctggtatggacttgttgtc 859 V.2 544 agtgttgtgcgggttaatacaacaaactgtaacaagtgtacctggtatggacttgttgtc 603 V.1 860 cgggacgtacattttcgcggtcctgctagcatgcgtggtgttccactctggcgcccagga 919 1 1 11 1 1111 IIll l llIl I 1 lill I li 111i I l Il II II I I l ll V.2 604 cgggacgtacattttcgcggtcctgctagcatgcgtggtgttccactctggcgcccagga 663 V.1 920 gaaaaactacaccatccgagaagaaatgccagaaaacgtcctgataggcgacttgttgaa 979 llil l 11l 1ili l1I II llIi1I 11Ii illi 11lli1I l I I I llI I I lI l I I I I l l I V.2 664 gaaaaactacaccatccgagaagaaatgccagaaaacgtcctgataggcgacttgttgaa 723 V.1 980 agaccttaacttgtcgctgattccaaacaagtccttgacaactgctatgcagttcaagct 1039 V.2 724 agaccttaacttgtcgctgattccaaacaagtccttgacaactgctatgcagttcaagct 783 V.1 1040 agtgtacaagaccggagatgtgccactgattcgaattgaagaggatactggtgagatctt 1099 iili I l 11 Il Ii i I l Iliil ilil l l l IllI i~ lI IlIll 1I|11 1 1 Il1 Il V.2 784 agtgtacaagaccggagatgtgccactgattcgaattgaagaggatactggtgagatctt 843 V.1 1100 cactactggcgctcgcattgatcgtgagaaattatgtgctggtatcccaagggatgagca 1159 I [ 1111111111111111111111111111ll |1Il ll iI l ill |II 111 ii iii V.2 844 cactactggcgctcgcattgatgtgagaaattatgtgctggtatcccaagggatgagca 903 V.1 1160 ttgcttttatgaagtggaggttgccattttgccggatgaaatatttagactggttaagat 1219 111 I li1 11 11 11 11 111111Il1 IlIIl l i i ll 1 Il 1llI I I II 1li 1I|| 1I|1l1I| II V.2 904 ttgcttttatgaagtggaggttgccattttgccggatgaaatatttagactggttaagat 963 V.1 1220 acgttttctgatagaagatataaatgataatgcaccattgttcccagcaacagttatcaa 1279 ii~ i l l l I lli I 1iil i l l I| |I I I Ii 1 I I 1 I llI 1 I 1i I 111 I V.2 964 acgttttctgatagaagatataaatgataatgcaccattgttcccagcaacagttatcaa 1023 V.1 1280 catatcaattccagagaactcggctataaactctaaatatactctcccagcggctgttga 1339 I ll l l l l 11 1 11I I 1i 11 1 l li | 11 I||Il I I11 l1 II I lI||I I1 I |I l V.2 1024 catatcaattccagagaactcggctataaactctaaatatactctcccagcggctgttga 1083 V.1 1340 tcctgacgtaggaataaacggagttcaaaactacgaactaattaagagtcaaaacatttt 1399 V.2 1084 tcctgacgtaggaataaacggagttcaaaactacgaactaattaagagtcaaaacatttt 1143 V.1 1400 tggcctcgatgtcattgaaacaccagaaggagacaagatgccacaactgattgttcaaaa 1459 V.2 1144 tggcctcgatgtcattgaaacaccagaaggagacaagatgccacaactgattgttcaaaa 1203 V.1 1460 ggagttagatagggaagagaaggatacctacgtgatgaaagtaaaggttgaagatggtgg 1519 V.2 1204 ggagttagatagggaagagaaggatacctacgtgatgaaagtaaaggttgaagatggtgg 1263 V.1 1520 ctttcctcaaagatccagtactgctattttgcaagtgagtgttactgatacaaatgacaa 1579 V.2 1264 ctttcctcaaagatccagtactgctattttgcaagtgagtgttactgatacaaatgacaa 1323 WO 2004/098515 PCT/US2004/013568 244 V.1 1580 ccacccagtctttaaggagacagagattgaagtcagtataccagaaaatgctcctgtagg 1639 I l l l l l l I l I l l I l l l i | I l l l I I l l i l l i l l I l l i l II l l i l I ll1 i V.2 1324 ccacccagtctttaaggagacagagattgaagtcagtataccagaaaatgctcctgtagg 1383 V.1 1640 cacttcagtgacacagctccatgccacagatgctgacataggtgaaaatgccaagatcca 1699 l il i l Illlll11 111 1 11111111 ll il llll il 1111 1 il II lll1 V.2 1384 cacttcagtgacacagctccatgccacagatgctgacataggtgaaaatgccaagatcca 1443 V.1 1700 cttctctttcagcaatctagtctccaacattgccaggagattatttcacctcaatgccac 1759 lllll I111 j l 1111111 11 1 liii 1 Illl l il ill i lill i I 1ll i V.2 1444 cttctctttcagcaatctagtctccaacattgccaggagattatttcacctcaatgccac 1503 V.1 1760 cactggacttatcacaatcaaagaaccactggatagggaagaaacaccaaaccacaagtt 1819 1111 l l l lI Il i l l l I I l i l l l l I I l i I l l || I I l l l l l l1I l 1 1 1 1 1 1 1 1 V.2 1504 cactggacttatcacaatcaaagaaccactggatagggaagaaacaccaaaccacaagtt 1563 V.1 1820 actggttttggcaagtgatggtggattgatgccagcaagagcaatggtgctggtaaatgt 1879 V.2 1564 actggttttggcaagtgatggtggattgatgccagcaagagcaatggtgctggtaaatgt 1623 V.1 1880 tacagatgtcaatgataatgtcccatccattgacataagatacatcgtcaatcctgtcaa 1939 l ill Ill1i illlllll1 i I i 11 11 1111111 ll lli l I 11111111111111 I V.2 1624 tacagatgtcaatgataatgtcccatccattgacataagatacatcgtcaatcctgtcaa 1683 V.1 1940 tgacacagttgttctttcagaaaatattccactcaacaccaaaattgctctcataactgt 1999 1 iI lI iI lII IIl IiI I li I IIII|IIlIIiIiiII li i 1 1 1 1 l1 1 1 111111II I II1 II V.2 1684 tgacacagttgttctttcagaaaatattccactcaacaccaaaattgctctcataactgt 1743 V.1 2000 gacggataaggatgcggaccataatggcagggtgacatgcttcacagatcatgaaatccc 2059 lllllll I IIi 111|1 l i I il Ii iilIliIii 11 11 1 l ii| 1 1 1 l l l I lI II lI II1Ii V.2 1744 gacggataaggatgcggaccataatggcagggtgacatgcttcacagatcatgaaatccc 1803 V.1 2060 tttcagattaaggccagtattcagtaatcagttcctcctggagactgcagcatatcttga 2119 V.2 1804 tttcagattaaggccagtattcagtaatcagttcctcctggagactgcagcatatcttga 1863 V.1 2120 ctatgagtccacaaaagaatatgccattaaattactggctgcagatgctggcaaacctcc 2179 l lIII IiiI lIII lIiI |IlI IilI I I 11 1 1 1 1 1 1 1 1 1111 l I1I I I I I 1111I 11 I V.2 1864 ctatgagtccacaaaagaatatgccattaaattactggctgcagatgctggcaaacctcc 1923 V.1 2180 tttgaatcagtcagcaatgctcttcatcaaagtgaaagatgaaaatgacaatgctccagt 2239 l i l 1 [1l 1 il li1 ll il li 111111111||111111111 111 111||1111 1111111 V.2 1924 tttgaatcagtcagcaatgctcttcatcaaagtgaaagatgaaaatgacaatgctccagt 1983 V.1 2240 tttcacccagtctttcgtaactgtttctattcctgagaataactctcctggcatccagtt 2299 V.2 1984 tttcacccagtctttcgtaactgtttctattcctgagaataactctcctggcatccagtt 2043 V.1 2300 gacgaaagtaagtgcaatggatgcagacagtgggcctaatgctaagatcaattacctgct 2359 V.2 2044 gacgaaagtaagtgcaatggatgcagacagtgggcctaatgctaagatcaattacctgct 2103 V.1 2360 aggccctgatgctccacctgaattcagcctggattgtcgtacaggcatgctgactgtagt 2419 I l l 2104Iaggclc glIII 11Ill illll IllllIII1111111llIIIII 11111111ll1 21 1 V.2 :2104 aggccctgatgctccacctgaattcagcctggattgtcgtacaggcatgctgactgtagt 2163 WO 2004/098515 PCT/US2004/013568 245 v.1 2420 gaagaaactagatagagaaaaagaggataaatatttattcacaattctggcaaaagataa 2479 V.2 2164 gaagaaactagatagagaaaaagaggataaatatttattcacaattctggcaaaagataa 2223 V.1 2480 cggggtaccacccttaaccagcaatgtcacagtctttgtaagcattattgatcagaatga 2539 lill lllll11 Il1 l11 ll lll1 l1 llllll1 llll llll II ll II l l l lll V.2 2224 cggggtaccacccttaaccagcaatgtcacagtctttgtaagcattattgatcagaatga 2283 V.1 2540 caatagcccagttttcactcacaatgaatacaacttctatgtcccagaaaaccttccaag 2599 I lI l l i i illl lllll lll1 l lllll lll I l ill1lll1 l 111 Ill Ill V.2 2284 caatagcccagttttcactcacaatgaatacaacttctatgtcccagaaaaccttccaag 2343 V.1 2600 gcatggtacagtaggactaatcactgtaactgatcctgattatggagacaattctgcagt 2659 1 1 l i ll l l l l ll l l l l l l l l l l l l l ll l ll l l l l l l ll l l i1 I ll1 l 1 I l l I l1 1 l l 1 V.2 2344 gcatggtacagtaggactaatcactgtaactgatcctgattatggagacaattctgcagt 2403 V.1 2660 tacgctctccattttagatgagaatgatgacttcaccattgattcacaaactggtgtcat 2719 V.2 2404 tacgctctccattttagatgagaatgatgacttcaccattgattcacaaactggtgtcat 2463 V.1 2720 ccgaccaaatatttcatttgatagagaaaaacaagaatcttacactttctatgtaaaggc 2779 V.2 2464 ccgaccaaatatttcatttgatagagaaaaacaagaatcttacactttctatgtaaagge 2523 V.1 2780 tgaggatggtggtagagtatcacgttcttcaagtgccaaagtaaccataaatgtggttga 2839 111 111 11| 111 111 111 111 111 IlIj i I~ l l l l lll 1 1 1 1 1 1 1 11llll V.2 2524 tgaggatggtggtagagtatcacgttcttcaagtgccaaagtaaccataaatgtggttga 2583 V.1 2840 tgtcaatgacaacaaaccagttttcattgtccctccttccaactgttcttatgaattggt 2899 V.2 2584 tgtcaatgacaacaaaccagttttcattgtccctccttccaactgttcttatgaattggt 2643 V.1 2900 tctaccgtccactaatccaggcacagtggtctttcaggtaattgctgttgacaatgacac 2959 V.2 2644 tctaccgtccactaatccaggcacagtggtctttcaggtaattgctgttgacaatgacac 2703 V.1 2960 tggcatgaatgcagaggttcgttacagcattgtaggaggaaacacaagagatctgtttgc 3019 V.2 2704 tggcatgaatgcagaggttcgttacagcattgtaggaggaaacacaagagatctgtttgc 2763 V.1 3020 aatcgaccaagaaacaggcaacataacattgatggagaaatgtgatgttacagaccttgg 3079 lii111111111111l llllll illlllllllll1l1IllII Ill Ill1ll illl V.2 2764 aatcgaccaagaaacaggcaacataacattgatggagaaatgtgatgttacagaccttgg 2823 V.1 3080 tttacacagagtgttggtcaaagctaatgaattaggacagcctgattctctcttcagtgt 3139 1lillllll11llllllllll1lllllll1l illlllll 111 li 1ll1llll il V.2 2824 tttacacagagtgttggtcaaagctaatgacttaggacagcctgattctctcttcagtgt 2883 V.1 3140 tgtaattgtcaatctgttcgtgaatgagtcggtgaccaatgctacactgattaatgaact 3199 l I ll i l l l il l l l l1l i l l l l l l l l l l l l l l 1 l i ll I l1 ll1 l l1 l l i I I1 l l l I V.2 2884 tgtaattgtcaatctgttcgtgaatgagtcggtgaccaatgctacactgattaatgaact 2943 V.1 3200 ggtgcgcaaaagcactgaagcaccagtgaccccaaatactgagatagctgatgtatcctc 3259 V.2 2944 ggtgcgcaaaagcactgaagcaccagtgaccccaaatactgagatagctgatgtatcctc 3003 WO 2004/098515 PCT/US2004/013568 246 V.1 3260 accaactagtgactatgtcaagatcctggttgcagctgttgctggcaccataactgtcgt 3319 11Il1111111 I III I IlII II 111111 lii1 I1 111l 111 I I11 l11 1| I1lii11 I V.2 3004 accaactagtgactatgtcaagatcctggttgcagctgttgctggcaccataactgtcgt 3063 V.1 3320 tgtagttattttcatcactgctgtagtaagatgtcgccaggcaccacaccttaaggctgc 3379 i11111 1 I I l i lli iIII IilIIlI II I 1 1 I 1 |111 11 11 1 IIII 111 I I I 1 V.2 3064 tgtagttattttcatcactgctgtagtaagatgtcgccaggcaccacaccttaaggctgc 3123 V.1 3380 tcagaaaaacaagcagaattctgaatgggctaccccaaacccagaaaacaggcagatgat 3439 111111111 111ll11111111111|| 1111 1 11ll 1lllll lllllllll1 Illi V.2 3124 tcagaaaaacaagcagaattctgaatgggctaccccaaacccagaaaacaggcagatgat 3183 V.1 3440 aatgatgaagaaaaagaaaaagaagaagaagcattcccctaagaacttgctgcttaattt 3499 i IiIii I l Il1l1 ii1 i l11 11 II 1 I I1 l i | IlI iII | IIii II I I1 1 I1I11 I1I1 V.2 3184 aatgatgaagaaaaagaaaaagaagaagaagcattcccctaagaacttgctgcttaattt 3243 V.1 3500 tgtcactattgaagaaactaaggcagatgatgttgacagtgatggaaacagagtcacact 3559 l 1 11il l 1 11 i l l l l l l l l l l l l l l l l l i l l l I l l l l l l | I l i l ll i l l l l l l1i V.2 3244 tgtcactattgaagaaactaaggcagatgatgttgacagtgatggaaacagagtcacact 3303 V.1 3560 agaccttcctattgatctagaagagcaaacaatgggaaagtacaattgggtaactacacc 3619 V.2 3304 agaccttcctattgatctagaagagcaaacaatgggaaagtacaattgggtaactacacc 3363 V.1 3620 tactactttcaagcccgacagccctgatttggcccgacactacaaatctgcctctccaca 3679 I111111 11llllll llllll 11 illll 1iilll l ll ll l |1 ||1111111 V.2 3364 tactactttcaagcccgacagccctgatttggcccgacactacaaatctgcctctccaca 3423 V.1 3680 gcctgccttccaaattcagcctgaaactcccctgaattcgaagcaccacatcatccaaga 3739 i I i l I ll ll ll l ll ll l1111 1|II 11111 111111111 1illlllll i V.2 3424 gcctgccttccaaattcagcctgaaactcccctgaattcgaagcaccacatcatccaaga 3483 V.1 3740 actgcctctcgataacacctttgtggcctgtgactctatctccaagtgttcctcaagcag 3799 111111 111 1111 llIi I I | llI i II 1 1 1 II Il I II I II1 il lII I1 V.2: 3484 actgcctctcgataacacctttgtggcctgtgactctatctccaagtgttcctcaagcag 3543 V.1 3800 ttcagatccctacagcgtttctgactgtggctatccagtgacgaccttcgaggtacctgt 3859 l i l l l l l l l l l l l l l l l l l l l l l l l l l l l 1 ll l l l l l l l l l l l l l l l l l l l l l l1 l l l V.2 3544 ttcagatccctacagcgtttctgactgtggctatccagtgacgaccttcgaggtacctgt 3603 V.1 3860 gtccgtacacaccagaccg 3878 l II l i I I I l l l l l i1 V.2 3604 gtccgtacacaccagaccg 3622 Table LIV(a). Peptide sequences of protein coded by 109P1D4 v.2 (SEQ ID NO: 240) MRTERQWVLI QIFQVLCGLI QQTVTSVPGM DLLSGTYIFA VLLACVVFHS GAQEKNYTIR 60 EEMPENVLIG DLLKDLNLSL IPNKSLTTAM QFKLVYKTGD VPLIRIEEDT GEIFTTGARI 120 DREKLCAGIP RDEHCFYEVE VAILPDEIFR LVKIRFLIED INDNAPLFPA TVINISIPEN 180 SAINSKYTLP AAVDPDVGIN GVQNYELIKS QNIFGLDVIE TPEGDKMPQL IVQKELDREE 240 KDTYVMKVKV EDGGFPQRSS TAILQVSVTD TNDNHPVFKE TEIEVSIPEN APVGTSVTQL 300 HATDADIGEN AKIHFSFSNL VSNIARRLFH LNATTGLITI KEPLDREETP NHKLLVLASD 360 GGLMPARAMV LVNVTDVNDN VPSIDIRYIV NPVNDTVVLS ENIPLNTKIA LITVTDKDAD 420 HNGRVTCFTD HEIPFRLRPV FSNQFLLETA AYLDYESTKE YAIKLLAADA GKPPLNQSAM 480 LFIKVKDEND NAPVFTQSFV TVSIPENNSP GIQLTKVSAM DADSGPNAKI NYLLGPDAPP 540 EFSLDCRTGM LTVVKKLDRE KEDKYLFTIL AKDNGVPPLT SNVTVFVSII DQNDNSPVFT 600 WO 2004/098515 PCT/US2004/013568 247 HNEYNFYVPE NLPRHGTVGL ITVTDPDYGD NSAVTLSILD ENDDFTIDSQ TGVIRPNISF 660 DREKQESYTF YVKAEDGGRV SRSSSAKVTI NVVDVNDNKP VFIVPPSNCS YELVLPSTNP 720 GTVVFQVIAV DNDTGMNAEV RYSIVGGNTR DLFAIDQETG NITLMEKCDV TDLGLHRVLV 780 KANDLGQPDS LFSVVIVNLF VNESVTNATL INELVRKSTE APVTPNTEIA DVSSPTSDYV 840 KILVAAVAGT ITVVVVIFIT AVVRCRQAPH LKAAQKNKQN SEWATPNPEN RQMIMMKKKK 900 KKKKHSPKNL LLNFVTIEET KADDVDSDGN RVTLDLPTDL EEQTMGKYNW VTTPTTFKPD 960 SPDLARHYKS ASPQPAFQIQ PETPLNSKHH IIQELPLDNT FVACDSISKC SSSSSDPYSV 1020 SDCGYPVTTF EVPVSVHTRP TDSRTSTIEI CSEI 1054 Table LV(e). Amino acid sequence alignment of 109P1D4 v.1 (SEQ ID NO: 241) and 109PID4 v.2 (SEQ ID NO: 242) Score 2006 bits (5197), Expect = 0.01dentities = 1012/1017 (99%), Positives = 1013/1017 (99%) V.1 1 MDLLSGTYIFAVLLACVVFHSGAQEKNYTIREEMPENVLIGDLLKDLNLSLIPNKSLTTA 60 MDLLSGTYIFAVLLACVVFHSGAQEKNYTIREEMPENVLIGDLLKDLNLSLIPNKSLTTA V.2 30 MDLLSGTYIFAVLLACVVFHSGAQEKNYTIREEMPENVLIGDLLKDLNLSLIFNKSLTTA 89 V.1 61 MQFKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIF 120 MQFKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIF V.2 90 MQFKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIF 149 V.1 121 RLVKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIK 180 RLVKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIK V.2 150 RLVKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIK 209 V.1 181 SQNIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVT 240 SQNIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVT V.2 210 SQNIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVT 269 V.1 241 DTNDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLF 300 DTNDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLF V.2 270 DTNDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLF 329 V.1 301 HLNATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYI 360 HLNATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYI V.2 330 HLNATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYI 389 V.1 361 VNPVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLET 420 VNPVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLET V.2 390 VNPVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLET 449 V.1 421 AAYLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNS 480 AAYLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNS V.2 450 AAYLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNS 509 V.1 481 PGIQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTVVKKLDREKEDKYLFTI 540 PGIQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTVVKKLDREKEDKYLFTI V.2 510 PGIQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTVVKKLDREKEDKYLFTI 569 V.1 541 LAKDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYG 600 LAKDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYG V.2 570 LAKDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYG 629 V.1 601 DNSAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVT 660 DNSAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVT V.2 630 DNSAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVT 689 V.1 661 INVVDVNDNKPVFIVPPSNCSYELVLPSTNPGTVVFQVIAVDNDTGMNAEVRYSIVGGNT 720 INVVDVNDNKPVFIVPPSNCSYELVLPSTNPGTVVFQVIAVDNDTGMNAEVRYSIVGGNT V.2 690 INVVDVNDNKPVFIVPPSNCSYELVLPSTNPGTVVFQVIAVDNDTGMNAEVRYSIVGGNT 749 V.1 721 RDLFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSVVIVNLFVNESVTNAT 780 RDLFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSVVIVNLFVNESVTNAT V.2 750 RDLFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSVVIVNLFVNESVTNAT 809 V.1 781 LINELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVVVVIFITAVVRCRQAP 840 LINELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVVVVIFITAVVRCRQAP V.2 810 LINELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVVVVIFITAVVRCRQAP 869 WO 2004/098515 PCT/US2004/013568 248 v.1 : 841 HLKAAQKNKQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDG 900 HLKAAQKNKQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDG V.2 : 870 HLKAAQKNKQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDG 929 V.1 : 901 NRVTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNSKH 960 NRVTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNSKH V.2 : 930 NRVTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDIARHYKSASPQPAFQIQPETPLNSKH 989 V.1 : 961 HIIQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRPVGIQVS 1017 HIIQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP + S V.2 : 990 HIIQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRPTDSRTS 1046 Table LII(b). Nucleotide sequence of transcript variant 109P1 D4 v.3 (SEQ ID NO: 243) ctggtggtcc agtacctcca aagatatgga atacactcct gaaatatcct gaaaactttt 60 ttttttcaga atcctttaat aagcagttat gtcaatctga aagttgctta cttgtacttt 120 atattaatag ctattcttqt ttttcttatc caaagaaaaa tcctctaatc cccttttcac 180 atgatagttg ttaccatgtt taggcattag tcacatcaac ccctctcctc tcccaaactt 240 ctcttcttca aatcaaactt tattagtccc tcctttataa tgattccttg cctcgtttta 300 tccagatcaa ttttttttca ctttgatgcc cagagctgaa gaaatggact actgtataaa 360 ttattcattg ccaagagaat aattgcattt taaacccata ttataacaaa gaataatgat 420 tatattttgt gatttgtaac aaataccctt tattttccct taactautga attaaatatt 480 ttaattattt gtattctctt taactatctt ggtatattaa agtattatct tttatatatt 540 tatcaatggt ggacactttt ataggtactc tgtgtcattt ttgatactgt aggtatctta 600 tttcatttat ctttattctt aatgtacgaa ttcataatat ttgattcaga acaaatttat 660 cactaattaa cagagtgtca attatgctaa catctcattt actgatttta atttaaaaca 720 gtttttgtta acatgcatgt ttagggttgg cttcttaata atttcttctt cctcttctct 780 ctctcctctt cttttggtca gtgttgtgcg gqttaataca acaaactgta acaagtgtac 840 ctggtatgga cttgttgtcc ggcacgtaca ttttcgcqgt cctgctagca tgcgtggtgt 900 tccactctgg cgcccaggag aaaaactaca ccatccgaga agaaatgcca gaaaacgtcc 960 tgataggcga cttgttgaaa gaccttaact tgtcgctgat tccaaacaag tccttgacaa 1020 ctgctatgca gttcaagcta gtgtacaaga ccggagatgt gccactgatt cgaattgaag 1080 aggatactgg tgagatcttc actactggcg ctcgcattga tcgtgagaaa ttatgtgctg 1140 gtatcccaag ggatgagcat tgcttttatg aagtggaggt tgccattttg ccggatgaaa 1200 tatttagact ggttaagata cgttttctga tagaagatat aaatgataat gcaccattgt 1260 tcccagcaac agttatcaac atatcaattc cagagaactc ggctataaac tctaaatata 1320 catctccagc ggctgttgat cctgacgtag gaataaacgg agttcaaaac tacgaactaa 1380 ttaagagtca aaacattttt ggcctcgatg tcattgaaac accagaagga gacaagatgc 1440 cacaactgat tgttcaaaag gagttagata gggaagagaa ggatacctac gtgatgaaag 1500 taaaggttga agatggtggc tttcctcaaa gatccagtac tgctattttg caagtgagtg 1560 ttactgatac aaatgacaac cacccagtct ttaaggagac agagattgaa gtcagtatac 1620 cagaaaatgc tcctgtaggc acttcagtga cacagctcca tgccacagat gctgacatag 1680 gtgaaaatgc caagatccac ttctctttca gcaatctagt ctccaacatt gccaggagat 1740 tatttcacct caatgccacc actggactta tcacaatcaa agaaccactg gatagggaag 1800 aaacaccaaa ccacaagtta ctggttttgg caagtgatgg tggattgatg ccagcaagag 1860 caatggtgct ggtaaatgtt acagatgtca atgataatgt cccatccatt gacataagat 1920 acatcgtcaa tcctgtcaat gacacagttg ttctttcaga aaatattcca ctcaacacca 1980 aaattgctct cataactgtg acggataagg atgcggacca taatggcagg gtgacatgct 2040 tcacagatca tgaaatccct ttcagattaa ggccagtatt cagtaatcag ttcctcctgg 2100 agactgcagc atatcttgac tatgagtcca caaaagaata tgccattaaa ttactggctg 2160 cagatgctgg caaacctcct ttgaatcagt cagcaatgct cttcatcaaa gtgaaagatg 2220 aaaatgacaa tgctccagtt ttcacccagt ctttcgtaac tgtttctatt cctgagaata 2280 actctcctgg catccagttg acgaaagtaa gtgcaatgga tgcagacagt gggcctaatg 2340 ctaagatcaa ttacctgcta ggccctgatg ctccacctga attcagcctg gattgtcgta 2400 caggcatgct gactgtagtg aagaaactag atagagaaaa agaggataaa tatttattca 2460 caattctggc aaaagataac ggggtaccac ccttaaccag caatgtcaca gtctttgtaa 2520 gcattattga tcagaatgac aatagcccag ttttcactca caatgaatac aacttctatg 2580 tcccagaaaa ccttccaagg catggtacag taggactaat cactgtaact gatcctgatt 2640 atggagacaa ttctgcagtt acgctctcca ttttagatga gaatgatgac ttcaccattg 2700 attcacaaac tggtgtcatc cgaccaaata tttcatttga tagagaaaaa caagaatctt 2760 acactttcta tgtaaaggct gaggatggtg gtagagtatc acgttcttca agtgccaaag 2820 taaccataaa tgtggttqat gtcaatgaca acaaaccagt tttcattgtc cctccttcca 2880 WO 2004/098515 PCT/US2004/013568 249 actgttctta tgaattggtt ctaccgtcca ctaatccagg cacagtggtc tttcagqtaa 2940 ttgctgttga caatgacact ggcatgaatg cagaggttcq ttacagcatt gtaggaggaa 3000 acacaagaga tctgtttgca atcgaccaag aaacaggcaa cataacattg atggagaaat 3060 gtgatgttac agaccttggt ttacacagag tgttggtcaa agctaatgac ttaggacagc 3120 ctgattctct cttcagtgtt gtaattgtca atctgttcgt gaatgagtcg gtgaccaatg 3180 ctacactgat taatgaactg gtgcgcaaaa gcactgaagc accagtgacc ccaaatactg 3240 agatagctga tgtatcctca ccaactagtg actatgtcaa gatcctggtt gcaqatgttg 3300 ctggcaccat aactgtcgtt gtagttattt tcatcactgc tgtaqtaaga tgtcgccagg 3360 caccacacct taaggctgct cagaaaaaca agcagaattc tgaatgggct accccaaacc 3420 cagaaaacag gcagatgata atgatgaaga aaaagaaaaa gaagaagaag cattccccta 3480 agaacttgct gcttaatttt gtcactattg aagaaactaa ggcagatgat gttgacagtg 3540 atggaaacag agtcacacta gaccttccta ttgatctaga agagcaaaca atgggaaagt 3600 acaattgggt aactacacct actacfttca agcccgacag ccctgatttg gcccgacact 3660 acaaatctgc ctctccacag cctgccttcc aaattcagcc tgaaactccc ctgaattcga 3720 agcaccacat catccaagaa ctgcctctcg ataacactt tgtggcctgt gactctatct 3780 ccaajtgttc ctcaagcatt tcagatccct acagcgtttc tgactgtgqc tatccagtga 3840 cgaccttcqa ggtacctgtg tccgtacaca ccagaccgcc aatgaaggag gttgtgcgat 3900 cttgcacccc catgaaagag tctacaacta tggagatctg gattcatccc caaccacagc 3960 ggaaatctga agggaaagtg jcaggaaagt cccagcggcg tgtcacattt cacctgccag 4020 aaggctctca ggaaagcagc agtgatggtg gactgggaga ccatgatgca ggcagcctta 4080 ccagcacatc tcatqgcctg ccccttggct atcctcagca ggagtacttt gatcgtgcta 4140 cacccagcaa tcgcactgaa ggggatggca actccgatcc tgaatctact ttcatacctg 4200 gactaaagaa agctgcagaa ataactgttc aaccaactgt ggaagaggcc tctgacaact 4260 gcactcaaga atgtctcatc tatggccatt ctgatgcctg ctggatgccg gcatctctgg 4320 atcattccag ctcttcgcaa gcacaggcct ctgctctatg cacagcca ccactgtcac 4380 aggcctctac tcagcaccac agcccacgag tgacacagac cattgctctc tgccacagcc 4440 ctccagtgac acagaccato gcattgtgcc acagcccacc accgatacag gtgtctgctc 4500 tccaccacag tcctcctcta gtgcaggcta ctgcacttca ccacagccca ccatcagcac 4560 aggcctcagc cctctgctac agccctcctt tagcacaggc tgctgcaatc agccacagct 4620 ctcctctgcc acaggttatt gccctccatc gtagtcaggc ccaatcatca gtcagtttgc 4680 agcaaggttg ggtgcaaggt gctgatgggc tatgctctgt tgatcaggga gtgcaaggta 4740 gtgcaacatc tcagttttac accatgtctg aaagacttca tcccagtgat gattcaatta 4800 aagtcattcc tttgacaacc itcactccac gccaacatgc cagaccgtcc agaggtgatt 4860 cccccattat ggaagaacat cccttgtaaa gctaaaatag ttacttcaaa ttttcagaaa 4920 agatgtatat agtcaaaatt taagatacaa ttccaatgag tattctgatt atcagatttg 4980 taaataacta tgtaaataga aacagatacc agaataaatc tacagctaga cccttagtca 5040 atagttaacc aaaaaattgc aatttgttta attcagaatg tgtatttaaa aagaaaagga 5100 atttaacaat ttgcatcccc ttgtacagta aggcttatca tgacagagcg cactatict 5160 gatgtacagt attttttgtt gtttttatca tcatgtgcaa tattactgat ttgtttccat 5220 gctgattgtq tggaaccagt atgtagcaaa tggaaagcct agaaatatct tattttctaa 5280 gtttaccttt agtttaccta aacttttgtt cagataacgt taaaaggtat acgtactcta 5340 ccatttttggttt tgtttgtgtgttcgtt ttg t 50 tagtgagtct cccttcaaaa tacgcagtag gtagtgtaaa tactgcttgt ttgtgtctct 5460 ctgctqtcat gttttctacc ttattccaat actatattgt tgataaaatt tgtatataca 5520 ttttcaataa agaatatgta taaactgtac agatctagat ctacaaccta tttctctact 5580 ctttagtaga gttcgagaca cagaagtgca ataactgccc taattaagca actatttgtt 5640 aaaaagggcc tctttttact ttaatagttt agtgtaaagt acatcagaaa taaagctgta 5700 tctgccattt taagcctgta gtccattatt acttgggtct ttacttctgg gaatttgtat 5760 gtaacagcct agaaaattaa aaggaggtgg atgcatccaa agcacgagtc acttaaaata 5820 tcgacggtaa actactattt tgtagagaaa ctcaggaaga tttaaatgtt gatttgacag 5880 ctcaataggc tgttaccaaa gggtgttcag taaaaataac aaatacatgt aactgtagat 5940 aaaaccatat acLaaatcta taagactaag ggatttttgt tattctagct caacttactg 6000 aagaaaacca ctaataacaa caagaatatc aggaaggaac ttttcaagaa atgtaattat 6060 aaatctacat caaacagaat tttaaggaaa aatgcagagg gagaaataag gcacatgact 6120 gcttcttgca gtcaacaaga aataccaata acacacacag aacaaaaacc atcaaaatct 6180 catatatgaa ataaaatata ttcttctaag caaagaaaca gtactattca tagaaaacat 6240 tagttttctt ctgttgtctg ttatttcctt cttgtatcct cttaactggc cattatcttg 6300 tatgtgcaca ttttataaat qtacagaaac atcaccaact Laattttctt ccatagcaaa 6360 actgagaaaa taccttgttt cagtataaca ctaaaccaag agacaattga tgtttaatgg 6420 gggcggttgg ggtggggggg ggagtcaata tctcctattg attaacttaq acatagattt 6480 tgtaatgtat aacttgatat ttaatttatg attaaactgt gtgtaaattt tgtaacataa 6540 actgtggtaa ttgcataatt tcattggtga ggatttccac tgaatattga gaaagtttct 6600 WO 2004/098515 PCT/US2004/013568 250 tttcatgtgc ccagcaggtt aagtagcgtt ttcagaatat acattattcc oatccattgt 6660 aaagttcctt aagtcatatt tgactgggcg tgcagaataa cttcttaact tttaactatc 6720 agagtttgat taataaaatt aattaatgtt ttttctcctt cgtgttgtta atqttccaag 6780 ggatttggag catactggtt ttccaggtgc atgtgaatcc cgaaggactg atgatatttg 6840 aatgtttatt aaattattat catacaaatg tgttgatatt gtggctattg ttgatgttga 6900 aaattttaaa cttggggaag attaagaaaa gaaccaatag tgacaaaaat cagtgcttcc 6960 agtagatttt agaacattct ttgcctcaaa aaacctgcaa agatgatgtg agatttttto 7020 ttgtgtttta attattttca cattttctct ctgcaaaact ttagttttct gatgatctac 7080 acacacacac acacacacac gtgcacacac acacacattt aaatgatata aaaagaagag 7140 gttgaaagat tattaaataa cttatcaggc atctcaatgg ttactatcta tgttagtgaa 7200 aatcaaatag gactcaaagt tggatatttg ggatttttct tctgacagta taatttattq 7260 agttactagg gaggttctta aatcctcata tctgcaaact tgtgacgttt tgacaccttt 7320 cctatagatg atataggaat gaaccaatac gcttttatta ccctttctaa ctctgatttt 7380 ataatcagac ttagattgtg tttagaatat taaatgactg ggcaccctct tcttggtttt 7440 taccagagag gctttgaatg gaagcaggct gagagtagcc aaagaggcaa ggggtattag 7500 cccagttatt ctcccctatg ccttccttct ctttctaagc gtccactagg tctggccttg 7560 gaaacctgtt acttctaggg cttcagatct gatgatatct ttttcatcac attacaagtt 7620 atttctctga ctgaatagac agtggtatag gttgacacag cacacaagtg gctattgtga 7680 tgtatgatgt atgtagtcct acaactgcaa aacgtcttac tgaaccaaca atcaaaaaat 7740 ggttctgttt taaaaaggat tttgtttgat ttgaaattaa aacttcaagc tgaatgactt 7800 atatgagaat aatacgttca atcaaagtag ttattctatt ttgtgtccat attccattag 7860 attgtgatta ttaattttct agctatggta ttactatatc acacttgtga gtatgtattc 7920 aaatactaag tatcttatat gctacgtgca tacacattct tttcttaaac tttacctgtg 7980 ttttaactaa tattgtgtca gtgtattaaa aattagcttt tacatatgat atctacaatg 8040 taataaattt agagagtaat tttgtgtatt cttatttact taacatttta cttttaatta 8100 tgtaaatttg gttagaaaaL aataataaat ggttagtgct attgtgtaat gqtagcagtt 8160 acaaagagcc tctgccttcc caaactaata tttatcacac atggtcatta aatgggaaaa 8220 aaatagacta aacaaatcac aaattgttca gttcttaaaa tgtaattatg tcacacacac 8280 aaaaaatcct tttcaatcct gagaaaatta aaggcgtttt actcacatgg ctatttcaac 8340 attagttttt tttgtttgtt tctttttcat ggtattactg aaggtgtgta tactccctaa 8400 tacacattta tgaaaatcta cttgtttagg cttttattta tactcttctg atttatattt 8460 tttattataa ttattatttc ttatctttct tcttttatat tttttggaaa ccaaatttat 8520 agttagttta ggtaaacttt ttattatgac cattagaaac tattttgaat gcttccaact 8580 ggctcaattg gccgggaaaa catgggagca aqagaagctg aaatatattt ctgcaagaac 8640 ctttctatat tatgtgccaa ttaccacacc agatcaattt tatgcagagg ccttaaaata 8700 ttctttcaca gtagctttct tacactaacc gtcatgtgct tttagtaaat atgattttta 8760 aaagcagttc aagttgacaa cagcagaaac agtaacaaaa aaatctgctc agaaaaatgt 8820 atgtgcacaa ataaaaaaaa ttaatggcaa ttgtttagig attgtaagtg atacttttta 8880 aagagtaaac tgtgtgaaat ttatactatc cctgcttaaa atattaagat ttttatgaaa 8940 tatgtattta tgtttgtatt gtgggaagat tcctcctctg tgatatcata cagcatctga 9000 aagtgaacag tatcccaaag cagttccaac catgctttgg aagtaagaag gttgactatt 9060 gtatggccaa ggatggcagt atgtaatcca gaagcaaact tgtattaatt gttctatttc 9120 aggttctgta ttgcatgttt tcttattaat atatattaat aaaagttat agaaat 9176 Table 1.II1(b). Nucleotide sequence alignment of 109P1 D4 v.1 (SEQ ID NO: 244) and 10951D4 v.3 (SEQ ID NO: 245) Score =7456 bits (3878), Expect =Q0.ldentities =387813878 (100%) Strand =Plus / Plus V.1 1 ctggtggtccagtacctccaaagatatggaatacactcctgaaatatcctgaaaactttt 60 V.3 1 ctggtggtccagtacctccaaagatatggaatacactcctgaaatatcctgaaaactttt 60 V.1 61 ttttttcagaatcctttaataagcagttatgtcaatctgaaattgcttacttgtacttt 120 V.3 61 ttttttcagaatcctttaataagcagttatgtcaatctgaaagttgcttacttgtacttt 120 V.1 121 atattaatagctattcttgtttttcttatccaaagaaaaatcctctaatccccttttcac 180 V.3 121 atattaatagctattcttgtttttcttatccaaagaaaaatcctctaatccccttttcaC 180 V.1 181 atgatagttgttaccatgtttaggcattagtcacatcaacccctctcctctcccaaactt 240 11111111 acacacattt11 aaatgatata11 111111 WO 2004/098515 PCT/US2004/013568 251 V.3 181 atgatagttgttaccatgtttaggcattagtcacatcaacccctctcctctcccaaactt 240 v.1: 241 ctcttcttcaaatcaaactttattagtccctcctttataatgattccttgcctcgtttta 300 V.3 241 ctcttcttcaaatcaaactttattagtccctcctttataatgattccttgcctcgtttta 300 V.1 301 tccagatcaattttttttcactttgatgcccagagctgaagaaatggactactgtataaa 360 V.3 301 tccagatcaattttttttcactttgatgcccagagctgaagaaatggactactgtataaa 360 V.1 361 ttattcattgccaagagaataattgcattttaaacccatattataacaaagaataatgat 420 V.3 361 ttattcattgccaagagaataattgcattttaaacccatattataacaaagaataatgat 420 V.1 421 tatattttgtgatttgtaacaaataccctttattttcccttaactattgaattaaatatt 480 V.3 421 tatattttgtgatttgtaacaaataccctttattttcccttaactattgaattaaatatt 480 V.1 481 ttaattatttgtattctctttaactatcttggtatattaaagtattatcttttatatatt 540 l l i llIl iIiIIlIIIIiIIIIii i I I 1I 1I 1I|I I11I 1I1 I I|II 11 1 11 1 1 11 1 1 11 1 1 I I I I II V.3 481 ttaattatttgtattctctttaactatcttggtatattaaagtattatcttttatatatt 540 V.1 541 tatcaatggtggacacttttataggtactctgtgtcatttttgatactgtaggtatctta 600 V.3 541 tatcaatggtggacacttttataggtactctgtgtcatttttgatactgtaggtatctta 600 V.1 601 tttcatttatctttattcttaatgtacgaattcataatatttgattcagaacaaatttat 660 I I i Iil IIi l 11111111111 Iii IIi iii II IIl [ l1l I I |11 1 I|1 111 I V.3 601 tttcatttatctttattcttaatgtacgaattcataatatttgattcagaacaaatttat 660 V.1 661 cactaattaacagagtgtcaattatgctaacatctcatttactgattttaatttaaaaca 720 l I 1 11 11111 11 | 1|11111| I1 1 I I II I I I V.3 661 cactaattaacagagtgtcaattatgctaacatctcatttactgattttaatttaaaaca 720 V.1 721 gtttttgttaacatgcatgtttagggttggcttcttaataatttcttcttcctcttctct 780 |1IlIIl iIIl lIIlII | |I |IIIII 1 1 11 1 11 1 1 11 ] lii 11 1 IIIII|1 1I I 1 V.3 721 gtttttgttaacatgcatgtttagggttggcttcttaataatttcttcttcctcttctct 780 V.1 781 ctctcctcttcttttggtcagtgttgtgcgggttaatacaacaaactgtaacaagtgtac 840 |1li lI iI iI I || |ll I II l I ii 1 I 11 I I I1II I||| 1 I 11111I I I Il V.3 781 ctctcctcttcttttggtcagtgttgtgcgggttaatacaacaaactgtaacaagtgtac 840 V.1 841 ctggtatggacttgttgtccgggacgtacattttcgcggtcctgctagcatgcgtggtgt 900 V.3 841 ctggtatggacttgttgtccgggacgtacattttcgcggtcctgctagcatgcgtggtgt 900 V.1 901 tccactctggcgcccaggagaaaaactacaccatccgagaagaaatgccagaaaacgtcc 960 I il II I I II II lI i I |1 i i|IIIIi I I1 II I111 I1 I I 1 111 I I I I 11111 V.3 901 tccactctggcgcccaggagaaaaactacaccatccgagaagaaatgccagaaaacgtcc 960 V.1 961 tgataggcgacttgttgaaagaccttaacttgtcgctgattccaaacaagtccttgacaa 1020 Si i i lII| |lil I I l I II 11 1 1 1 1 1 1|11 1 1 1 1 I i II 1| 1111| |1 1 || I II V.3 961 tgataggcgacttgttgaaagaccttaacttgtcgctgattccaaacaagtccttgacaa 1020 V.1 1021 ctgctatgcagttcaagctagtgtacaagaccggagatgtgccactgattcgaattgaag 1080 WO 2004/098515 PCT/US2004/013568 252 I1111111 I I lII| |I IiiiiIii I I 1 1 11 1 11 11111I 11 11i 1111l11i I lI 1i 1 Il Ii I II V.3 1021 ctgctatgcagttcaagctagtgtacaagaccggagatgtgccactgattcgaattgaag 1080 V.1 1081 aggatactggtgagatcttcactactggcgctcgcattgatcgtgagaaattatgtgctg 1140 V.3 1081 aggatactggtgagatcttcactactggcgctcgcattgatcgtgagaaattatgtgctg 1140 V.1 1141 gtatcccaagggatgagcattgcttttatgaagtggaggttgccattttgccggatgaaa 1200 V.3 1141 gtatcccaagggatgagcattgcttttatgaagtggaggttgccattttgccggatgaaa 1200 V.1 1201 tatttagactggttaagatacgttttctgatagaagatataaatgataatgcaccattgt 1260 l Ili III|lII I l I ||111 1 | iIl 11 IIIl IIIl II 11l 1 I || l1I i i l11 111 V.3 1201 tatttagactggttaagatacgttttctgatagaagatataaatgataatgcaccattgt 1260 V.1 1261 tcccagcaacagttatcaacatatcaattccagagaactcggctataaactctaaatata 1320 V.3 1261 tcccagcaacagttatcaacatatcaattccagagaactcggctataaactctaaatata 1320 V.1 1321 ctctcccagcggctgttgatcctgacgtaggaataaacggagttcaaaactacgaactaa 1380 111 1l1I 11|I 111I 11I111l 1 1111l 111 l ll I I llI I I I 1111 Il 11 IIl V.3 1321 ctctcccagcggctgttgatcctgacgtaggaataaacggagttcaaaactacgaactaa 1380 V.1 1381 ttaagagtcaaaacatttttggcctcgatgtcattgaaacaccagaaggagacaagatgc 1440 V.3 1381 ttaagagtcaaaacatttttggcctcgatgtcattgaaacaccagaaggagacaagatgc 1440 V.1 1441 cacaactgattgttcaaaaggagttagatagggaagagaaggatacctacgtgatgaaag 1500 V.3 1441 cacaactgattgttcaaaaggagttagatagggaagagaaggatacctacgtgatgaaag 1500 V.1 1501 taaaggttgaagatggtggctttcctcaaagatccagtactgctattttgcaagtgagtg 1560 IIIiII 11 l i lllii ii 111 111| 1 111I1 1 Il lIi|I111II ii II11l|I 1 1 I1111 V.3 1501 taaaggttgaagatggtggctttcctcaaagatccagtactgctattttgcaagtgagtg 1560 V.1 1561 ttactgatacaaatgacaaccacccagtctttaaggagacagagattgaagtcagtatac 1620 I I l IIllI| Il Ilil I I I |||Il 1 I I 1l I il 1l1IIl I 1l1IIl11I1I 1 IlI1I V.3 1561 ttactgatacaaatgacaaccacccagtctttaaggagacagagattgaagtcagtatac 1620 V.1 1621 cagaaaatgctcctgtaggcacttcagtgacacagctccatgccacagatgctgacatag 1680 111111I1l i I iiiiiI 11 i i IlIi I I ii i 11I 1 11I 1 I 1I I V.3 1621 cagaaaatgctcctgtaggcacttcagtgacacagctccatgccacagatgctgacatag 1680 V.1 1681 gtgaaaatgccaagatccacttctctttcagcaatctagtctccaacattgccaggagat 1740 V.3 1681 gtgaaaatgccaagatccacttctctttcagcaatctagtctccaacattgccaggagat 1740 V.1 1741 tatttcacctcaatgccaccactggacttatcacaatcaaagaaccactggatagggaag 1800 V.3 1741 tatttcacctcaatgccaccactggacttatcacaatcaaagaaccactggatagggaag 1800 V.1 1801 aaacaccaaaccacaagttactggttttggcaagtgatggtggattgatgccagcaagag 1860 V.3 1801 aaacaccaaaccacaagttactggttttggcaagtgatggtggattgatgccagcaagag 1860 WO 2004/098515 PCT/US2004/013568 253 V.1 1861 caatggtgctggtaaatgttacagatgtcaatgataatgtcccatccattgacataagat 1920 1111Ilill I II I Il lil 1 I l I I I 1l I 11ll I III1 I l l lil ill I II 1 | | Il V.3 1861 caatggtgctggtaaatgttacagatgtcaatgataatgtcccatccattgacataagat 1920 V.1 1921 acatcgtcaatcctgtcaatgacacagttgttctttcagaaaatattccactcaacacca 1980 V.3 1921 acatcgtcaatcctgtcaatgacacagttgttctttcagaaaatattccactcaacacca 1980 V.1 1981 aaattgctctcataactgtgacggataaggatgcggaccataatggcagggtgacatgct 2040 1111 |||11111 I i i111111111ll l ll l l l l ll ll ll l l l ill V.3 1981 aaattgctctcataactgtgacggataaggatgcggaccataatggcagggtgacatgct 2040 V.1 2041 tcacagatcatgaaatccctttcagattaaggccagtattcagtaatcagttcctcctgg 2100 1i i111 111 I 1II11ll 11l1||llll 1lllll il 11 l l llll lli Il1 Ill lll V.3 2041 tcacagatcatgaaatccctttcagattaaggccagtattcagtaatcagttcctcctgg 2100 V.1 2101 agactgcagcatatcttgactatgagtccacaaaagaatatgccattaaattactggctg 2160 V.3 2101 agactgcagcatatcttgactatgagtccacaaaagaatatgccattaaattactggctg 2160 V.1 2161 cagatgctggcaaacctcctttgaatcagtcagcaatgctcttcatcaaagtgaaagatg 2220 V.3 2161 cagatgctggcaaacctcctttgaatcagtcagcaatgctcttcatcaaagtgaaagatg 2220 V.1 2221 aaaatgacaatgctccagttttcacccagtctttcgtaactgtttctattcctgagaata 2280 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 | | | 1 1 l l l i l l l l l l l l l l l 1 1 1 l l 1 i l l l i l V.3 2221 aaaatgacaatgctccagttttcacccagtctttcgtaactgtttctattcctgagaata 2280 V.1 2281 actctcctggcatccagttgacgaaagtaagtgcaatggatgcagacagtgggcctaatg 2340 V.3 2281 actctcctggcatccagttgacgaaagtaagtgcaatggatgcagacagtgggcctaatg 2340 V.1 2341 ctaagatcaattacctgctaggccctgatgctccacctgaattcagcctggattgtcgta 2400 V.3 2341 ctaagatcaattacctgctaggccctgatgctccacctgaattcagcctggattgtcgta 2400 V.1 2401 caggcatgctgactgtagtgaagaaactagatagagaaaaagaggataaatatttattca 2460 I I l l l l I l ii I l l I | 1 | l I 11 l l I1ll l | I l I l i l I l I I l I1 1 V.3 2401 caggcatgctgactgtagtgaagaaactagatagagaaaaagaggataaatatttattca 2460 V.1 2461 caattctggcaaaagataacggggtaccacccttaaccagcaatgtcacagtctttgtaa 2520 V.3 2461 caattctggcaaaagataacggggtaccacccttaaccagcaatgtcacagtctttgtaa 2520 V.1 2521 gcattattgatcagaatgacaatagcccagttttcactcacaatgaatacaacttctatg 2580 V.3 2521 gcattattgatcagaatgacaatagcccagttttcactcacaatgaatacaacttctatg 2580 V.1 2581 tcccagaaaaccttccaaggcatggtacagtaggactaatcactgtaactgatcctgatt 2640 lI I I I I I IIiIllII I i ii 1 I|I1 1 l1 Il l1 I I| |I I1 l I II|I11 1 Il I1 V.3 2581 tcccagaaaaccttccaaggcatggtacagtaggactaatcactgtaactgatcctgatt 2640 V.1 2641 atggagacaattctgcagttacgctctccattttagatgagaatgatgacttcaccattg 2700 V.3 2641 atggagacaattctgcagttacgctctccattttagatgagaatgatgacttcaccattg 2700 WO 2004/098515 PCT/US2004/013568 254 V.1 2701 attcacaaactggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatctt 2760 liI I I| |Il 111|1 11I11111 I1l I1 lii lF111 111111111111| lI lI I1 II1II1 I V.3 2701 attcacaaactggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatctt 2760 V.1 2761 acactttctatgtaaaggctgaggatggtggtagagtatcacgttcttcaagtgccaaag 2820 l II I IiIl li ii II |1 lI 1 11I II 1 l I I I |111 l i i I V.3 2761 acactttctatgtaaaggctgaggatggtggtagagtatcacgttcttcaagtgccaaag 2820 V.1 2821 taaccataaatgtggttgatgtcaatgacaacaaaccagttttcattgtccctccttcca 2880 I11 I I I I I I 1i 1 ii 1 1 111 iI 1ii 11 1 I 1 i 1 l 11I Il 1II I 11I I 1 I I lI I V.3 2821 taaccataaatgtggttgatgtcaatgacaacaaaccagttttcattgtccctccttcca 2880 v.1 2881 actgttcttatgaattggttctaccgtccactaatccaggcacagtggtctttcaggtaa 2940 V.3 2881 actgttcttatgaattggttctaccgtccactaatccaggcacagtggtctttcaggtaa 2940 V.1 2941 ttgctgttgacaatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaa 3000 111I1I111I1 I li 1 11111 l l 1 I 1111i iI 11 1 |11 I I I IlIIIl F F i V.3 2941 ttgctgttgacaatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaa 3000 V.1 3001 acacaagagatctgtttgcaatcgaccaagaaacaggcaacataacattgatggagaaat 3060 V.3 3001 acacaagagatctgtttgcaatcgaccaagaaacaggcaacataacattgatggagaaat 3060 V.1 3061 gtgatgttacagaccttggtttacacagagtgttggtcaaagctaatgacttaggacagc 3120 V.3 3061 gtgatgttacagaccttggtttacacagagtgttggtcaaagctaatgacttaggacagc 3120 V.1 3121 ctgattctctcttcagtgttgtaattgtcaatctgttcgtgaatgagtcggtgaccaatg 3180 V.3 3121 ctgattctctcttcagtgttgtaattgtcaatctgttcgtgaatgagtcggtgaccaatg 3180 V.1 3181 ctacactgattaatgaactggtgcgcaaaagcactgaagcaccagtgaccccaaatactg 3240 V.3 3181 ctacactgattaatgaactggtgcgcaaaagcactgaagcaccagtgaccccaaatactg 3240 V.1 3241 agatagctgatgtatcctcaccaactagtgactatgtcaagatcctggttgcagctgttg 3300 V.3 3241 agatagctgatgtatcctcaccaactagtgactatgtcaagatcctggttgcagctgttg 3300 V.1 3301 ctggcaccataactgtcgttgtagttattttcatcactgctgtagtaagatgtcgccagg 3360 V.3 3301 ctggcaccataactgtcgttgtagttattttcatcactgctgtagtaagatgtcgccagg 3360 V.1 3361 caccacaccttaaggctgctcagaaaaacaagcagaattctgaatgggctaccccaaacc 3420 V.3 3361 caccacaccttaaggctgctcagaaaaacaagcagaattctgaatggctaccccaaacc 3420 V.1 3421 cagaaaacaggcagatgataatgatgaagaaaaagaaaaagaagaagaagcattccccta 3480 V.3 3421 cagaaaacaggcagatgataatgatgaagaaaaagaaaaagaagaagaagcattccccta 3480 V.1 3481 agaacttgctgcttaattttgtcactattgaagaaactaaggcagatgatgttgacagtg 3540 V.3 38 1 1 agaa I ig I 1 i IFIFI |111 FFt I i I I i I I I 1F 1 | I I 3540 V.3 :3481 agaacttgctgcttaattttgtcactattgaagaaactaaggcagatgatgttgacagtg 3540 WO 2004/098515 PCT/US2004/013568 255 V.1 3541 atggaaacagagtcacactagaccttcctattgatctagaagagcaaacaatgggaaagt 3600 1 11 1 1 1 1 111 lII lI 11I11li i |11|I l i i 1I 11l 11 l ii i II lI11IIl|I V.3 3541 atggaaacagagtcacactagaccttcctattgattagaagagcaaacaatgggaaagt 3600 V.1 3601 acaattgggtaactacacctactactttcaagcccgacagccetgatttggcccgacact 3660 IlI I i I 11 l11111 1 ll I Il 1 1 llIlII I i 1 II I I I II Il I I11 11 V.3 3601 acaattgggtaactacacctactactttcaagcccgacagccctgatttggcccgacact 3660 V.1 3661 acaaatctgcctctccacagcctgccttccaaattcagcctgaaactcccctgaattcga 3720 lI ill 1i1111ll 1 1 1 111 1 llI l l Ill !11111 i i111111|I V.3 3661 acaaatctgcctctccacagcctgccttccaaattcagcctgaaactcccctgaattcga 3720 V.1 3721 agcaccacatcatccaagaactgcctctcgataacacctttgtggcctgtgactctatct 3780 I I 11 liII |111 1 11 1 1 11 1 II 1 11I 1|| I|IlIIII 11 Il I1I V.3 3721 agcaccacatcatccaagaactgccttcgataacacctttgtggcctgtgactctatct 3780 V.1 3781 ccaagtgttcctcaagcagttcagatccctacagcgtttctgactgtggctatccagtga 3840 IllI Ill1 ll Il|II1 111111111111 ||Il11IIII 1lllllIIII1llllll1 lIII V.3 3781 ccaagtgttcctcaagcagttcagatccctacagcgtttctgactgtggctatccagtga 3840 V.1 3841 cgaccttcgaggtacctgtgtccgtacacaccagaccg 3878 ill illl1 Il|III|11111111111||11111IllllI V.3 3841 cgaccttcgaggtacctgtgtccgtacacaccagaccg 3878 Table LIV(b). Peptide sequences of protein coded by 109P1D4 v.3 (SEQ ID NO: 246) MDLLSGTYIF AVLLACVVFH SGAQEKNYTI REEMPENVLI GDLLKDLNLS LIPNKSLTTA 60 MQFKLVYKTG DVPLIRIEED TGEIFTTGAR IDREKLCAGI PRDEHCFYEV EVAILPDEIF 120 RLVKIRFLIE DINDNAPLFP ATVINISIPE NSAINSKYTL PAAVDPDVGI NGVQNYELIK 180 SQNIFGLDVI ETPEGDKMPQ LIVQKELDRE EKDTYVMKVK VEDGGFPQRS STAILQVSVT 240 DTNDNHPVFK ETEFIEVSIPE NAPVGTSVTQ LHATDADIGE NAKIHFSFSN LVSNIARRLF 300 HLNATTGLIT IKEPLDREET PNHKLLVLAS DGGLMPARAM VLVNVTDVND NVPSIDIKYI 360 VNPVNDTVVL SENIPLNTKI ALITVTDKDA DHNGRVTCFT DHEIPFRLRP VFSNQFLLET 420 AAYLDYESTK EYAIKLLAAD AGKPPLNQSA MLFIKVKDEN DNAPVFTQSF VTVSIPENNS 480 PGIQLTKVSA MDADSGPNAK INYLLGPDAP PEFSLDCRTG MLTVVKKLDR EKEDKYLFTI 540 LAKDNGVPPL TSNVTVFVSI IDQNDNSPVF THNEYNFYVP ENLPRHGTVG LITVTDPDYG 600 DNSAVTLSIL DENDDFTIDS QTGVIRPNIS FDREKQESYT FYVKAEDGGP VSRSSSAKVT 660 INVVDVNDNK PVFIVPPSNC SYELVLPSTN PGTVVFQVIA VDNDTGMNAE VRYSIVGGNT 720 RDLFAIDQET GNITLMEKCD VTDLGLHRVL VKANDLGQPD SLFSVVIVNL FVNESVTNAT 780 LINELVRKST EAPVTPNTEI ADVSSPTSDY VKILVAAVAG TITVVVVIFI TAVVRCRQAP 840 HLKAAQKNKQ NSEWATPNPE NRQMIMMKKK KKKKKHSPKN LLLNFVTIEE TKADDVDSDG 900 NRVTLDLPID LEEQTMGKYN WVTTPTTFKP DSPDLARHYK SASPQPAFQI QPETPLNSKH 960 HIIQELPLDN TFVACDSISK CSSSSSDPYS VSDCGYPVTT FEVPVSVHTR PPMKEVVRSC 1020 TPMKESTTME IWIHPQPQRK SEGKVAGKSQ RRVTFHLPEG SQESSSDGGL GDHDAGSLTS 1080 TSHGLPLGYP QEEYFDRATP SNRTEGDGNS DPESTFIPGL KKAAEITVQP TVEEASDNCT 1140 QECLIYCHSD ACWMPASLDH SSSSQAQASA LCHSPPLSQA STQHHSPRVT QTIALCHSPP 1200 VTQTIALCHS PPPIQVSALH HSPPLVQATA LHHSPPSAQA SALCYSPPLA QAAAISHSSP 1260 LPQVIALHRS QAQSSVSLQQ GWVQGADGLC SVDQGVQGSA TSQFYTMSER LHFSDDSIKV 1320 IPLTTFTPRQ QARPSRGDSP IMELHPL 1347 Table LV(b). Amino acid sequence alignment of 1 09P1 D4 v.1 (SEQ ID NO: 247) and 1 09131 D4 v.3 (SEQ ID NO: 248) Score =2005 bits (5195), Expect = 0.ldentities = 1011/1011 (100%), Positives =10 11/1011 (100%) V.1 1 MDLLSGTYIFAVLLACVVFHSGAQEKNYTIREEM4PENVLIGDLJA DLNLSLIPNKSLTTA 60 MDLLSGTYI FAVLLACVVFHSGAQEKNYTIREEMFENVLIGDLLKDLNLSLI PNKSLTTA V.3 1 MDLLSGTYIFAVLLACVVFHSGAQEKNYTIR5EEMPENVLIGDLLKDLNLSLIPNKSLTTA 60 V.1 61 MQ5 LVYKTGDVPLIRIEEDTGEIFTTG.ARIDREKLCAGIPRDEHC8YEVEVAILPDEIF 120 WO 2004/098515 PCT/US2004/013568 256 MQFKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIF V.3 61 MQFKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIF 120 V.1 121 RLVKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIK 180 RLVKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIK V.3 121 RLVKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIK 180 V.1 181 SQNIFGLDVIETPE.GDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVT 240 SQNIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVT V.3 181 SQNIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVT 240 V.1 241 DTNDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLF 300 DTNDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLF V.3 241 DTNDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLF 300 V.1 301 HLNATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYI 360 HLNATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYI V.3 301 HLNATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYI 360 V.1 361 VNPVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLET 420 VNPVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLET V.3 361 VNPVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLET 420 V.1 421 AAYLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNS 480 AAYLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNS V.3 421 AAYLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNS 480 V.1 481 PGIQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTVVKKLDREKEDKYLFTI 540 PGIQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTVVKKLDREKEDKYLFTI V.3 481 PGIQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTVVKKLDREKEDKYLFTI 540 V.1 541 LAKDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYG 600 LAKDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYG V.3 541 LAKDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYG 600 V.1 601 DNSAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVT 660 DNSAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVT V.3 601 DNSAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVT 660 V.1 661 INVVDVNDNKPVFIVPPSNCSYELVLPSTNPGTVVFQVIAVDNDTGMNAEVRYSIVGGNT 720 INVVDVNDNKPVFIVPPSNCSYELVLPSTNPGTVVFQVIAVDNDTGMNAEVRYSIVGGNT V.3 661 INVVDVNDNKPVFIVPPSNCSYELVLPSTNPGTVVFQVIAVDNDTGMNAEVRYSIVGGNT 720 V.1 721 RDLFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSVVIVNLFVNESVTNAT 780 RDLFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSVVIVNLFVNESVTNAT V.3 721 RDLFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSVVIVNLFVNESVTNAT 780 V.1 781 LINELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVVVVIFITAVVRCRQAP 840 LINELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVVVVIFITAVVRCRQAP V.3 781 LINELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVVVVIFITAVVRCRQAP 840 V.1 841 HLKAAQKNKQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDG 900 Table LII(c). Nucleotide sequence of transcript variant 109P1D4 v.4 (SEQ ID NO: 249) ctggtggtcc agtacctcca aagatatgga atacactcct gaaatatcct gaaaactttt 60 ttttttcaga atcctttaat aagcagttat gtcaatctga aagttgctta cttgtacttt 120 atattaatag ctattcttgt ttttcttatc caaagaaaaa tcctctaatc cccttttcac 180 atgatagttg ttaccatgtt taggcattag tcacatcaac ccctctcctc tcccaaactt 240 ctcttcttca aatcaaactt tattagtccc tcctttataa tgattccttg cctcgtttta 300 tccagatcaa ttttttttca ctttgatgcc cagagctqaa gaaatggaot actgtataaa 360 ttattcattg ccaagagaat aattgoattt taaacccata ttataacaaa gaataatgat 420 tatattttgt gatttgtaac aaataccctt tattttccct taactattga attaaatatt 40 ttaattattt gtattctctt taactatctt ggtatattaa agtattatct tttatatatt 540 tatcaatggt ggacactttt ataggtactc tgtgtcattt ttgatactgt aggtatctta 600 tttcatttat ctttattctt aatgtacgaa ttcataatat ttgattcaga acaaatttat 660 cactaattaa cagagtgtca attatgctaa catctcattt actgatttta atttaaaaca 720 gtttttgtta acatgcatgt ttagggttgg cttcttaata atttcttctt cctcttctct 780 WO 2004/098515 PCT/US2004/013568 257 ctctcctctt cttttggtca gtgttgtgcg ggttaataca acaaactgta acaagtgtac 840 ctggtatgga cttgttgtcc gggacgtaca ttttcgcggt cctgctagca tgcgtggtgt 900 tccactctgg cgcccaggag aaaaactaca ccatccgaga agaaatgcca gaaaacgtcc 960 tgataggcga cttgttgaaa gaccttaact tgtcgctgat tccaaacaag tccttgacaa 1020 ctgctatgca gttcaagcta gtgtacaaga ccggagatgt gccactgatt cgaattgaag 1080 aggatactgg tgagatcttc actactggcg ctcgcattga tcgtgagaaa ttatgtgotg 1140 gtatcccaag ggatgagcat tgcttttatg aagtggaggt tgccattttg ccggatgaaa 1200 tatttagact ggttaagata cgttttctga tagaagatat aaatgataat gcaccattgt 1260 tcccagcaac agttatcaac atatcaattc cagagaactc ggctataaac tctaaatata 1320 ctctcccagc ggctgttgat cctgacgtag gaataaacgg agttcaaaac tacgaactaa 1380 ttaagagtca aaacattttt ggcctcgatg tcattgaaac accagaagga gacaagatgc 1440 cacaactgat tgttcaaaag gagttagata gggaagagaa ggatacctac gtgatgaaag 1500 taaaggttga agatggtggc tttcctcaaa gatccagtac tgctattttg caagtgagtg 1560 ttactgatac aaatgacaac cacccagtct ttaaqgagaa agagattgaa gtcagtatac 1620 cagaaaatgc tcctgtaggc acttcagtga cacagctcca tgccacagat gctgacatag 1680 gtgaaaatge caagatccac ttctctttca gcaatctagt ctccaacatt gocaggagat 1740 tatttcacct caatgccacc actggactta tcacaatcaa agaaccactg gatagggaag 1800 aaacaccaaa ccacaagtta ctggttttgg caagtgatgg tggattgatg ccagcaagag 1860 caatggtgct ggtaaatgt acagatgtca atgataatgt cccatccatt gacataagat 1920 acatcgtcaa tcctgtcaat gacacagttg ttctttcaga aaatattcca ctcaacacca 1980 aaattgctct cataactgtg acggataagg atgcggacca taatggcagg gtgacatgct 2040 tcacagatca tgaaatccct ttcagattaa ggccagtatt cagtaatcag ttcctcctgg 2100 agactgcagc atatcttgac tatgagtcca caaaagaata tgccattaaa ttactggctg 2160 cagatgctgg caaacctcct ttgaatcagt cagcaatgct cttcatcaaa gtgaaagatg 2220 aaaatgacaa tgctccagtt ttcacccagt ctttcgtaac tgtttctatt cctgagaata 2280 actctcctgg catccagttg acgaaagtaa gtgcaatgga tgcagacagt gggcctaatg 2340 ctaagatcaa ttacctgcta ggccctgatg ctccacctqa aftcagcctg gattgtcgta 2400 caggcatgct gactgtagtg aagaaactag atagagaaaa agaggataaa tatttattca 2460 caattctggc aaaagataac ggggtaccac ccttaaccag caatgtcaca gtctttgtaa 2520 gcattattga tcagaatgac aatagcccag ttttcactca caatgaatac aacttctatg 2580 tcccagaaaa ccttccaagg catggtacag taggactaat cactgtaact gatcctgatt 2640 atggagacaa ttctgcagtt acgctctcca ttttagatga gaatgatgac ttcaccattg 2700 attcacaaac tggtgtcatc cgaccaaata tttcatttga tagagaaaaa caagaatctt 2760 acactttcta tgtaaaggct gaggatggtg gtagagtatc acgttcttca agtgccaaag 2820 taaccataaa tgtggttgat gtcaatgaca acaaaccagt tttcattgtc cctccttcca 2880 actgttctta tgaattggtt ctaccgtcca ctaatccagg cacagtggtc tttcaggtaa 2940 ttgctgttga caatgacact ggcatgaatg cagaggttcg ttacagcatt gtaggaggaa 3000 acacaagaga tctgtttgca atcgaccaag aaacaggcaa cataacattg atggagaaat 3060 gtgatgttac agaccttggt ttacacagag tgttggtcaa agctaatgac ttaggacagc 3120 ctgattctct cttcagtgtt gtaattgtca atctgttcgt gaatgagtcg gtgaccaatg 3180 ctacactgat taatgaactg gtgcgcaaaa gcactgaagc accagtgacc ccaaatactg 3240 agatagctga tgtatcctca ccaactagtg actatgtcaa gatcctggtt gcagctgttg 3300 ctggcaccat aactgtcgtt gtagttattt tcatcactgc tgtagtaaqa tgtcgccagg 3360 caccacacct taaggctgct cagaaaaaca agcagaattc tgaatgggct accccaaacc 3420 cagaaaacag gcagatgata atgatgaaga aaaagaaaaa gaagaagaag cattccccta 3480 agaacttgct gcttaatttt gtcactattg aagaaactaa ggcagatgat gttgacagtg 3540 atggaaacag agtcacacta gaccttccta ttgatctaga agagcaaaca atgggaaagt 3600 acaattgggt aactacacct actactttca agcccgacag ccctgatttg gcccgacact 3660 acaaatctgc ctctccacag cctgccttcc aaattcagcc tgaaactccc ctgaattcga 3720 agcaccacat catccaagaa ctgcctctcg ataacacctt tgtggcctgt gactctatct 3780 ccaagtgttc ctcaagcagt tcagatccct acagcgtttc tgactgtggc tatccagtca 3840 cgaccttcga ggtacctgtg tccgtacaca ccagaccgcc aatgaaggag gttgtgcgat 3900 cttgcacccc catgaaagag tctacaacta tggagatctg gattcatccc caaccacagt 3960 cccagcggcg tgtcacattt cacctgccag aaggctctca ggaaagcagc agtgatggtg 4020 gactgggaga ccatgatgca ggcagcctta ccagcacatc tcatggcctg ccccttggct 4080 atcctcagga ggagtacttt gatcgtgcta cacccagcaa tcgcactgaa ggggatggca 4140 actccgatcc tgaatctact ttcatacctg gactaaagaa agctgcagaa ataactgttc 4200 aaccaactgt ggaagaggcc tctgacaact gcactcaaga atgtctcatc tatggccatt 4260 ctgatgcctg ctggatgccg gcatctctgg atcattocag ctcttcgcaa gcacaggcct 4320 ctgctctatg ccacagccca ccactgtcac aggcctctac tcagcaccac agcccacgag 4380 tgacacagac cattgctctc tgccacagcc ctccagtgac acagaccatc gcattgtgcc 4440 acagcccacc accgatacag gtgtctgctc tccaccacag tcctcctcta gtgcaggcta 4500 WO 2004/098515 PCT/US2004/013568 258 ctgcacttca ccacagccca ccatcagcac aggcctcagc cctctqctac agccctcctt 4560 tagcacaggc tgctgcaatc agccacagct ctcctctgcc acaggttatt gccctccatc 4620 gtagtcaggc ccaatcatca gtcagtttgc agcaaggttg ggtgcaaggt gctgatggqc 4680 tatgctctgt tgatcaggga gtgcaaggta gtgcaacatc tcagttttac accatgtctg 4740 aaagacttca tcccagtgat qattcaatta aagtcattcc tttgacaacc ttcactccac 4800 gccaacaggc cagaccgtcc agaggtgatt cccccattat ggaagaacat cccttgtaaa 4860 gctaaaatag ttacttcaaa ttttcagaaa agatgtatat agtcaaaatt taagatacaa 4920 ttccaatgag tattctgatt atcagatttg taaataacta tgtaaataga aacagatacc 4980 agaataaatc tacagctaga cccttagtca atagttaacc aaaaaattgc aatttgttta 5040 attcagaatg tgtatttaaa aagaaaagga atttaacaat ttgcatcccc ttgtacagta 5100 aggcttatca tgacagagcg cactatttct gatgtacagt attttttgtt gtttttatca 5160 tcatgtgcaa tattactgat ttgtttccat gctgattgtg tggaaccagt atgtagcaaa 5220 tggaaagcct agaaatatct tattttctaa gtttaccttt agtttaccta aacttttgtt 5280 cagataacgt taaaaggtat acgtactcta gccttttttt gggctttctt ttqattttt 5340 gtttgttgtt ttcagttttt ttgttqttgt tagtgagtct cccttcaaaa tacqcagtag 5400 gtagtgtaaa tactgcttgt ttgtgtctct ctgctgtcat gttttctacc ttattccaat 5460 actatattgt tgataaaatt tgtatataca ttttcaataa agaatatgta taaactgtac 5520 agatctagat ctacaaccta tttctctact ctttagtaga gttcgagaca cagaagtgca 5580 ataactgccc taattaagca actatttgtu aaaaagggcc tctttttact ttaatagttt 5640 agtgtaaagt acatcagaaa taaagctgta tctgccattt taagcctgta gtccattatt 5700 acttgggtct ttacttctgg gaatttgtat gtaacagcct agaaaattaa aaggaggtgg 5760 atgcatccaa agcacgagtc acttaaaata tcgacggtaa actactattt tgtagagaaa 5820 ctcaggaaga tttaaatgtt gatttgacag ctcaataggc tgttaccaaa gggtgttcag 5880 taaaaataac aaatacatgt aactgtagat aaaaccatat actaaatcta taagactaag 5940 ggatttttgt tattctagct caacttactg aagaaaacca ctaataacaa caagaatatc 6000 aggaaggaac ttttcaagaa atctaattat aaatctacat caaacagaat Lttaaggaaa 6060 aatgcagagg gagaaataag gcacatgact gcttcttgca gtcaacaaga aataccaata 6120 acacacacag aacaaaaacc atcaaaatct catatatqaa ataaaatata ttcttctaag 6180 caaagaaaca gtactattca tagaaaacat tagttttctt ctgttgtctg ttatttcctt 6240 cttgtatcct cttaactggc cattatcttg tatgtgcaca ttttataaat gtacagaaac 6300 atcaccaact taattttctt ccatagcaaa actgagaaaa taccttgttt cagtataaca 6360 ctaaaccaag agacaattga tgtttaatgg gggcggttgg ggtgggqggg ggagtcaata 6420 tctcctattg attaacttag acatagattt tgtaatgtat aacttgatat ttaatttatg 6480 attaaactgt gtgtaaattt tgtaacataa actgtggtaa ttgcataatt tcattggtga 6540 ggatttccac tgaatattga gaaagtttct tttcatgtgc ccagcaggtt aagtagcgtt 6600 ttcagaatat acattattcc catccattgt aaagttcctt aagtcatatt tgactgggcg 6660 tgcagaataa cttcttaact tttaactatc agagtttgat taataaaatt aattaatgtt 6720 ttttctcctt cgtgttgtta atgttccaag ggatttggag catactggtt ttccaggtgc 6780 atgtgaatcc cgaaggactg atgatatttg aatgtttatt aaattattat catacaaatg 6840 tgttgatatt gtggctattg ttgatgttga aaattttaaa cttggggaag attaagaaaa 6900 gaaccaatag tgacaaaaat cagtgctcc agtagatttt agaacattct ttgcctcaaa 6960 aaacctgcaa agatgatgtg agattttttc ttgtgtttta attattttca cattttctct 7020 ctgcaaaact ttagttttct gatgatctac acacacacac acacacacac gtgcacacac 7080 acacacattt aaatgatata aaaagaagag gttgaaaat tattaaataa cttatcaggc 7140 atctcaatgg ttactatcta tgttagtgaa aatcaaatag gactcaaagt tggatatttg 7200 ggatttttct tctgacagta taatttattg agttactagg gaggttctta aatcctcata 7260 tctggaaact tgtgacgttt tgacaccttt cctatagatg atataggaat gaaccaatac 7320 gcttttatta ccctttctaa ctctgatttt ataatcagac ttagattgtg tttagaatat 7380 taaatgactg ggcaccctct tcttggtttt taccagagag gctttgaatg gaagcaggct 7440 gagagtagcc aaagaggcaa ggggtattag cccagttatt ctcccctatg ccttccttct 7500 ctttctaagc gtccactagg tctggccttg gaaacctgtt acttctaggg cttcagatct 7560 gatgatatct ttttcatcac attacaagtt atttctctga ctgaatagac agtggtatag 7620 gttgacacag cacacaagtg gctattgtga tgtatgatgt atgtagtcct acaactgcaa 7680 aacgtcttac tgaaccaaca atcaaaaaat ggttctgttt taaaaaggat tttgtttgat 7740 ttgaaattaa aacttcaagc tgaatgactt atatgagaat aatacgttca atcaaagtag 7800 ttattctatt ttgtgtccat attccattag attgtgatta ttaattttct agctatggta 7860 ttactatatc acacttgtga gtatgtattc aaatactaag tatcttatat gctacgtgca 7920 tacacattct tttcttaaac tttacctgtg ttttaactaa tattgtgtca gtgtattaaa 7980 aattagcttt tacatatgat atctacaatg taataaattt agagagtaat tttgtgtatt 8040 cttatttact taacatttta cttttaatta tgtaaatttg gttagaaaat aataataaat 8100 ggttagtgct attgtgtaat ggtagcagtt acaaaqagcc tctgccttcc caaactaata 8160 tttatcacac atggtcatta aatgggaaaa aaatagacta aacaaatcac aaattgttca 8220 WO 2004/098515 PCT/US2004/013568 259 gttcttaaaa tgtaattatg tcacacacac aaaaaatcct tttcaatcct qagaaaatta 820 aaggcgtttt actcacatgg ctatttcaac attagttttt tttgtttgtt tctttttcat 8340 ggtattactg aaggtgtgta tactccctaa tacacattta tgaaaatcta cttgtttagg 8400 cttttattta tactcttctg atttatattt tttattataa ttattatttc ttatcttict 8460 tcttttatat tttttggaaa ccaaatttat agttagttta ggtaaacttt ttattatgac 8520 cattagaaac tattttgaat gcttccaact ggctcaattg gccgggaaaa catgggagca 8580 agagaagctg aaatatattt ctgcaagaac ctttctatat tatgtgccaa ttaccacacc 8640 agatcaattt tatgcagagg ccttaaaata ttctttcaca gtagctttct tacactaacc 8700 gtcatgtgct tttagtaaat atgattttta aaagcagttc aagttgacaa cagcagaaac 8760 agtaacaaaa aaatctgctc agaaaaatgt atgtgcacaa ataaaaaaaa ttaatqgcaa 8820 ttgtttagtg attgtaagtg atacttttta aagagtaaac tgtgtgaaat ttatactatc 8880 cctgcttaaa atattaagat ttttatgaaa tatgtattta tgtttgtatt gtgggaagat 8940 tcctcctctg tgatatcata cagcatctga aagtgaacag tatcccaaag cagttccaac 9000 catgctttgg aagtaagaag gttgactatt gtatggccaa ggatggcagt atgtaatcca 9060 gaagcaaact tgtattaatt gttctatttc aggttctgta ttgcatgttt tcttattaat 9120 atatattaat aaaagttatg agaaat 9146 Table 1.I11(c). Nucleotide sequence alignment of 109PI D4 v.1 (SEQ ID NO: 250) and 11091311D4 v.4 (SEQ ID NO: 251) Score 7456 bits (3878), Expect = O.0identities = 3878/3878 (100%) Strand = Plus I Plus V.1 1 ctggtggtccagtacctccaaagatatggaatacactctgaaattcctgaaaactttt 60 V.4 1 ctggtggtccagtacctccaaagatatggaatacactcctgaaatatcctgaaaactttt 60 V.1 61 ttttttcagaatcctttaataagcagttatgtcaatctgaaagttgcttacttgtacttt 120 V.4 61 ttttaatctatacgttgcacgagtctcttct 120 V.1 121 atattaatagctattcttgtttttcttatccaaagaaaaatcctctaatccccttttcac 180 V 121 ttctttccaag ctttc V.1 181 atgatagttgttaccatgtttaggcattagtcacatcaagccCtctCctctcccaaactt 240 VA4 181 atgatagttgttaccatgtttaggcattagtcacatcaacccctctcctccccaaactt 240 V.1 241 0ttgtgaat0 V.4 241 cttctaacactatgcctctaatatctctgtt 300 V.1 301 tccagatcaattttttttcactttgatgcccagagctgaagaaatggactactgtataaa 360 V.4 301 tccagatcaattttttttcactttgatgcccagagctgaagaaatggactactgtataaa 360 V.1 361 0tat caaag V.4 361 gg0taggca V.1 421 0ttgcattt V.4 421 2 480 V.1 481 tctttttta 40 V 481 cttttta 40 V.1 541 tataatggtggacacttttataggtactctgtgtcatttttgatactgtaggtatctta 600 1111111 IIIIIIIIIII II IIIIttattatgacIII II852011 WO 2004/098515 PCT/US2004/013568 260 V.4 : 541 tatcaatggtggacacttttataggtactctgtgtcatttttgatactgtaggtatctta 600 V.1 : 601 tttcatttatctttattcttaatgtacgaattcataatatttgattcagaacaaatttat 660 I i Ii IIiIlIIiliilIIlIiIllIlIiIIi I 1 11 I l I 1 1 11l I 1 1 I 11ll 1I 111II V.4 : 601 tttcatttatctttattcttaatgtacgaattcataatatttgattcagaacaaatttat 660 V.1 : 661 cactaattaacagagtgtcaattatgctaacatctcatttactgattttaatttaaaaca 720 | | 1 1 1 1 | | 1 1 11 1 |1 11 1 11 1 1 1 1 1 1 1 1 1l l l l l l l l l i l l l l l l l l l l l l l l ll V.4 : 661 cactaattaacagagtgtcaattatgctaacatctcatttactgattttaatttaaaaca 720 V.1 : 721 gtttttgttaacatgcatgtttagggttggttcttaataatttcttcttcctcttctct 700 I l l l l l I I l ll I 1ll ll l l 1ll l l l l l l l l l l || 1 1 1 11 1 1 1 l l l l l l l l l i V.4 : 721 gtttttgttaacatgcatgtttagggttggcttcttaataatttcttcttcctcttctct 780 V.1 : 781 ctctcctcttcttttggtcagtgttgtgcgggttaatacaacaaactgtaacaagtgtac 840 11i 11l1il l 1 ll|11111 |11 I 1111111111111111 11[ ll i 111111111,11 V.4 : 781 ctctcctcttcttttggtcagtgttgtgcgggttaatacaacaaactgtaacaagtgtac 840 V.1 : 841 ctggtatggacttgttgtccgggacgtacattttcgcggtcctgctagcatgcgtggtgt 900 l iii| 1 I | | ||l I ii ii l ii i l111 l 1I I | 11I 1 l I1 | 11 I 1 1I1 I1 II1 I i1 I V.4 : 841 ctggtatggacttgttgtccgggacgtacattttcgcggtcctgctagcatgcgtggtgt 900 V.1 : 901 tccactctggcgcccaggagaaaaactacaccatccgagaagaaatgccagaaaacgtcc 960 |1I I I iIIll liillI |li 1l11 1111 11 l l 1 1I 1|l 1 I |111 l Iiii 11l 111111I I I|I1 V.4 : 901 tccactctggcgcccaggagaaaaactacaccatccgagaagaaatgccagaaaacgtcc 960 V.1 961 tgataggcgacttgttgaaagaccttaacttgtcgctgattccaaacaagtccttgacaa 1020 11 11!iiiiI 1 1 1 i ii II I Il l i i III III i i I11 11 1 |111ll 1 I l I1 I i 1 V.4 961 tgataggcgacttgttgaaagaccttaacttgtcgctgattccaaacaagtccttgacaa 1020 V.1 1021 ctgctatgcagttcaagctagtgtacaagaccggagatgtgccactgattcgaattgaag 1080 V.4 1021 ctgctatgcagttcaagctagtgtacaagaccggagatgtgccactgattcgaattgaag 1080 V.1 1081 aggatactggtgagatcttcactactggcgctcgcattgatcgtgagaaattatgtgctg 1140 V.4 1081 aggatactggtgagatcttcactactggcgctcgcattgatcgtgagaaattatgtgctg 1140 V.1 1141 gtatcccaagggatgagcattgcttttatgaagtggaggttgccattttgccggatgaaa 1200 V.4 1141 gtatcccaagggatgagcattgcttttatgaagtggaggttgccattttgcggatgaaa 1200 V.1 1201 tatttagactggttaagatacgttttctgatagaagatataaatgataatgcaccattgt 1260 V.4 1201 tatttagactggttaagatacgttttctgatagaagatataaatgataatgcaccattgt 1260 V.1 1261 tcccagcaacagttatcaacatatcaattccagagaactcggctataaactctaaatata 1320 V.4 1261 tcccagcaacagttatcaacatatcaattccagagaactcggctataaactctaaatata 1320 V.1 1321 ctctcccagcggctgttgatcctgacgtaggaataaacggagttcaaaactacgaactaa 1380 V.4 1321 ctctcccagcggctgttgatcctgacgtaggaataaacggagttcaaaactacgaactaa 1380 V.1 1381 ttaagagtcaaaacatttttggcctcgatgtcattgaaacaccagaaggagacaagatgc 1440 WO 2004/098515 PCT/US2004/013568 261 I I l 11I 11111 I ll |I1 iI II 111 1111 1 IiI iiiI|1 i I i I i I i V.4 1381 ttaagagtcaaaacatttttggcctcgatgtcattgaaacaccagaaggagacaagatgc 1440 V.1 1441 cacaactgattgttcaaaaggagttagatagggaagagaaggatacctacgtgatgaaag 1500 ll i I i Il| |l I ii I I I lI 11 111i lI 11 1 11111111 ii ii I iI ii Ii 1 i 11I V.4 1441 cacaactgattgttcaaaaggagttagatagggaagagaaggatacctacgtgatgaaag 1500 V.1 1501 taaaggttgaagatggtggctttcctcaaagatccagtactgctattttgcaagtgagtg 1560 Ill il illl i i III 1l Il111111111111111 11111111111 i 1111111111 V.4 1501 taaaggttgaagatggtggctttcctcaaagatccagtactgctattttgcaagtgagtg 1560 V.1 1561 ttactgatacaaatgacaaccacccagtctttaaggagacagagattgaagtcagtatac 1620 V.4 1561 ttactgatacaaatgacaaccacccagtctttaaggagacagagattgaagtcagtatac 1620 V.1 1621 cagaaaatgctcctgtaggcacttcagtgacacagctccatgccacagatgctgacatag 1680 I Il Ii i i ii II iI i I| 1 |1 i I i IiIiiiii 1 I|1 1 II1 i Ii i i 1 i ii II V.4 1621 cagaaaatgctcctgtaggcacttcagtgacacagctccatgccacagatgctgacatag 1680 V.1 1681 gtgaaaatgccaagatccacttctctttcagcaatctagtctccaacattgccaggagat 1740 V.4 1681 gtgaaaatgccaagatccacttctctttcagcaatctagtctccaacattgccaggagat 1740 V.1 1741 tatttcacctcaatgccaccactggacttatcacaatcaaagaaccactggatagggaag 1800 V.4 1741 tatttcacctcaatgccaccactggacttatcacaatcaaagaaccactggatagggaag 1800 V.1 1801 aaacaccaaaccacaagttactggttttggcaagtgatggtggattgatgccagcaagag 1860 V.4 1801 aaacaccaaaccacaagttactggttttggcaagtgatggtggattgatgccagcaagag 1860 V.1 1861 caatggtgctggtaaatgttacagatgtcaatgataatgtcccatccattgacataagat 1920 V.4 1861 caatggtgctggtaaatgttacagatgtcaatgataatgtcccatccattgacataagat 1920 V.1 1921 acatcgtcaatcctgtcaatgacacagttgttctttcagaaaatattccactcaacacca 1980 V.4 1921 acatcgtcaatcctgtcaatgacacagttgttctttcagaaaatattccactcaacacca 1980 V.1 1981 aaattgctctcataactgtgacggataaggatgcggaccataatggcagggtgacatgct 2040 V.4 1981 aaattgctctcataactgtgacggataaggatgcggaccataatggcagggtgacatgct 2040 V.1 2041 tcacagatcatgaaatccctttcagattaaggccagtattcagtaatcagttcctcctgg 2100 I l i ||ll |11 1 Il I Il ll 1 I IlI 1l l il Il I I I| 1II 1 I Il l il111 V.4 2041 tcacagatcatgaaatccctttcagattaaggccagtattcagtaatcagttcctcctgg 2100 V.1 2101 agactgcagcatatcttgactatgagtccacaaaagaatatgccattaaattactggctg 2160 V.4 2101 agactgcagcatatcttgactatgagtccacaaaagaatatgccattaaattactggctg 2160 V.1 2161 cagatgctggcaaacctcctttgaatcagtcagcaatgctcttcatcaaagtgaaagatg 2220 V.4 2161 cagatgctggcaaacctcctttgaatcagtcagcaatgctcttcatcaaagtgaaagatg 2220 WO 2004/098515 PCT/US2004/013568 262 V.1 2221 aaaatgacaatgctccagttttcacccagtctttcgtaactgtttctattcctgagaata 2280 I l l l l l l l l I l l i l l l l I l l l l l l l l l I l l l l I l l l l l 1 l l l l l l1 i l1 i l I l l l1 V.4 2221 aaaatgacaatgctccagttttcacccagtctttcgtaactgtttctattcctgagaata 2280 V.1 2281 actctcctggcatccagttgacgaaagtaagtgcaatggatgcagacagtgggcctaatg 2340 l Il|Il Ili I 1 l11 |1Il1 1111 111111l IlI ll I I I 1 |1 Illl I V.4 2281 actctcctggcatccagttgacgaaagtaagtgcaatggatgcagacagtgggcctaatg 2340 V.1 2341 ctaagatcaattacctgctaggccctgatgctccacctgaattcagcctggattgtcgta 2400 1111I1 I | 1 IlllIIIIIlIIIII iillI II i 11I111 1I I I l11I I1I11 I111 11 i 1 I l ii i V.4 2341 ctaagatcaattacctgctaggccctgatgctccacctgaattcagcctggattgtcgta 2400 V.1 2401 caggcatgctgactgtagtgaagaaactagatagagaaaaagaggataaatatttattca 2460 111 11 Ill l I l I I I Il 1111 I liil I Ii l 11 1 I l i i Il I Il V.4 2401 caggcatgctgactgtagtgaagaaactagatagagaaaaagaggataaatatttattca 2460 V.1 2461 caattctggcaaaagataacggggtaccacccttaaccagcaatgtcacagtctttgtaa 2520 l l l l i I i i1l1l1 ll 111111111 jilil 11Il11 1l1Il 1|1 l I l Ill l V.4 2461 caattctggcaaaagataacggggtaccacccttaaccagcaatgtcacagtctttgtaa 2520 V.1 2521 gcattattgatcagaatgacaatagcccagttttcactcacaatgaatacaacttctatg 2580 I IlI Il 11I Il i lli Ili I l i i 1I1Il 11 lII l11 l i i 1 11111111I V.4 2521 gcattattgatcagaatgacaatagcccagttttcactcacaatgaatacaacttctatg 2580 V.1 2581 tcccagaaaaccttccaaggcatggtacagtaggactaatcactgtaactgatcctgatt 2640 l l i l l l i I I 1 1 1 I l l i l | I I l l l l l | I l l l l l l l ll i l l l i lI l l V.4 2581 tcccagaaaaccttccaaggcatggtacagtaggactaatcactgtaactgatcctgatt 2640 V.1 2641 atggagacaattctgcagttacgctctccattttagatgagaatgatgacttcaccattg 2700 11111111Illll11l illl Illll 111111ii1111l illllllll 111l IIl1Ill1Il V.4 2641 atggagacaattctgcagttacgctctccattttagatgagaatgatgacttcaccattg 2700 V.1 2701 attcacaaactggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatctt 2760 V.4 2701 attcacaaactggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatctt 2760 V.1 2761 acactttctatgtaaaggctgaggatggtggtagagtatcacgttcttcaagtgccaaag 2820 V.4 2761 acactttctatgtaaaggctgaggatggtggtagagtatcacgttcttcaagtgccaaag 2820 V.1 2821 taaccataaatgtggttgatgtcaatgacaacaaaccagttttcattgtccctccttcca 2880 ll l111 111111Ill 1111111111111 11111 Illlllll il illlllllll V.4 2821 taaccataaatgtggttgatgtcaatgacaacaaaccagttttcattgtccctccttcca 2880 V.1 2881 actgttcttatgaattggttctaccgtccactaatccaggcacagtggtctttcaggtaa 2940 V.4 2881 actgttcttatgaattggttctaccgtccactaatccaggcacagtggtctttcaggtaa 2940 V.1 2941 ttgctgttgacaatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaa 3000 V.4 2941 ttgctgttgacaatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaa 3000 V.1 3001 acacaagagatctgtttgcaatcgaccaagaaacaggcaacataacattgatggagaaat 3060 V A13001 111 III1 ilIIiII1 i i I I l l i i I|||IIl l II1 I 3 6 V.4 :3001 acacaagagatetgtttgcaategaccaagaaacaggcaacataacattgatggagaaat 3060 WO 2004/098515 PCT/US2004/013568 263 V.1 3061 gtgatgttacagaccttggtttacacagagtgttggtcaaagctaatgacttaggacagc 3120 11111111111I1 1111 11111 1111111111111111I11I II I 111I II II II II II I|1 l I1I11I1 V.4 3061 gtgatgttacagaccttggtttacacagagtgttggtcaaagctaatgacttaggacagc 3120 V.1 3121 ctgattctctcttcagtgttgtaattgtcaatctgttcgtgaatgagtcggtgaccaatg 3180 V.4 3121 ctgattctctcttcagtgttgtaattgtcaatctgttcgtgaatgagtcggtgaccaatg 3180 V.1 3181 ctacactgattaatgaactggtgcgcaaaagcactgaagcaccagtgaccccaaatactg 3240 lI ii 11i1111l11111111I1i I lI1I11 111I 11111111111l1111111111111I |I I ||| I I| V.4 3181 ctacactgattaatgaactggtgcgcaaaagcactgaagcaccagtgaccccaaatactg 3240 V.1 3241 agatagctgatgtatcctcaccaactagtgactatgtcaagatcctggttgcagctgttg 3300 11i1I11I11 I I lIlli I 1 11||l11 II 1| 1 | I||11 111111 V.4 3241 agatagctgatgtatcctcaccaactagtgactatgtcaagatcctggttgcagctgttg 3300 V.1 3301 ctggcaccataactgtcgttgtagttattttcatcactgctgtagtaagatgtcgccagg 3360 l I I 1 ii i I l I iI l i Il II I II 111l 1 11 1 1 11|111 1 1 111 I 11II| V.4 3301 ctggcaccataactgtcgttgtagttatttcatcactgctgtagtaagatgtcgccagg 3360 V.1 3361 caccacaccttaaggctgctcagaaaaacaagcagaattctgaatgggctaccccaaacc 3420 l I 11l1I 11111111111111I I I I I i l I IIil lIIIII 11| I II i ii | I i I I V.4 3361 caccacaccttaaggctgctcagaaaaacaagcagaattctgaatgggctaccccaaacc 3420 V.1 3421 cagaaaacaggcagatgataatgatgaagaaaaagaaaaagaagaagaagcattccccta 3480 Il I 111111l 111l 11l l 1i l 1 11111 Ii I I IIIIII|IlIIIIIIIIIIl III II 1111 11 1 1 11 1 1 1 I I V.4 3421 cagaaaacaggcagatgataatgatgaagaaaaagaaaaagaagaagaagcattccccta 3480 V.1 3481 agaacttgctgcttaattttgtcactattgaagaaactaaggcagatgatgttgacagtg 3540 l111l1 ll1 lIl lIIiilI III1 I I1 l1 I1 1 i1111 1 I1 I|111I I 1] I II 111|I I | V.4 3481 agaacttgctgcttaattttgtcactattgaagaaactaaggcagatgatgttgacagtg 3540 V.1 3541 atggaaacagagtcacactagaccttcctattgatctagaagagcaaacaatgggaaagt 3600 |111 I I|1i I l1111 I IIl II11I II1 I I111 11 |11 1 111I [1i 1 iI l 1 11I II1 V.4 3541 atggaaacagagtcacactagaccttcctattgatctagaagagcaaacaatgggaaagt 3600 V.1 3601 acaattgggtaactacacctactactttcaagcccgacagccctgatttggcccgacact 3660 l ii 1 I1 I li i i 1111111111I 11111|111 III Iii [1111I |I IIlI I| 1 11111 V.4 3601 acaattgggtaactacacctactactttcaagcccgacagccctgatttggcccgacact 3660 V.1 3661 acaaatctgcctctccacagcctgccttccaaattcagcctgaaactcccctgaattcga 3720 V.4 3661 acaaatctgcctctccacagcctgccttccaaattcagcctgaaactcccctgaattcga 3720 V.1 3721 agcaccacatcatccaagaactgcctctcgataacacctttgtggcctgtgactctatct 3780 1111 11111111111111111111 11111111111 1111l I I | I I I l 1I lI Il| I1 I1 I I I V.4 3721 agcaccacatcatccaagaactgcctctcgataacacctttgtggcctgtgactctatct 3780 V.1 3781 ccaagtgttcctcaagcagttcagatccctacagcgtttctgactgtggctatccagtga 3840 1 II |1I l IiiiI ii lI l|1I li1 1111 I 1111 I l I 111111 I III II 1 I I I V.4 3781 ccaagtgttcctcaagcagttcagatccctacagcgtttctgactgtggctatccagtga 3840 V.1 3841 cgaccttcgaggtacctgtgtccgtacacaccagaccg 3878 V.4 3841 cgaccttcgaggtacctgtgtccgtacacaccagaccg 3878 WO 2004/098515 PCT/US2004/013568 264 Table LIV(c). Peptide sequences of protein coded by 109P1 D4 v.4 (SEQ ID NO: 252) MDLLSGTYIF AVLLACVVFH SGAQEKNYTI REEMPENVLI GDLLKDLNLS LIPNKSLTTA 60 MQFKLVYKTG DVPLIRIEED TGEIFTTGAR IDREKLCAGI PRDEHCFYEV EVAILPDEIF 120 RLVKIRFLIE DINDNAPLFP ATVINISIPE NSAINSKYTL PAAVDPDVGI NGVQNYELIK 180 SQNIFGLDVI ETPEGDKMPQ LIVQKELDRE EKDTYVMKVK VEDGGFPQRS STAILQVSVT 240 DTNDNHPVFK ETEIEVSIPE NAPVGTSVTQ LHATDADIGE NAKIHFSFSN LVSNIARRLF 300 HLNATTGLIT IKEPLDREET PNHKLLVLAS DGGLMPARAM VLVNVTDVND NVPSIDIRYI 360 VNPVNDTVVL SENIPLNTKI ALITVTDKDA DHNGRVTCFT DHEIPFRLRP VFSNQFLLET 420 AAYLDYESTK EYAIKLLAAD AGKPPLNQSA MLFIKVKDEN DNAPVFTQSF VTVSIPENNS 480 PGIQLTKVSA MDADSGPNAK INYLLGPDAP PEFSLDCRTG MLTVVKKLDR EKEDKYLFTI 540 LAKDNGVPPL TSNVTVFVSI IDQNDNSPVF THNEYNFYVP ENLPRHGTVG LITVTDPDYG 600 DNSAVTLSIL DENDDFTIDS QTGVIRPNIS FDREKQESYT FYVKAEDGGR VSRSSSAKVT 660 INVVDVNDNK PVFIVPPSNC SYELVLPSTN PGTVVFQVIA VDNDTGMNAE VRYSIVGGNT 720 RDLFAIDQET GNITLMEKCD VTDLGLHRVL VKANDLGQPD SLFSVVIVNL FVNESVTNAT 780 LINELVRKST EAPVTPNTEI ADVSSPTSDY VKILVAAVAG TITVVVVIFI TAVVRCRQAP 840 HLKAAQKNKQ NSEWATPNPE NSQMIMMKKK KKKKKHSPKN LLLNFVTIEE TKADDVDSDG 900 NRVTLDLPID LEEQTMGKYN WVTTPTTFKP DSPDLARHYK SASPQPAFQI QPETPLNSKH 960 HIIQELPLDN TFVACDSISK CSSSSSDPYS VSDCGYPVTT FEVPVSVHTR PPMKEVVRSC 1020 TPMKESTTME IWIHPQPQSQ RRVTFHLPEG SQESSSDGGL GDHDAGSLTS TSHGLPLGYP 1080 QEEYFDRATP SNRTEGDGNS DPESTFIPGL KKAAEITVQP TVEEASDNCT QECLIYGHSD 1140 ACWMPASLDH SSSSQAQASA LCHSPPLSQA STQHHSPRVT QTIALCHSPP VTQTIALCHS 1200 PPPIQVSALH HSPPLVQATA LHHSPPSAQA SALCYSPPLA QAAAISHSSP LPQVIALHRS 1260 QAQSSVSLQQ GWVQGADGLC SVDQGVQGSA TSQFYTMSER LHPSDDSIKV IPLTTFTPRQ 1320 QARPSRGDSP IMEEHPL 1337 Table LV(c). Amino acid sequence alignment of 109PID4 v.1 (SEQ ID NO: 253) and 109P1D4 v.4 (SEQ ID NO: 254) Score 2005 bits (5195), Expect = 0,0 dentities = 1011/1011 (100%), Positives = 1011/1011 (100%) V.1 1 MDLLSGTYIFAVLLACVVFHSGAQEKNYTIREEMPENVLIGDLLKDLNLSLIPNKSLTTA 60 MDLLSGTYIF AVLLACVVFHSGAQEKNYTIREEMPENVLIGDLLKDLNLSLIPNKSLTTA V. 4 1 MDLLSGTYIFAVLLACVVFHSGAQEKNYTIREEMPENVLIGDLLKDLNLSLIPNKSLTTA 60 V.1 61 MQFKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIF 120 MQFKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIF V.4 61 MQFKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIF 120 V.1 121 RLVKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIK 180 RLVKIRFLIEDTNDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIK V.4 121 RLVKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIK 180 V.1 181 SQNIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVT 240 SQNIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVT V.4 181 SQNIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVT 240 V.1 241 DTNDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLF 300 DTNDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLF V.4 241 DTNDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLF 300 V.1 301 HLNATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYI 360 HLNATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYT V.4 301 HLNATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYI 360 V.1 361 VNPVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLET 420 VNPVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLET V.4 361 VNPVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLET 420 V.1 421 AAYLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNS 480 AAYLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNS V.4 421 AAYLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNS 480 V.1 481 PGIQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTVVKKLDREKEDKYLFTI 540

PGIQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTVVKKLDREKEDKYLFTI

WO 2004/098515 PCT/US2004/013568 265 V.4 481 PGIQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTVVKKLDREKEDKYLFTI 540 V.1 541 LAKDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYG 600 LAKDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYG V. 4 541 LAKDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYG 600 V.1 601 DNSAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVT 660 DNSAVTLSILDENDDFTIDSQTVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVT V.4 601 DNSAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVT 660 V.1 661 INVVDVNDNKPVFIVPPSNCSYELVLPSTNPGTVVFQVIAVDNDTGMNAEVRYSIVCGNT 720 INVVDVNDNKPVFIVPPSNCSYELVLPSTNPGTVVFQVIAVDNDTGMNAEVRYSIVGGNT V.4 661 INVVDVNDNKPVFIVPPSNCSYELVLPSTNPGTVVFQVIAVDNDTGM6NAEVRYSIVGGNT 720 V.1 721 RDLFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSVVIVNLFVNESVTNAT 780 RDLFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSVVIVNLFVNESVTNAT V.4 721 RDLFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSVVIVNLFVNESVTNAT 780 V.1 781 LINELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVVVVIFITAVVRCRQAP 840 LINELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVVVVIFITAVVRCRQAP V.4 781 LINELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVVVVIFITAVVRCRQAP 840 V.1 841 HLKAAQKNKQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDG 900 HLKAAQKNKQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDG V.4 841 HLKAAQKNKQNSEWATPNPENRQMIMMKKKKKKKHSPKNLLLNFVTIEETKADDVDSDG 900 V.1 901 NRVTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNSKH 960 NRVTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNSKH V.4 901 NRVTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNSKH 960 V.1 961 HIIQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP 1011 HIIQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP V.4 961 HIIQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP 1011 Table LII(d). Nucleotide sequence of transcript variant 109PID4 v.5 (SEQ ID NO: 255) ctggtggtcc agtacctcca aagatatgga atacactcct gaaatatcct gaaaactttt 60 ttttttcaga atcctttaat aagcagttat gtcaatctga aagttgctta cttgtacttt 120 atattaatag ctattcttgt ttttcttatc caaagaaaaa tcctctaatc cccttttcac 180 atgatagttg ttaccatgtt taggcattag tcacatcaac ccctctcctc tcccaaactt 240 ctcttcttca aatcaaactt tattagtccc tcctttataa tgattccttg cctcgtttta 300 tccagatcaa ttttttttca ctttgatgcc cagagctgaa gaaatggact actgtataaa 360 ttattcattg ccaagagaat aattgcattt taaacccata ttataacaaa gaataatgat 420 tatattttgt gatttgtaac aaataccctt tattttccct taactattga attaaatatt 480 ttaattattt gtattctctt taactatctt ggtatattaa agtattatct tttatatatt 540 tatcaatggt ggacactttt ataggtactc tgtgtcattt ttgatactgt aggtarctta 600 tttcatttat ctttattctt aatgtacgaa ttcataatat ttgattcaga acaaatttat 660 cactaattaa cagagtgtca attatgctaa catctcattt actgatttta atttaaaaca 720 gtttttgtta acatgcatgt ttagggttgg cttcttaata atttcttctt cctcttctct 780 ctctcctctt cttttggtca gtgttgtgcg ggttaataca acaaactqta acaagtgtac 840 ctggtatgga cttgttgtcc gggacgtaca ttttcgcggt cctgctagca tgcgtggtgt 900 tccactctgg cgcccaggag aaaaactaca ccatccgaga agaaatgcca gaaaacgtcc 960 tgataggcga cttgttgaaa gaccttaact tgtcgctgat tccaaacaag tccttgacaa 1020 ctgctatgca gttcaagcta gtgtacaaga ccggagatgt gccactgatt cgaattgaag 1080 aggatactgg tgagatcttc actactggcg ctcgcattga tcgtgagaaa ttatgtgctg 1140 gtatcccaag ggatgagcat tgcttttatg aagtggaggt tgccattttg ccggatgaaa 1200 tatttagact ggttaagata cgttttctga tagaagatat aaatgataat gcaccattgt 1260 tcccagcaac agttatcaac atatcaattc cagagaactc ggctataaac tctaaatata 1320 ctctcccagc ggctgttgat cctgacgtag gaataaacgg agttcaaaac tacgaactaa 1380 ttaagagtca aaacattttt ggcctcgatg tcattgaaac accagaagga gacaagatgc 1440 cacaactgat tgttcaaaag gagttagata gggaagagaa ggatacctac gtgatgaaag 1500 taaaggttga agatggtggc tttcctcaaa gatccagtac tgctattttg caagtgagtg 1560 ttactgatac aaatgacaac cacccagtct ttaaggagac agagattgaa gtcagtatac 1620 cagaaaatgc tcctgtaggc acttcagtga cacagctcca tgccacagat gctgacatag 1680 gtgaaaatgc caagatccac ttctctttca gcaatctagt ctccaacatt gccaggagat 1740 tatttcacct caatgccacc actggactta tcacaatcaa agaaccactg gatagggaag 1800 WO 2004/098515 PCT/US2004/013568 266 aaacaccaaa ccacaagtta ctggttttgg caagtgatgg tggattgatg ccagcaagag 1860 caatggtgct ggtaaatgtt acagatgtca atgataatgt cccatccatt gacataagat 1920 acatcgtcaa tcctgtcaat gacacagttg ttctttcaga aaatattcca ctcaacacca 1980 aaattgctct cataactgtg acggataagg atgcggacca taatggcagg gtgacatgct 2040 tcacagatca tgaaatccct ttcagattaa ggccagtatt cagtaatcag ttcctcctgg 2100 agactgcagc atatcttgac tatgagtcca caaaagaata tgccattaaa ttactggctg 2160 cagatgctg caaacctcct ttgaatcagt cagcaatgct cttcatcaaa tgaaagatg 2220 aaaatgacaa tgctccaqtt ttcacccagt ctttcgtaac tgtttctatt cctgagaata 2280 actctcctgg catccagttg acqaaagtaa gtqcaatgga tgcagacagt gggcctaatg 2340 ctaagatcaa ttacctgcta ggccctgatg ctccacctga attcagcctg gattgtcgta 2400 caggcatgct gactgtagtg aagaaactag atagagaaaa agaggataaa tatttattca 2460 caattctggc aaaagataac gggctaccac ccttaaccag caatgtcaca gtotttgtaa 2520 gcattattga tcagaatgac aatagcccag ttttcactca caatgaatac aacttctatg 2580 tcccagaaaa ccttccaagg catggtacag taqgactaat cactgtaact qatcctgatt 2640 atggagacaa ttctgcagtt acgctctcca ttttagatga gaatgatgac ttcaccattg 2700 attcacaaac tggtgtcatc cgaccaaata tttcatttga tagagaaaaa caagaatctt 2760 acactttcta tgtaaaggct gaggatggtg gtagagtatc acgttcttca agtgccaaag 2820 taaccataaa tgtggttgat gtcaatgaca acaaaccagt tttcattgtc cctccttcca 2880 actgttctta tgaattggtt ctaccgtcca ctaatccagg cacagtggtc tttcaggtaa 2940 ttgctgttga caatgacact ggcatgaatg cagaggttcg ttacagcatt gtaggaggaa 3000 acacaagaga tctgtttgca atcqaccaag aaacaggcaa cataacattg atggagaaat 3060 gtgatgttac agaccttggt ttacacagag tgttggtcaa agctaatgac ttaggacagc 3120 ctgattctct cttcagtgtt gtaattgtca atctgttcgt gaatgagtcg gtgaccaatg 3180 ctacactgat taatgaactg gtgcgcaaaa gcactgaagc accagtgacc ccaaatactg 3240 agatagctga tgtatcctca ccaactagtg actatgtcaa gatcctqgtt gcagctgttg 3300 ctggcaccat aactgtcgtt gtagttattt tcatcactgc tgtagtaaga tgtcgccagg 3360 caccacacct taaggctgct cagaaaaaca agcagaattc tgaatgqgct accccaaacc 3420 cagaaaacag gcagatqata atgatgaaga aaaagaaaaa gaagaagaag cattccccta 3480 agaacttgct gcttaatttt gtcactattg aagaaactaa ggcagatgat gttgacagtg 3540 atggaaacag agtcacacta gaccttccta ttgatctaga agagcaaaca atgggaaagt 3600 acaattgggt aactacacct actactttca agcccgacag ccctgatttg gcccgacact 3660 acaaatctgc ctctccacag cctgccttcc aaattcaccc tgaaactccc ctgaattcga 3720 agcaccacat catccaagaa ctgcctctcg ataacacctt tgtcgcctgt gactctatct 3780 ccaagtgttc ctcaagcagt tcagatccct acagcgtttc tgactgtggc tatccagtga 3840 cgaccttcga qgtacctgtg tccgtacaca ccagaccgtc ccagcggcgt gtcacatttc 3900 acctgtcaga aggctctcag gaaagcagca gtgatggtgg actgggagac catgatgcag 3960 gcagccttac catcacatct catgcctgc cccttggcta tcctcaggag gagtactttg 4020 atcgtgctac acccagcaat cgcactgaag gggatggcaa ctccgatcct gaatctactt 4080 tcatacctgg actaaagaaa gctgcagaaa taactgttca accaactgtg gaagaggcct 4140 ctgacaactg cactcaagaa tgtctcatc atggccattc tgatgcctgc tggatgccgg 4200 catctctgga tcattccagc tcttcgcaag caaaggcctc tgctctatgc cacagcccac 4260 cactgtcaca ggcctctact cagcaccaca gcccacgagt gacacagacc attgctctct 4320 gccacagccc tccagtgaca cagaccatcg cattqtgcca cagoccacca ccgatacagg 4380 tgtctgctct ccaccacagt cctcctctag tgcaggctac tgcacttcac cacagcccac 4440 catcagcaca ggcctcagcc ctctgctaca gccctccttt agcacaggct gctgcaatca 4500 gccacagctc tcctctgcca caggttattg ccctccatcg tagtcaggcc caatcatcag 4560 tcagtttgca gcaagttgg gtgcaaggtg ctgatgggct atgctctgtt gatcaggag 4620 tgcaaggtag tqcaacatct cagttttaca ccatgtctga aagacttcat cccagtgatg 4680 attcaattaa agtcattcct ttgacaacct tcactccacg ccaacaggcc agaccgtcca 4740 gaggtgattc ccccattatg gaagaacatc ccttgtaaag ctaaaatagt tacttcaaat 4800 tttcagaaaa gatgtatata gtcaaaattt aagatacaat tccaatgagt attctgatta 4860 tcagatttgt aaataactat gtaaatagaa acagatacca gaataaatct acactagac 4920 ccttagtcaa tcagttaacca aaaaattgca atttgtttaa ttcagaatgt gtatttaaaa 4980 agaaaaggaa tttaacaatt tgcatcccct tgtacagtaa ggcttatcat gacagagcgc 5040 actatttctc atgtacagta ttttttgttg tttttatcat catgtgcaat attactgatt 5100 tgtttccatg ctgattgtgt ggaaccagta tgtagcaaat ggaaagccta gaaatatctt 5160 attttctaag tttaccttta gtttacctaa acttttgttc agataacgtt aaaaggtata 5220 cgtactctag cctttttttg ggctttcttt ttgatttttj tttgttgttt tcagtttttt 5280 tgttgttgtt agtgagtctc ccttcaaaat acgcagtagg tagtgtaaat actgcttgtt 5340 tgtgtctctc tgctgtcatg ttttctacct tattccaata ctatattqtt qataaaattt 5400 gtatatacat tttcaataaa gaatatgtat aaactgtaca gatctagatc tacaacctat 5460 ttctctactc tttagtagag ttcgagacac agaagtgcaa taactgccct aattaagcaa 5520 WO 2004/098515 PCT/US2004/013568 267 ctatttgtta aaaagggcct ctttttactt taatagttta gtgtaaagta catcagaaat 5580 aaagctgtat ctgccatttt aagcctgtag tccattatta cttgggtctt tacttctggg 5640 aatttgtatg taacagccta gaaaattaaa aggaggtgga tgcatccaaa gcacgagtca 5700 cttaaaatat cgacggtaaa ctactatttt gtagagaaac tcaggaagat ttaaatgttg 5760 atttgacagc tcaataggct gttaccaaag ggtgttcagt aaaaataaca aatacatgta 5820 actgtagata aaaccatata ctaaatctat aagactaagg gatttttgtt attctagctc 5880 aacttactga agaaaaccac taataacaac aagaatatca ggaaggaact tttcaagaaa 5940 tgtaattata aatctacatc aaacacaatt ttaaggaaaa atgcagaggg agaaataagg 6000 cacatgactg cttcttgcag tcaacaagaa ataccaataa cacacacaga acaaaaacca 6060 tcaaaatctc atatatgaaa taaaatatat tcttctaagc aaagaaacag tactattcat 6120 agaaaacatt agttttcttc tgttgtctgt tatttccttc ttgtatcctc ttaactggcc 6180 attatcttgt atgtgcacat tttataaatq tacagaaaca tcaccaactt aattttcttc 6240 catagcaaaa ctgagaaaat accttgtttc agtataacac taaaccaaga gacaattgat 6300 gtttaatggg ggcggttggg gtgggggggg gagtcaatat ctcctattga ttaacttaga 6360 catagatttt gtaatgtata acttgatatt taatttatga ttaaactgtg tgtaaatttt 6420 gtaacataaa ctgtggtaat tgcataattt cattggtgag gatttccact gaatattgag 6480 aaagtttctt ttcatgtgcc cagcaggtta agtagcgttt tcagaatata cattattccc 6540 atccattgta aagttcctta agtcatattt gactgggcgt gcagaataac ttcttaactt 6600 ttaactatca gagtttgatt aataaaatta attaatgttt tttctccttc gtgttgttaa 6660 tgttccaagg gatttggagc atactggttt tccaggtgca tgtgaatccc gaaggactga 6720 tgatatttga atgtttatta aattattatc atacaaatgt gttgatattg tggctattgt 6780 tgatgttgaa aattttaaac ttggggaaga ttaagaaaag aaccaatagt gacaaaaatc 6840 agtgcttcca gtagatttta gaacattctt tgcctcaaaa aacctgcaaa gatgatgtga 6900 gattttttct tgtgttttaa tatta ttccctcaat attcg 66 atgatctaca cacacacaca cacacacacg tgcacacaca cacacattta aatgatataa 7020 aaagaagagg ttgaaagatt attaaataac ttatcaggca tctcaatggt tactatctat 7080 gttagtgaaa atcaaatagg actcaaagtt ggatatttgg gatttttctt ctgacagtat 7140 aatttattga gttactaggg aggttcttaa atcctcataL ctggaaactt gtgacgtttt 7200 gacacctttc ctatagatga tataggaatg aaccaatacg cttttattac cctttctaac 7260 tctgatttta taatcagact tagattgtgt ttagaatatt aaatgactgg gcaccctctt 7320 cttggttttt accagagagg ctttgaatgq aagcaggctg agagtagcca aagaggcaag 7380 gggtattagc ccagttattc tcccctatgc cttccttctc tttctaagcg tccactaggt 7440 ctggccttgg aaacctgtta cttctagggc ttcagatctg atgatatctt tttcatcaca 7500 ttacaagtta tttctctgac tgaatagaca gtggtatagg ttgacacagc acacaagtgg 7560 ctattgtgat gtatgatgta tgtagtccta caactgcaaa acgtcttact gaaccaacaa 7620 tcaaaaaatg gttctgtttt aaaaaggatt ttgttgatt tgaaattaaa acttcaagct 7680 gaatgactta tatgagaata atacgttcaa tcaaagtagt tattctattt tgtgtccata 7740 ttccattaga ttgtgattat taattttcta gctatggtat tactatatca cacttgtgag 7800 tatgtattca aatactaagt atcttatatg ctacgtgcat acacattctt ttcttaaact 7860 ttacctgtgt tttaactaat attgtgtcag tgtattaaaa attagctttt acatatgata 7920 tctacaatgt aataaattta gagagtaatt ttgtgtattc ttatttactt aacattttac 7980 ttttaattat gtaaatttgg ttagaaaata ataataaatg gttagtgcta ttgtgtaatg 8040 gtagcagtta caaagagcct ctgccttccc aaactaatat ttatcacaca tggtcattaa 8100 atgggaaaaa aatagactaa acaaatcaca aattgttcag ttcttaaaat gtaattatgt 8160 cacacacaca aaaaatcctt ttcaatcctg agaaaattaa aggcgtttta ctcacatggc 8220 tatttcaaca ttagtttttt ttgtttgttt ctttttcatg gtattactga aggtgtgtat 8280 actccctaat acacatttat gaaaatctac ttgtttaggc ttttatttat actcttctga 8340 tttatatttt ttattataat tattatttct tatctttctt cttttatatt ttttggaaac 8400 caaatttata gttagtttag gtaaactttt tattatgacc attaqaaact attttgaatg 8460 cttccaactg gctcaattgg ccgggaaaac atgggagcaa gagaagctga aatatatttc 8520 tgcaagaacc tttctatatt atgtgccaat taccacacca gatcaatttt atgcagaggc 8580 cttaaaatat tctttcacag tagctttctt acactaaccg tcatgtgctt ttagtaaata 8640 tgatttttaa aagcagttca agttgacaac agcagaaaca gtaacaaaaa aatctgctca 8700 gaaaaatgta tgtgcacaaa taaaaaaaat taatggcaat tgtttagtga ttgtaagtga 8760 tactttttaa agagtaaact gtgtgaaatt tatactatcc ctgcttaaaa tattaagatt 8820 tttatgaaat atgtatttat gtttqtattg tggqaagatt cctcctctgt gatatcatac 8880 agcatctgaa agtgaacagt atcccaaagc agttccaacc atgctttgga agtaagaagg 8940 ttgactattg tatggccaag gatggcagta tgtaatccag aagcaaactt gtattaattg 9000 ttctatttca ggttctgtat tgcatgtttt cttattaata tatattaata aaagttatga 9060 gaaat 9065 WO 2004/098515 PCT/US2004/013568 268 Table Llll(d). Nucleotide sequence alignment of 109PID4 v (SEQ ID NO: 256) and 109P1D4 v.5 (SEQ ID NO: 257) Score = 7456 bits (3878), Expect = 0.01dentities = 3878/3878 (100%) Strand = Plus / Plus V.1 1 ctggtggtccagtacctccaaagatatggaatacactcctgaaatatcctgaaaactttt 60 | |11 1 l l l l I l l l l li l l I ll l ll i l I II l l 1 1 1 1 1| | I I1 l l l l l l l l l l1 V.5 1 ctggtggtccagtacctccaaagatatggaatacactcctgaaatatcctgaaaactttt 60 V.1 61 ttttttcagaatcctttaataagcagttatgtcaatctgaaagttgcttacttgtacttt 120 I lIl 1 l III111 I l IlI I 11 1 1 11 1 1 11 1 1 1 I I Il I I IIl11I 1 II 1 ll I Il V.5 61 ttttttcagaatcctttaataagcagttatgtcaatctgaaagttgcttacttgtacttt 120 V.1 121 atattaatagctattcttgtttttcttatccaaagaaaaatcctctaatccccttttcac 180 1 1 1 1 1 I l l l l i I l l i l 1 1 1 1 1 1 1 1 1 1 1 1 1I l l l I l 11111 1ii 111111| |] V.5 121 atattaatagctattcttgtttttcttatccaaagaaaaatcctctaatccccttttcac 180 V.1 181 atgatagttgttaccatgtttaggcattagtcacatcaacccctctcctctcccaaactt 240 l1111111111111 1Il 1I1II1ll I l1 illllll11lll Il111 Il-l11111111 I V.5 181 atgatagttgttaccatgtttaggcattagtcacatcaacccctctcctctcccaaactt 240 V.1 241 ctcttcttcaaatcaaactttattagtccctcctttataatgattccttgcctcgtttta 300 l i l i l l l l l l l l l l l i l ll l l l l l l l l l l l l l l l l l l l l l l l l l l i l l ll l l l l V.5 241 ctcttcttcaaatcaaactttattagtccctcctttataatgattccttgcctcgtttta 300 V.1 301 tccagatcaattttttttcactttgatgcccagagctgaagaaatggactactgtataaa 360 V.5 301 tccagatcaattttttttcactttgatgcccagagctgaagaaatggactactgtataaa 360 V.1 361 ttattcattgccaagagaataattgcattttaaacccatattataacaaagaataatgat 420 l il llll llll lll llll llil ill 111 |111 11111 111 111||111111li 1 V.5 361 ttattcattgccaagagaataattgcattttaaacccatattataacaaagaataatgat 420 V.1 421 tatattttgtgatttgtaacaaataccctttattttcccttaactattgaattaaatatt 480 ||I|1111111111111111111111111111lllllilllllllllllll1llllill V.5 421 tatattttgtgatttgtaacaaataccctttattttcccttaactattgaattaaatatt 480 V. : 481 ttaattatttgtattctctttaactatcttggtatattaaagtattatcttttatatatt 540 11111111111111111] 1111111111||1lllI11lllllllllllilllllllllll V.5 481 ttaattatttgtattctctttaactatcttggtatattaaagtattatcttttatatatt 540 V.1 541 tatcaatggtggacacttttataggtactctgtgtcatttttgatactgtaggtatctta 600 V.5 541 tatcaatggtggacacttttataggtactctgtgtcatttttgatactgtaggtatctta 600 V.1 601 tttcatttatctttattcttaatgtacgaattcataatatttgattcagaacaaatttat 660 l i l l l l l l l l l l l I I ~ l l l l l l l I I~ l l l l l ll l l l l l l l l l l l l l l l l l l V.5 601 tttcatttatctttattcttaatgtacgaattcataatatttgattcagaacaaatttat 660 V.1 661 cactaattaacagagtgtcaattatgctaacatctcatttactgattttaatttaaaaca 720 V.5 661 cactaattaacagagtgtcaattatgctaacatctcatttactgattttaatttaaaaca 720 V.1 721 gtttttgttaacatgcatgtttagggttggcttcttaataatttcttcttcctcttctct 780 V.5 721 gtttttgttaacatgcatgtttagggttggttcttaataatttcttcttcctcttctct 780 V.1 781 ctctcctcttcttttggtcagtgttgtgcgggttaatacaacaaactgtaacaagtgtac 840 WO 2004/098515 PCT/US2004/013568 269 ilii | 1 | I 1 | 111111 1 II 1 i 111 1 II 1111I II 1 1 I I 111|||11 V.5 781 ctctcctcttcttttggtcagtgttgtgcgggttaatacaacaaactgtaacaagtgtac 840 V.1 841 ctggtatggacttgttgtccgggacgtacattttcgcggtcctgctagcatgcgtggtgt 900 11FF 11 |11111 111111lIII 11111111111lll illlllll1 llllllllllli I V.5 841 ctggtatggacttgttgtccgggacgtacattttcgcggtcctgctagcatgcgtggtgt 900 V.1 901 tccactctggcgcccaggagaaaaactacaccatccgagaagaaatgccagaaaacgtcc 960 V.5 901 tccactctggcgcccaggagaaaaactacaccatccgagaagaaatgccagaaaacgtcc 960 V.1 961 tgataggcgacttgttgaaagaccttaacttgtcgctgattccaaacaagtccttgacaa 1020 1 1 1 11 11FF 1Il l ll ll ll i |I Ill F i 11FF 111 1 1F111FF 11||Il ll FI Fl V.5 961 tgataggcgacttgttgaaagaccttaacttgtcgctgattccaaacaagtccttgacaa 1020 V.1 1021 ctgctatgcagttcaagctagtgtacaagaccggagatgtgccactgattgaattgaag 1080 V.5 1021 ctgctatgcagttcaagctagtgtacaagaccggagatgtgccactgattcgaattgaag 1080 V.1 1081 aggatactggtgagatcttcactactggcgctcgcattgatcgtgagaaattatgtgctg 1140 ilF1l111111l I llillF 1111 11F 111 FF il 1Il l i Fi il I IllI FI Il F i ll1 11l V.5 1081 aggatactggtgagatcttcactactggcgctcgcattgatcgtgagaaattatgtgctg 1140 V.1 1141 gtatcccaagggatgagcattgcttttatgaagtggaggttgccattttgccggatgaaa 1200 111||1Fl Il1111111IllFI 1 i 1 il 1 FF111111l Il1ll 1 ilFI 111l1111111l Il ll V.5 1141 gtatcccaagggatgagcattgcttttatgaagtggaggttgccattttgccggatgaaa 1200 V.1 1201 tatttagactggttaagatacgttttctgatagaagatataaatgataatgcaccattgt 1260 111il11iFillF 1 ||1l FF11111ll Il 1111F 1I||1FF 1 11111 ll 11FF III lFlF V.5 1201 tatttagactggttaagatacgttttctgatagaagatataaatgataatgcaccattgt 1260 V.1 1261 tcccagcaacagttatcaacatatcaattccagagaactcggctataaactctaaatata 1320 Il1i I11 il Il F lF 1I11 | F i l ll1 i 1 l1 ll I1 i iFF I I 111F I 1lI 11 Ilil V.5 1261 tcccagcaacagttatcaacatatcaattccagagaactcggctataaactctaaatata 1320 V.1 1321 ctctcccagcggctgttgatcctgacgtaggaataaacggagttcaaaactacgaactaa 1380 I Il1 FF1111~ I 11 1FFIIi 11111 I 11|1 1 lIiI | |1F 1 11F I III llIl V.5 1321 ctctcccagcggctgttgatcctgacgtaggaataaacggagttcaaaactacgaactaa 1380 V.1 1381 ttaagagtcaaaacatttttggcctcgatgtcattgaaacaccagaaggagacaagatgc 1440 Il il I II i I FF11111Il i l ll l111 11FF IlIIlII 11111F F|11 I Il i V.5 1381 ttaagagtcaaaacatttttggcctcgatgtcattgaaacaccagaaggagacaagatgc 1440 V.1 1441 cacaactgattgttcaaaaggagttagatagggaagagaaggatacctacgtgatgaaag 1500 Ill1F iIl 1| l FFI11||11 FFll 1 111 11 111 l l lIIi I|11F 11 V.5 1441 cacaactgattgttcaaaaggagttagatagggaagagaaggatacctacgtgatgaaag 1500 V.1 1501 taaaggttgaagatggtggctttcctcaaagatccagtactgctattttgcaagtgagtg 1560 11 FF111111I11I111I1Il 1111111111111111111 I I Fl 1111I1111 FF1111111|I I| V.5 1501 taaaggttgaagatggtggctttcctcaaagatccagtactgctattttgcaagtgagtg 1560 V.1 1561 ttactgatacaaatgacaaccacccagtctttaaggagacagagattgaagtcagtatac 1620 V.3 156 il 111I FF 111 FF1111 l 111 FF Il 111111 ililI I II I|lF 62 V.5 :1561 ttactgatacaaatgacaaccacccagtctttaaggagacagagattgaagtcagtatac 1620 WO 2004/098515 PCT/US2004/013568 270 V.1 1621 cagaaaatgctcctgtaggcacttcagtgacacagctccatgccacagatgctgacatag 1680 V.5 1621 cagaaaatgctcctgtaggcacttcagtgacacagctccatgccacagatgctgacatag 1680 V.1 1681 gtgaaaatgccaagatccacttctctttcagcaatctagtctccaacattgccaggagat 1740 I I i illIIIIIIlllIIIIIlIIIIIIIIIIIIIIIilI IIIIII 11 1 1 11I1 | 1 1 11 1 1 11 1 1 1 111111 i II1I1 V.5 1681 gtgaaaatgccaagatccacttctctttcagcaatctagttccaacattgccaggagat 1740 V.1 1741 tatttcacctcaatgccaccactggacttatcacaatcaaagaaccactggatagggaag 1800 l lI II Il I |1I II I1 I II II II1 1 I I | 1I I I l i|111 1 li V.5 1741 tatttcacctcaatgccaccactggacttatcacaatcaaagaaccactggatagggaag 1800 V.1 1801 aaacaccaaaccacaagttactggttttggcaagtgatggtggattgatgccagcaagag 1860 lI l l 111 111111111 II I I i I 1I I I I I11 I111I11I II Il1I111 I I 111I 1I1I V.5 1801 aaacaccaaaccacaagttactggttttggcaagtgatggtggattgatgccagcaagag 1860 V.1 1861 caatggtgctggtaaatgttacagatgtcaatgataatgtcccatccattgacataagat 1920 V.5 1861 caatggtgctggtaaatgttacagatgtcaatgataatgtcccatccattgacataagat 1920 V.1 1921 acatcgtcaatcctgtcaatgacacagttgttctttcagaaaatattccactcaacacca 1980 I iI l I I 11 11 I I1 I IlIlII I I II1 I1 I I 1l1 1 111111 III I1 1 1|11 I| V.5 1921 acatcgtcaatcctgtcaatgacacagttgttctttcagaaaatattccactcaacacca 1980 V.1 1981 aaattgctctcataactgtgacggataaggatgcggaccataatggcagggtgacatgct 2040 i lIiiI lII I l Il II I1 IilI| ||I I |1 1 1 I i I I 1 11 I Ii 1 II1 V.5 1981 aaattgctctcataactgtgacggataaggatgcggaccataatggcagggtgacatgct 2040 V.1 2041 tcacagatcatgaaatccctttcagattaaggccagtattcagtaatcagttctcctgg 2100 I 11l1111111I11I1111111Il I 111I11|1l Iiil1 ilI 1I | |1 iIi |111 II I I | I 1i V.5 2041 tcacagatcatgaaatccctttcagattaaggccagtattcagtaatcagttcctcctgg 2100 V.1 2101 agactgcagcatatcttgactatgagtccacaaaagaatatgccattaaattactggctg 2160 V.5 2101 agactgcagcatatcttgactatgagtccacaaaagaatatgccattaaattactggctg 2160 V.1 2161 cagatgctggcaaacctcctttgaatcagtcagcaatgctcttcatcaaagtgaaagatg 2220 ilI I i illiiIIIIII l1 II 111 11 1 1 1 11Ii 111111111| II II 1l I 11I || I I11I V.5 2161 cagatgctggcaaacctcctttgaatcagtcagcaatgctcttcatcaaagtgaaagatg 2220 V.1 2221 aaaatgacaatgctccagttttcacccagtctttcgtaactgtttctattcctgagaata 2280 V.5 2221 aaaatgacaatgctccagttttcacccagtctttcgtaactgtttctattcctgagaata 2280 V.1 2281 actctcctggcatccagttgacgaaagtaagtgcaatggatgcagacagtgggcctaatg 2340 l I 111l1I l i ii 1111111I 1|11Il II1I1 II11I1 I I 111 |II|1 I I1111 I 11 I|111II1I1 V.5 2281 actctcctggcatccagttgacgaaagtaagtgcaatggatgcagacagtgggcctaatg 2340 V.1 2341 ctaagatcaattacctgctaggccctgatgctccacctgaattcagcctggattgtcgta 2400 l 1111 i 111 iII |I iI |1 I11 1 111I1l1 I1 I | I I | | |II 111111 I I 1 I Ii I V.5 2341 ctaagatcaattacctgctaggccctgatgctccacctgaattcagcctggattgtcgta 2400 V.1 2401 caggcatgctgactgtagtgaagaaactagatagagaaaaagaggataaatatttattca 2460 V.5 2401 caggcatgctgactgtagtgaagaaactagatagagaaaaagaggataaatatttattca 2460 WO 2004/098515 PCT/US2004/013568 271 V.1 2461 caattctggcaaaagataacggggtaccacccttaaccagcaatgtcacagtctttgtaa 2520 I |Il|1 I 111 1 illlllIl ll|I I l l il Il ilI I I I Il 11 l 1I l 1I II V.5 2461 caattctggcaaaagataacggggtaccacccttaaccagcaatgtcacagtctttgtaa 2520 V.1 2521 gcattattgatcagaatgacaatagcccagttttcactcacaatgaatacaacttctatg 2580 i i|I Il i I lIii lIIli lII i i 1 1 1 1 1 1 1 1 1 11 IIiI l 1I II 11 11 11 1 Il V.5 2521 gcattattgatcagaatgacaatagcccagttttcactcacaatgaatacaacttctatg 2580 V.1 2581 tcccagaaaaccttccaaggcatggtacagtaggactaatcactgtaactgatcctgatt 2640 V.5 2581 tcccagaaaaccttccaaggcatggtacagtaggactaatcactgtaactgatcctgatt 2640 V.1 2641 atggagacaattctgcagttacgctctccattttagatgagaatgatgacttcaccattg 2700 V.5 2641 atggagacaattctgcagttacgctctccattttagatgagaatgatgacttcaccattg 2700 V.1 2701 attcacaaactggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatctt 2760 I I 11 I|1 I|11111 Il ll l |1 I I l i I i ii 11 1 1 |1 I 1i I 1 || 1 Iiiii1 l | V.5 2701 attcacaaactggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatctt 2760 V.1 2761 acactttctatgtaaaggctgaggatggtggtagagtatcacgttcttcaagtgccaaag 2820 V.5 2761 acactttctatgtaaaggctgaggatggtggtagagtatcacgttcttcaagtgccaaag 2820 V.1 2821 taaccataaatgtggttgatgtcaatgacaacaaaccagttttcattgtccctccttcca 2880 l Il 111I lI I 11 I 1 I 1111 l 1 l l |I iiI |1111 1 lI 1 l 1 l 1 |1111I111 V.5 2821 taaccataaatgtggttgatgtcaatgacaacaaaccagttttcattgtccctccttcca 2880 V.1 2881 actgttcttatgaattggttctaccgtccactaatccaggcacagtggtctttcaggtaa 2940 I I1111 1 i Ii i 11| Ii 11 i II i I Il I i il i I 1II l 1 11111I 11iI ll li ii iI 1lI I il V.5 2881 actgttcttatgaattggttctaccgtccactaatccaggcacagtggtctttcaggtaa 2940 V.1 2941 ttgctgttgacaatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaa 3000 V.5 2941 ttgctgttgacaatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaa 3000 V.1 3001 acacaagagatctgtttgcaatcgaccaagaaacaggcaacataacattgatggagaaat 3060 i I l I1I 111111111111 I 1I I i IIIIII 1 1 I i I lli I 1l i i 1 [II 11 11i V.5 3001 acacaagagatctgtttgcaatcgaccaagaaacaggcaacataacattgatggagaaat 3060 V.1 3061 gtgatgttacagaccttggtttacacagagtgttggtcaaagctaatgacttaggacagc 3120 l IiI III II il i I 1111111111111I 11i Ii i 1i I 1 l ii i i i 1 1 i 1I i I1 V.5 3061 gtgatgttacagaccttggtttacacagagtgttggtcaaagctaatgacttaggacagc 3120 V.1 3121 ctgattctctcttcagtgttgtaattgtcaatctgttcgtgaatgagtcggtgaccaatg 3180 V.5 3121 ctgattctctcttcagtgttgtaattgtcaatctgttcgtgaatgagtcggtgaccaatg 3180 V.1 3181 ctacactgattaatgaactggtgcgcaaaagcactgaagcaccagtgaccccaaatactg 3240 V.5 3181 ctacactgattaatgaactggtgcgcaaaagcactgaagcaccagtgaccccaaatactg 3240 V.1 3241 agatagctgatgtatcctcaccaactagtgactatgtcaagatcctggttgcagctgttg 3300 V.5 3241 agatagctgatgtatcctcaccaactagtgactatgtcaagatcctggttgcagctgttg 3300 WO 2004/098515 PCT/US2004/013568 272 V.1 3301 ctggcaccataactgtcgttgtagttattttcatcactgctgtagtaagatgtcgccagg 3360 IIIIIIiIIiI IiII|IIi ii|I|liIiiIiiIliiiIiiiiIII I 11 11I 1 1 1i1 1 i11 i i11 1 11 1 11 1 I i i i I V.5 3301 ctggcaccataactgtcgttgtagttattttcatcactgctgtagtaagatgtcgccagg 3360 V.1 3361 caccacaccttaaggctgctcagaaaaacaagcagaattctgaatgggctaccccaaacc 3420 1111I1I 11 111111111111l1111 II Ii lI 1 I 1 II I11II1 I I|lI| I l I l I I Ii1I1i1 i1 I V.5 3361 caccacaccttaaggctgctcagaaaaacaagcagaattctgaatgggctaccccaaacc 3420 V.1 3421 cagaaaacaggcagatgataatgatgaagaaaaagaaaaagaagaagaagcattccccta 3480 I i i I I I |I| |I iIi I I 1I1I1I i I I1 I I 1I 11 l I1i1 l I 11ll I 1| I1 I l1 i11I V.5 3421 cagaaaacaggcagatgataatgatgaagaaaaagaaaaagaagaagaagcattccccta 3480 V.1 3481 agaacttgctgcttaattttgtcactattgaagaaactaaggcagatgatgttgacagtg 3540 V.5 3481 agaacttgctgcttaattttgtcactattgaagaaactaaggcagatgatgttgacagtg 3540 V.1 3541 atggaaacagagtcacactagaccttcctattgatctagaagagcaaacaatgggaaagt 3600 11 111I1I11 11111I1111I 1111| l1I II I I IlIIIlIIIIIII I I I Il III 1 |1 II I I V.5 3541 atggaaacagagtcacactagaccttcctattgatctagaagagcaaacaatgggaaagt 3600 V.1 3601 acaattgggtaactacacctactactttcaagcccgacagccctgatttggcccgacact 3660 |111111 lIlI II II il l l11111 11111111111l I 111111111l 1 Il I Il I1 l II 1I1 V.5 3601 acaattgggtaactacacctactactttcaagcccgacagccctgatttggcccgacact 3660 V.1 3661 acaaatctgcctctccacagcctgccttccaaattcagcctgaaactcccctgaattcga 3720 i 11111 1 111 1 il 1II i Ii 11I 1 I I jilIl Ji l l I 11 I1 iI II l11I I1l1 111I I V.5 3661 acaaatctgcctctccacagcctgccttccaaattcagcctgaaactcccctgaattcga 3720 V.1 3721 agcaccacatcatccaagaactgcctctcgataacacctttgtggcctgtgactctatct 3780 V.5 3721 agcaccacatcatccaagaactgcctctcgataacacctttgtggcctgtgactctatct 3780 V.1 3781 ccaagtgttcctcaagcagttcagatccctacagcgtttctgactgtggctatccagtga 3840 Il 111111I11I111 11|I1 III 111IlII 111iiI I 1iI 1 I I ||| l I 1111 lI|1 I V.5 3781 ccaagtgttcctcaagcagttcagatccctacagcgtttctgactgtggctatccagtga 3840 V.1 3841 cgaccttcgaggtacctgtgtccgtacacaccagaccg 3878 V.5 3841 cgaccttcgaggtacctgtgtccgtacacaccagaccg 3878 Table LIV(d). Peptide sequences of protein coded by 109P1D4 v.5 (SEQ ID NO: 258) MDLLSGTYIF AVLLACVVFH SGAQEKNYTI REEMPENVLI GDLLKDLNLS LIPNKSLTTA 60 MQFKLVYKTG DVPLIRIEED TGEIFTTGAR IDREKLCAGI PRDEHCFYEV EVAILPDEIF 120 RLVKIRFLIE DINDNAPLFP ATVINISIPE NSAINSKYTL PAAVDPDVGI NGVQNYELIK 180 SQNIFGLDVI ETPEGDKMPQ LIVQKELDRE EKDTYVMKVK VEDGGFPQRS STAILQVSVT 240 DTNDNHPVFK ETEIEVSIPE NAPVGTSVTQ LHATDADIGE NAKIHFSFSN LVSNIARRLF 300 HLNATTGLIT IKEPLDREET PNHKLLVLAS DGGLMPARAM VLVNVTDVND NVPSIDIRYI 360 VNPVNDTVVL SENIPLNTKI ALTTVTDKDA DHNGRVTCFT DHEIPFRLRP VFSNQFLLET 420 AAYLDYESTK EYAIKLLAAD AGKPPLNQSA MLFIKVKDEN DNAPVFTQSF VTVSIPENNS 480 PGIQLTKVSA MDADSGPNAK INYLLGPDAP PEFSLDCRTG MLTVVKKLDR EKEDKYLFTI 540 LAKDNGVPPL TSNVTVFVSI IDQNDNSPVF THNEYNFYVP ENLPRHGTVG LITVTDPDYG 600 DNSAVTLSIL DENDDFTIDS QTGVIRPNIS FDREKQESYT FYVKAEDGGR VSRSSSAKVT 660 INVVDVNDNK PVFIVPPSNC SYELVLPSTN PGTVVFQVIA VDNDTGMNAE VRYSIVGGNT 720 RDLFAIDQET GNITLMEKCD VTDLGLHRVL VKANDLGQPD SLFSVVIVNL FVNESVTNAT 780 LINELVRKST EAPVTPNTEI ADVSSPTSDY VKILVAAVAG TITVVVVIFI TAVVRCRQAP 840 WO 2004/098515 PCT/US2004/013568 273 HLKAAQKNKQ NSEWATPNPE NRQMIMMKKK KKKKKHSPKN LLLNFVTIEE TKADDVDSDG 900 NRVTLDLPID LEEQTMGKYN WVTTPTTFKP DSPDLARHYK SASPQPAFQT QPETPLNSKH 960 HIIQELPLDN TFVACDSISK CSSSSSDPYS VSDCGYPVTT FEVPVSVHTR PSQRRVTFHL 1020 PEGSQESSSD GGLGDHDAGS LTSTSHGLPL GYPQEEYFDR ATPSNRTEGD GNSDPESTFI 1080 PGLKKAAEIT VQPTVEEASD NCTQECLIYG HSDACWMPAS LDHSSSSQAQ ASALCHSPPL 1140 SQASTQHHSP RVTQTIALCH SPPVTQTIAL CHSPPPIQVS ALHHSPPLVQ ATALHHSPPS 1200 AQASALCYSP PLAQAAAISH SSPLPQVIAL HRSQAQSSVS LQQGWVQGAD GLCSVDQGVQ 1260 GSATSQFYTM SERLHPSDDS IKVIPLTTFT PRQQARPSRG DSPIMEEHPL 1310 Table LV(d). Amino acid sequence alignment of 109P1D4 v.1 (SEQ ID NO: 259) and I09PID4 v.5 (SEQ ID NO: 260) Score 2005 bits (5195), Expect = 0.0identities = 1011/1011 (100%), Positives = 1011/1011 (100%) V.1 1 MDLLSGTYIFAVLLACVVFHSGAQEKNYTIREEMPENVLIGDLLKDLNLSLIPNKSLTTA 60 MDLLSGTYIFAVLLACVVFHSGAQEKNYTIREEMPENVLIGDLLKDLNLSLIPNKSLTTA V.5 1 MDLLSGTYIFAVLLACVVFHSGAQEKNYTIREEMPENVLIGDLLKDLNLSLIPNKSLTTA 60 V.1 61 MQFKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIF 120 MQFKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIF V.5 61 MQFKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIF 120 V.1 121 RLVKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIK 180 RLVKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIK V.5 121 RLVKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIK 180 V.1 181 SQNIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVT 240 SQNIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVT V.5 181 SQNIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVT 240 V.1 241 DTNDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLF 300 DTNDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLF V.5 241 DTNDNHPVFKETEIEVSIPENAPVGTSVTQL-ATDADIGENAKIHFSFSNLVSNIARRLF 300 V.1 301 HLNATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYI 360 HLNATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYI V.5 301 HLNATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYI 360 V.1 361 VNPVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLET 420 VNPVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLET V.5 361 VNPVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLET 420 V.1 421 AAYLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNS 480 AAYLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNS V.5 421 AAYLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNS 480 V.1 481 PGIQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTVVKKLDREKEDKYLFTI 540 PGIQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTVVKKLDREKEDKYLFTI V.5 481 PGIQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTVVKKLDREKEDKYLFTI 540 V.1 541 LAKDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYG 600 LAKDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYG V.5 541 LAKDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYG 600 V.1 601 DNSAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVT 660 DNSAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVT V.5 601 DNSAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVT 660 V.1 661 INVVDVNDNKPVFIVPPSNCSYELVLPSTNPGTVVFQVIAVDNDTGMNAEVRYSIVGGNT 720 INVVDVNDNKPVFIVPPSNCSYELVLPSTNPGTVVFQVIAVDNDTGMNAEVRYSIVGGNT V.5 661 INVVDVNDNKPVFIVPPSNCSYELVLPSTNPGTVVFQVIAVDNDTGMNAEVRYSIVGGNT 720 V.1 721 RDLFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSVVIVNLFVNESVTNAT 780 RDLFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSVVIVNLFVNESVTNAT V.5 721 RDLFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSVVIVNLFVNESVTNAT 780 V.1 781 LINELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVVVVIFITAVVRCRQAP 840 LINELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVVVVIFITAVVRCRQAP V.5 781 LINELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVVVVIFITAVVRCRQAP 840 WO 2004/098515 PCT/US2004/013568 274 v.1 841 HLKAAQKNKQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDG 900 HLKAAQKNKQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDG v.5 841 HLKAAQKNKQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDG 900 V.1 901 NRVTLDLPIDLEEQTMGKYNWVTTPTTFKPDSDLARHYKSASPQPAFQIQPETPLNSKH 960 NRVTLDLPTDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNSKH V.5 901 NRVTLDL2IDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNSKH 960 V.1 961 HIIQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP 1011 HIIQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP V.5 961 HIIQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP 1011 Table Ll(e). Nucleotide sequence of transcript variant 109P1 D4 v.6 (SEQ ID NO: 261) ggcagtcggc gaactgtctg ggcgggagga gccgtgagca gtagctgcac tcagctgccc 60 gcgcggcaaa gaggaaggca agccaaacag agtgcgcaga gtggcagtgc cagcggcgac 120 acaggcagca caggcagccc gggctgcctg aatagcctca gaaacaacct cagcgactcc 180 ggctgctctg cggactgcga gctgtggcgg tagagcccgc tacagcagtc gcagtctccg 240 tggagcgggc ggaagccttt tttctccctt tcgtttacct cttcattcta ctctaaaggc 300 atcgttatta gagggtgctt aaaaagtaca gatcaactgg atggatgaat ggatggaaga 360 ggatggaata tcttaacaaa acacattttc cttaagtaaa ttcatgcata ctccaaataa 420 aatacagaat gtgaagtatc tctgaactgt gctgttgaat atggtagcta ctagctacat 480 gaaaatcctg ttgtgaataa gaaggattcc acagatcaca taccaqagcg gttttgcctc 540 agctgctctc aactttgtaa tcttgtgaag aagctgacaa gcttggctga ttgcagtgca 600 ctatgaggac tgaatgacag tgggttttaa ttcagatatt tcaagtgttg tgcgcgttaa 660 tacaacaaac tgtcacaagt gtttgttgtc cgqacgtac attttcgcgg tctgctagt 720 atgcgtgqtg ttccactctg gcgcccagqa gaaaaactac accatccgag aagaaattcc 780 agaaaacgtc ctgataggca acttgttgaa aaccttaac ttgtcgctga ttccaaacaa 840 gtccttgaca actactatgc agttcaagct agtgtacaag accggagatg tgccactgat 900 tcgaattgaa gaggatactg qtgagatctt cactaccggc gctcgcattg atcgtgagaa 960 attatgtgct ggtatcccaa gggatgagca ttgcttttat gaagtggagg ttgccatttt 1020 gccggatgaa atatttagac tggttaagat acgttttctg atagaagata taaatgataa 1080 tgcaccattg ttcccagcaa cagttatcaa catatcaatt ccagagaact cggctataaa 1140 ctctaaatat actctcccag cggctgttga tcctgacgta ggcataaacg gagttcaaaa 1200 ctacjaacta attaagagtc aaaacatttt tggcctcgat gtcattgaaa caccagaagg 1260 agacaagatg ccacaactga ttgttcaaaa ggagttagat agggaagaga aggataccta 1320 tgtgatgaaa gtaaaggttq aagatagtgg ctttcctcaa agatccagta ctgctatttt 1380 gcaagtaagt gttactgata caaatgacaa ccacccagtc tttaaggaga cagagattga 1440 agtcagtata ccagaaaatg ctcctgtagg cacttcagtg acacagctcc atgccacaga 1500 tgctgacata ggtgaaaatg ccaagatcca cttctctttc agcaatctag tctccaacat 1560 tgccaggaga ttatttcacc tcaatgccac cactggactt atcacaatca aagaaccact 1620 ggatagggaa gaaacaccaa accacaagtt actggttttg gcaagtgatg gtggattgat 1680 gccagcaaga gcaatggtgc tggtaaatgt tacagatgtc aatgataatg tcccatccat 1740 tqacataaga tacatcgtca atcctgtcaa tgacacagtt gttctttcag aaaatattcc 1800 actcaaca c aaaattgctc tcataactgt gacggataag gatgcggacc ataatggcag 1860 ggtgacatgc ttcacagatc atgaaattcc tttcagatta aggccagtat tcagtaatca 1920 gttcctcctg gagaatgcag catatcttga ctatgagtcc acaaaagaat atgccattaa 1980 attactggct gcagatgctg gcaaacctcc tttgaaizcag tcagcaatgc tcttcatcaa 2040 agtgaaagat gaaaatgaca atgctccagt tttcacccag tctttcgtaa ctgtttctat 2100 tcctgagaat aactctcctg gcatccagtt gatgaaagta agtgcaacgg atgcagacag 2160 tgggcctaat gctgagatca attacctgct aggccctgat gctccacctg aattcagcct 2220 ggatcgtcgt acaggcatgc tgactgtagt gaagaaacta gatagagaaa aagaggataa 2280 atatttattc acaattctgg caaaagataa tqgggtacca cccttaacca qcaatgtcac 2340 agtctttgta agcattattg atcagaatga caatagccca gttttcactc acaatgaata 2400 caaattctat gtcccagaaa accttccaag gcatggtaca gtaggactaa tcactgtaac 2460 tcatcctgat tatggagaca attctgcagt tacgctctcc attttagatg agaatgatga 2520 cttcaccatt gattcacaaa ctggtgtcat ccgaccaaat atttcatttg atagagaaaa 2580 acagaatct tacactttct atgtaaaggc tgaggatggt ggtagagtat cacgttcttc 2640 aagtgccaaa gtaaccataa atgtggttga tgtcaatgac aacaaaccag ttttcattgt 2700 ccctccttac aactattctt atgaattqgt tctaccgtcc actaatccag gcacagtggt 2760 gtttcaggta attgctgttg acaatgacac tggcatgaat gcagaggttc gttacagcat 2820 tgtaggagga aacacaagag atctgtttgc aatcgaccaa gaaacaggca acataacatt 2880 gatggagaaa tgtgatgtta cagaccttgg tttacacaga gtgttggtca aagctaatga 2940 WO 2004/098515 PCT/US2004/013568 275 cttaggacag cctgattctc tcttcagtgt tgtaattgtc aatctgttcg tgaatgagtc 3000 agtgaccaat gctacactga ttaatgaact ggtgcgcaaa agcattgaag caccagtgac 3060 cccaaatact gagatagctg atgtatcctc accaactagt gactatgtca agatcctggt 3120 tgcagctgtt gctggcacca taactgtcgt tgtagttatt ttcatcactg ctgtagtaag 3180 atgtcgccag gcaccacacc ttaagqctgc tcagaaaaac atgcagaatt ctqaatggc 3240 taccccaaac ccagaaaaca ggcagatgat aatgatgaag aaaaagaaaa agaagaagaa 3300 gcattcccct aagaacctgc tgcttaattt tgtcactatt gaagaaacta aggcagatga 3360 tgttgacagt gatggaaaca gagtcacact agaccttcct attgatctag aagagcaaac 3420 aatgggaaag tacaattqgg taactacacc tactactttc aagcctgaca gccctgattt 3480 ggcccgacac tacaaatctg cctctccaca gcctqccttc caaattcaqc ctgaaactcc 3540 cctgaatttg aagcaccaca tcatccaaga actgcctctc gataacacct ttgtggcctg 3600 tgactctatc tccaagtgtt cctcaagcag ttcagatccc tacagcgttt ctgactgtgg 3660 ctatccagtg acaaccttcg aggtacctgt gtccgtacac accagaccga ctgattceag 3720 gacatgaact attgaaatct gcagtgagat gtaactttct aggaacaaca aaattccatt 3780 ccccttccaa aaaatttcaa tggattgtqa tttcaaaatt aggctaagat cattaatttt 3840 gtaatctaga tttcccatta taaaagcaag caaaaatcat cttaaaaatg atgtcctagt 3900 gaaccttgtg ctttctttaq ctgtaatctg gcaatggaaa tttaaaattt atggaagaga 3960 cagtgcagca caataacaga gtactctcat gctgtttctc tgtttgctct gaatcaacag 4020 ccatgatgta atataaggct gtcttggtgt atacacttat ggttaatata tcagtcatga 4080 aacatgcaat tacttgccct gtctqattgt tgaataatta aaacattatc ttccaggagt 4140 ttggaagtga qctgaactaq ccaaactact ctctgaaagg tatccagggc aagagacatt 4200 tttaagaccc caaacaaaca aaaaacaaaa ccaaaacact ctggttcagt gttttgaaaa 4260 tattcactaa cataatattg ctgagaaaat catttttatt acccaccact ctgcttaaaa 4320 gttgagtggg ccgggcgcgg tggctcacgc ctgtaatccc agcactttgg gaggccgagg 4380 cgggtggatc acaggtcag gagattgaga ccatcctggc taacacggtg aaaccccatc 4440 tccactaaaa atacaaaaaa ttagcctggc gtgctcgcgg gcgcctgtag tcccagctac 4500 tcgggaggct gaggcaggag aatagcgtga acccgggagg cggagcttgc agtgagccga 4560 gatggcgcca ctctgcactc cagcctgggt gacagagcaa gactctgtct caaaaagaaa 4620 aaaatgttca atgatagaaa ataattttac taggttttta tgttgattgt actcatggtg 4680 ttccactcct tttaattatt aaaaagttat ttttggggtg ggtgtggtgg ctcacaccgt 4740 aatcccagca cttgggagg ccgaggtggg tggatcacct gaggtcagga gttcaagacc 4800 agtntggcca acatggcgaa accccgtttt 4830 Table 1-II1(e). Nucleotide sequence alignment of 109P1 D4 v.1 (SEQ ID NO: 262) and 109PI D4 v.6 (SEQ ID NO: 263) Score =5676 bits (2952), Expect = 0.identities =3002/3027 (99%) Strand = Plus / Plus V. 1 852 ttgttgtccgggacgtacattttcgcggtcctgctagcatgcgtggtgttccactctggc 911 V.6 683 ttgttgtccgggacgtacattttcgcggtcctgctagtatgcgtggtgttccactctggc 742 V.1 912 gcccaggagaaaaactacaccatccgagaagaaatgccagaaaacgtcctgataggCgac 971 V.6 743 gcccaggagaaaaactacaccatccgagaagaaattccagaaaacgtcctgataggcaac 802 V.1 972 ttgttgaaagaccttaacttgtcgctgattccaaacaagtccttgacaactgctatgcag 1031 V.6 803 ttgttgaaagaccttaacttgtcgctgattccaaacaagtccttgacaactactatgcag 862 V.1 1032 ttcaagctagtgtacaagaccggagatgtgccactgattcgaattgaagaggatactggt 1091 V.6 863 ttcaagctagtgtacaagaccggagatgtgccactgattcgaattgaagaggatactggt 922 V.1 1092 gagatcttcactactggcgctcgcattgatcgtgagaaattatgtgctggtatcccaagg 1151 V.6 923 gagatcttcactaccggcgctcgcattgatcgtgagaaattatgtgctggtatcccaagg 982 V.1 1152 gatgagcattgcttttatgaagtggaggttgccattttgccggatgaaatatttagactg 1211 V.6 983 gatgagcattgcttttatgaagtggaggttgccattttgccggatgaaatatttagactg 1042 WO 2004/098515 PCT/US2004/013568 276 V.1 1212 gttaagatacgttttctgatagaagatataaatgataatgcaccattgttcccagcaaca 1271 Ii 1111111l il 1llIll 11ll 11111 !11111111 1Illllllll1 iIllllll illl V.6 1043 gttaagatacgttttctgatagaagatataaatgataatgcaccattgttcccagcaaca 1102 V.1 1272 gttatcaacatatcaattccagagaactcggctataaactctaaatatactctcccagcg 1331 I 1IiiI l i i I 1 I 111i 111111111 II lI iI1 l i |I l i i | I i I I |||1 I 1 I|| V.6 1103 gttatcaacatatcaattccagagaactcggctataaactctaaatatactctcccagcg 1162 V.1 1332 gctgttgatcctgacgtaggaataaacggagttcaaaactacgaactaattaagagtcaa 1391 li I Ill il1 1 1111111 11 1 illlll 1Il 1I1lllll 1lllllll llll 1 1 1111111 V.6 1163 gctgttgatcctgacgtaggcataaacggagttcaaaactacgaactaattaagagtcaa 1222 V.1 1392 aacatttttggcctcgatgtcattgaaacaccagaaggagacaagatgccacaactgatt 1451 IlIl illiiil||111 111111Il 1 il lll ll1lll ll I ll i ll ll I II V.6 1223 aacatttttggcctcgatgtcattgaaacaccagaaggagacaagatgccacaactgatt 1282 V.1 1452 gttcaaaaggagttagatagggaagagaaggatacctacgtgatgaaagtaaaggttgaa 1511 Il11111111111111111| l l ll l l l Il 11lilllllli 11lll llll i V.6 1283 gttcaaaaggagttagatagggaagagaaggatacctatgtgatgaaagtaaaggttgaa 1342 V.1 1512 gatggtggctttcctcaaagatccagtactgctattttgcaagtgagtgttactgataca 1571 l11 Illli1 111 ||11111111111111111111ill lll ll i Illilillillllli V.6 1343 gatggtggctttcctcaaagatccagtactgctattttgcaagtaagtgttactgataca 1402 V.1 1572 aatgacaaccacccagtctttaaggagacagagattgaagtcagtataccagaaaatgct 1631 Il11 I111 11 1 1 1 1 1 ii 1l ll ll l i ll ll1ll l ll ll ll i ll Il ill Ill1 Illlll Il V.6 1403 aatgacaaccacccagtctttaaggagacagagattgaagtcagtataccagaaaatgct 1462 V.1 1632 cctgtaggcacttcagtgacacagctccatgccacagatgctgacataggtgaaaatgcc 1691 [1 1 l il 11 111111|11 1 1 1 1 1111111111 l ll ll ll lil 1l ill lllll V.6 :1463 cctgtaggcacttcagtgacacagctccatgccacagatgctgacataggtgaaaatgcc 1522 V.1 1692 aagatccacttctctttcagcaatctagtctccaacattgccaggagattatttcacctc 1751 l 11111 111 Ill l ll i lllll ill ll l ll lll lll lll 111111 1 l il l ll lll l|1 V.6 1523 aagatccacttctctttcagcaatctagtctccaacattgccaggagattatttcacctc 1582 V.1 1752 aatgccaccactggacttatcacaatcaaagaaccactggatagggaagaaacaccaaac 1811 V.6 1583 aatgccaccactggacttatcacaatcaaagaaccactggatagggaagaaacaccaaac 1642 V.1 1812 cacaagttactggttttggcaagtgatggtggattgatgccagcaagagcaatggtgctg 1871 V.6 1643 cacaagttactggttttggcaagtgatggtggattgatgccagcaagagcaatggtgctg 1702 V.1 1872 gtaaatgttacagatgtcaatgataatgtcccatccattgacataagatacatcgtcaat 1931 V.6 1703 gtaaatgttacagatgtcaatgataatgtcccatccattgacataagatacatcgtcaat 1762 V.1 1932 cctgtcaatgacacagttgttctttcagaaaatattccactcaacaccaaaattgctctc 1991 l 1 11 11 1 111| 111 1lll ll lll ll l l 1111 111111 l1 1 i ll i 1l lll ll l l V.6 1763 cctgtcaatgacacagttgttctttcagaaaatattccactcaacaccaaaattgctctc 1822 V.1 1992 ataactgtgacggataaggatgcggaccataatggcagggtgacatgcttcacagatcat 2051 | 1 1 1 | I l l i l ll l l ll l l l l l l l l l l l l l l l l l I l l i I l l i l l l l1 1 1 1 1 1 1 I l l WO 2004/098515 PCT/US2004/013568 277 v.6 1823 ataactgtgacggataaggatgcggaccataatggcagggtgacatgcttcacagatcat 1882 V.1 2052 gaaatccctttcagattaaggccagtattcagtaatcagttcctcctggagactgcagca 2111 l ii l I iI I 1111ll111ill I111111111111 11111 111 II I I II I lI1 V.6 1883 gaaattcctttcagattaaggccagtattcagtaatcagttcctcctggagaatgcagca 1942 V.1: 2112 tatcttgactatgagtccacaaaagaatatgccattaaattactggctgcagatgctggc 2171 V.6 1943 tatcttgactatgagtccacaaaagaatatgccattaaattactggctgcagatgctggc 2002 V.1 2172 aaacctcctttgaatcagtcagcaatgctcttcatcaaagtgaaagatgaaaatgacaat 2231 111| 11 1 I lll i il | I 11 111 1111 lI II 11 l 11 II 1i V.6 2003 aaacctcctttgaatcagtcagcaatgctcttcatcaaagtgaaagatgaaaatgacaat 2062 V.1 2232 gctccagttttcacccagtctttcgtaactgtttctattcctgagaataactctcctggc 2291 111 111 11l 1111l 11I1l| 1111 11 li ll 1Il I I l I|II 1l 111i I| IlI II II I I I I1l V.6 2063 gctccagttttcacccagtctttcgtaactgtttctattcctgagaataactctcctggc 2122 V.1 2292 atccagttgacgaaagtaagtgcaatggatgcagacagtgggcctaatgctaagatcaat 2351 11I11111l11 I lIi1 I I lilil l l lI lI| lI I 11 1 11 1 11I|1 111||||111 V.6 2123 atccagttgatgaaagtaagtgcaacggatgcagacagtgggcctaatgctgagatcaat 2182 V.1 2352 tacctgctaggccctgatgctccacctgaattcagcctggattgtcgtacaggcatgctg 2411 l lI I l 1 11 11 1 1111l1 I II | I l I 1 11 II II I I|i V.6 2183 tacctgctaggccctgatgctccacctgaattcagcctggatcgtcgtacaggcatgctg 2242 V.1 2412 actgtagtgaagaaactagatagagaaaaagaggataaatatttattcacaattctggca 2471 I lI l I i I l I | I il l I I I 1 1 1 l l | | I I I I I I II l 11I1l 1 I 1 I I V.6 2243 actgtagtgaagaaactagatagagaaaaagaggataaatatttattcacaattetggca 2302 V.1 2472 aaagataacggggtaccacccttaaccagcaatgtcacagtctttgtaagcattattgat 2531 V.6 2303 aaagataatggggtaccacccttaaccagcaatgtcacagtctttgtaagcattattgat 2362 V.1 2532 cagaatgacaatagcccagttttcactcacaatgaatacaacttctatgtcccagaaaac 2591 1l 111111111I|1 IIlII lI II II1111I11|1 I I1 II11 II II liI I~liii V.6 2363 cagaatgacaatagcccagttttcactcacaatgaatacaaattctatgtcccagaaaac 2422 V.1 2592 cttccaaggcatggtacagtaggactaatcactgtaactgatcctgattatggagacaat 2651 lIIl I IlIllII IIll l i Ililli |111 11 1 j il I I I I I 1 1 I I V.6 2423 cttccaaggcatggtacagtaggactaatcactgtaactgatcctgattatggagacaat 2482 V.1 2652 tctgcagttacgctctccattttagatgagaatgatgacttcaccattgattcacaaact 2711 ii I III I I I IllII I lII l l lil1 1111 11111i I lIIIII I II II|II I l I1 V.6 2483 tctgcagttacgctctccattttagatgagaatgatgacttcaccattgattcacaaact 2542 V.1 2712 ggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatcttacactttctat 2771 V.6 2543 ggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatcttacactttctat 2602 V.1 2772 gtaaaggctgaggatggtggtagagtatcacgttcttcaagtgccaaagtaaccataaat 2831 11 1 1 ||1lili I Il lil ilil I l 111 IIIl1 I I I I|1 1 ||I l|I I1 I I1 I l V.6 2603 gtaaaggctgaggatggtggtagagtatcacgttcttcaagtgccaaagtaaccataaat 2662 V.1 2832 gtggttgatgtcaatgacaacaaaccagttttcattgtccctccttccaactgttcttat 2891 WO 2004/098515 PCT/US2004/013568 278 | I|1 I ii I IIi I 111I 1111 1 1I 1 I l 1111111 V. 6 2663 gtggttgatgtcaatgacaacaaaccagttttcattgtccctccttacaactattcttat 2722 V.1 2892 gaattggttctaccgtccactaatccaggcacagtggtctttcaggtaattgctgttgac 2951 li 111Il llII IlIIiiI111 iIII I I111 11111111111 ji II 11111 1I V.6 2723 gaattggttctaccgtccactaatccaggcacagtggtctttcaggtaattgctgttgac 2782 V.1 2952 aatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaaacacaagagat 3011 Il |Il IiiI Ilii II i I 11 111 11 1 11 ii Ili 11111| 1| 1 1 ||11 11 11 l| || |ii V.6 2783 aatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaaacacaagagat 2842 V.1 3012 ctgtttgcaatcgaccaagaaacaggcaacataacattgatggagaaatgtgatgttaca 3071 V.6 2843 ctgtttgcaatcgaccaagaaacaggcaacataacattgatggagaaatgtgatgttaca 2902 V.1 3072 gaccttggtttacacagagtgttggtcaaagctaatgacttaggacagcctgattctctc 3131 V.6 : 2903 gaccttggtttacacagagtgttggtcaaagctaatgacttaggacagcctgattctctc 2962 V.1 : 3132 ttcagtgttgtaattgtcaatctgttcgtgaatgagtcggtgaccaatgctacactgatt 3191 I11 111I11111111111 Iil IiI lII III 1111111|1 1 II II| I |11 I | I|1 lIi I V.6 : 2963 ttcagtgttgtaattgtcaatctgttcgtgaatgagtcagtgaccaatgctacactgatt 3022 V.1 3192 aatgaactggtgcgcaaaagcactgaagcaccagtgaccccaaatactgagatagctgat 3251 l iIiI Il lI l l i | I | 11I 1I 111 i 11 11|1 lIi I I II 1I 1I Il I 1I1II 1I I| V.6 3023 aatgaactggtgcgcaaaagcattgaagcaccagtgaccccaaatactgagatagctgat 3082 V.1 3252 gtatcctcaccaactagtgactatgtcaagatcctggttgcagctgttgCtggcaccata 3311 1 l i ii i 111111i 11 I lI lI I 1 I I11 Ii lI II II I111 I I 111 I |11 I1l V.6 3083 gtatcctcaccaactagtgactatgtcaagatcctggttgcagctgttgctggcaccata 3142 V.1 3312 actgtcgttgtagttattttcatcactgctgtagtaagatgtcgccaggcaccacacctt 3371 V.6 3143 actgtcgttgtagttattttcatcactgctgtagtaagatgtcgccaggcaccacacctt 3202 V.1 3372 aaggctgctcagaaaaacaagcagaattctgaatgggctaccccaaacccagaaaacagg 3431 111111111|111111111 1 I I l l1ll 1l1illll1l l l ii ll l l ll ll ll lll ll1 V.6 3203 aaggctgctcagaaaaacatgcagaattctgaatgggctaccccaaacccagaaaacagg 3262 V.1 3432 cagatgataatgatgaagaaaaagaaaaagaagaagaagcattcccctaagaacttgctg 3491 I l I I l l l 111Il I I I iI I | III II ii 1 i I 111 H il V.6 3263 cagatgataatgatgaagaaaaagaaaaagaagaagaagcattcccctaagaacctgctg 3322 V.1 3492 cttaattttgtcactattgaagaaactaaggcagatgatgttgacagtgatggaaacaga 3551 V.6 3323 cttaattttgtcactattgaagaaactaaggcagatgatgttgacagtgatggaaacaga 3382 V.1 3552 gtcacactagaccttcctattgatctagaagagcaaacaatgggaaagtacaattgggta 3611 1I| IIII |111 1 1 1 11 1 1 1 1 11 1 11l11 1 1 1 I l I IIII| II| I II I 1 I II V.6 3383 gtcacactagaccttcctattgatctagaagagcaaacaatgggaaagtacaattgggta 3442 V.1 3612 actacacctactactttcaagcccgacagccctgatttggcccgacactacaaatctgcc 3671 V.6 3443 actacacctactactttcaagcctgacagccctgatttggcccgacactacaaatctgcc 3502 WO 2004/098515 PCT/US2004/013568 279 v.1 : 3672 tctccacagcctgccttccaaattcagcctgaaactcccctgaattcgaagcaccacatc 3731 l1111l ll11 l ll1 1111l1 l ll llllll ll11111111|1111 11111 I[ii I 1111111111 V.6 : 3503 tctccacagcctgccttccaaattcagcctgaaactcccctgaatttgaagcaccacatc 3562 V.1 : 3732 atccaagaactgcctctcgataacacctttgtggcctgtgactctatctccaagtgttcc 3791 l lIl lll I II i 1 l 1I I l II II1 IIl 1111 I I Ilil Il Ill1 l 1 Il1 il l1 l l i V.6 : 3563 atccaagaactgcctctcgataacacctttgtggcctgtgactctatctccaagtgttcc 3622 V.1 : 3792 tcaagcagttcagatccctacagcgtttctgactgtggctatccagtgacgaccttcgag 3851 l i l 1 l ll ll l l l ll ll l 1 l l l l 1111111 11111111|| l1 1 illl I i V.6 : 3623 tcaagcagttcagatccctacagcgtttctgactgtggctatccagtgacaaccttcgag 3682 V.1 : 3852 gtacctgtgtccgtacacaccagaccg 3878 V.6 : 3683 gtacctgtgtccgtacacaccagaccg 3709 Table LIV(e). Peptide sequences of protein coded by 109P1D4 v.6 (SEQ ID NO: 264) MTVGFNSDIS SVVRVNTTNC HKCLLSGTYI FAVLLVCVVF HSGAQEKNYT IREEIPENVL 60 IGNLLKDLNL SLIPNKSLTT TMQFKLVYKT GDVPLIRIEE DTGEIFTTGA RIDREELCAG 120 IPRDEHCFYE VEVAILPDEI FRLVKIRFLI EDINDNAPLF PATVINISIP ENSAINSKYT 180 LPAAVDPDVG INGVQNYELI KSQNIFGLDV IETPEGDKMP QLIVQKELDR EEKDTYVMKV 240 KVEDGGFPQR SSTAILQVSV TDTNDNHPVF KETEIEVSIP ENAPVGTSVT QLHATDADIG 300 ENAKIHFSFS NLVSNIARRL FHLNATTGLI TIKEPLDREE TPNHKLLVLA SDGGLNFARA 360 MVLVNVTDVN DNVPSIDIRY IVNPVNDTVV LSENIPLNTK IALITVTDKD ADHNGRVTCF 420 TDHEIPFRLR PVFSNQFLLE NAAYLDYEST KEYATKLLAA DAGKPPLNQS AMLFIKVKDE 480 NDNAPVFTQS FVTVSIPENN SPGIQLMKVS ATDADSGPNA EINYLLGPDA PPEFSLDRRT 540 GMLTVVKKLD REKEDKYLFT ILAKDNGVPP LTSNVTVFVS IIDQNDNSPV FTHNEYKFYV 600 PENLPRHGTV GLITVTDPDY GDNSAVTLSI LDENDDFTID SQTGVIRPNI SFDREKQESY 660 TFYVKAEDGG RVSRSSSAKV TINVVDVNDN KPVFIVPPYN YSYELVLPST NPGTVVFQVI 720 AVDNDTGMNA EVRYSIVGGN TRDLFAIDQE TGNITLMEKC DVTDLGLHRV LVKANDLGQP 780 DSLFSVVIVN LFVNESVTNA TLINELVRKS IEAPVTPNTE TADVSSPTSD YVKILVAAVA 840 GTITVVVVIF TTAVVRCRQA PHLKAAQKNM QNSEWATPNP ENRQMIMMKK KKKKKKHSPK 900 NLLLNFVTIE ETKADDVDSD GNRVTLDLPI DLEEQTMGKY NWVTTPTTFK PDSPDLARHY 960 KSASPQPAFQ IQPETPLNLK HHIIQELPLD NTFVACDSIS KCSSSSSDPY SVSDCGYPVT 1020 TFEVPVSVHT RPTDSRT 1037 Table LV(e). Amino acid sequence alignment of 109P1 04 v. (SEQ ID NO: 265) and 1 09PI D4 v.6 (SEQ ID NO: 266) Score 1966 bits (5093), Expect = D.0ldentities = 994/1009 (98%), Positives = 997/1009 (98%) V.1 3 LLSGTYIFAVLLACVVFHSGAQEKNYTIREEMPENVLIGDLLIDLNLLIPNKSLTTQ 62 LLSGTYIFAVLL CVVFHSGAQKNYTIREE±PENVLIG+LLKDLNLSLIPNKSLTT MQ V. 6 24 LLSGTYTFAVLLVCVVFHSGAQEKNYTIREEIPENVLIGNLLKDLNLSLIPNKSLTTTMQ 83 V.1 63 FKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCACIGRDEHCFYEVEVAILPDEIFRL 122 FKLVYKTGDVPLIRIEEDTGEI FTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEI FRL V. 6 84 FKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIFRL 143 V.1 123 VKIRFLIEDINDNA2LFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIKSQ 182 VKIRFLIED INDNAPLFPATVINIS IPENSAINSKYTLPAAV7DPDVGINGVQNYELIKSQ V.6 144 VKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIKSQ 203 V.1 183 NIFGLDVIETPEGDKMPQLIVQKELDREEEDTYVMKVKVEDGGFPQRSSTAILQVSVTDT 242 NI FGLDVIETPEGDI MPQLIVQKELDREEI<DTYVMKVKVEDGGFPQRS STAILQVSV'DT V.6 204 NIFGLDVIETPEGDKMPQLTVQKELDREEI DTYVMNKVKVEDGGFPQRSSTAILQVSVTDT 263 V.1 243 NDNHPVFKET9IEVSIQENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARLFHL 302 NDNHPVFKETEIEVS IPENAPVGT SVTQLHATDADIGENAKIHFSFSNLVSNIARRLFHL V.6 264 NDNHPV'FETEIEVIENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLFHL 323 V.1 303 NATTGLITIKEPLDREETPNHKLLVLASDGGLMPARMVLVNVTDVNDNVPSIDIRYI 362 NATTCLITIKEFLDREETPNHKLLVLAS DGGLMPARAMVINVTDVNDNVPSIDIRYIVN V.6 324 NATTGLITIKEPLDREETPNHKLLVLASDGGLMPA AVLVNVTDVNDNVPSIDIRYIVN 383 WO 2004/098515 PCT/US2004/013568 280 V.1 363 PVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLETAA 422 PVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLE AA V.6 384 PVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLENAA 443 V.1 423 YLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNSPG 482 YLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNSPG V.6 444 YLDYESTKEYAIKLLAADAGKPPLNQSAMLFIK<VKDENDNAPVFTQSFVTVSIPENNSPG 503 V.1 483 IQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTVVKKLDREKEDKYLFTILA 542 IQL KVSA DADSGPNA+INYLLGPDAPPEFSLD RTGMLTVVKKLDREKEDKYLFTILA V.6 504 IQLMKVSATDADSGPNAEINYLLGPDAPPEFSLDRRTGMLTVVKKLDREKEDKYLFTILA 563 V.1 543 KDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYGDN 602 KDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEY FYVPENLPRHGTVGLITVTDPDYGDN V.6 564 KDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYKFYVPENLPRHGTVGLITVTDPDYGDN 623 V.1 603 SAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVTIN 662 SAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVTIN V.6 624 SAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVTIN 683 V.1 663 VVDVNDNKPVFIVPPSNCSYELVLPSTNPGTVVFQVIAVDNDTGMNAEVRYSIVGGNTRD 722 VVDVNDNKPVFIVPP N SYELVLPSTNPGTVVFQVIAVDNDTGMNAEVRYSIVGGNTRD V.6 684 VVDVNDNKPVFIVPPYNYSYELVLPSTNPGTVVFQVIAVDNDTGMNAEVRYSIVGGNTRD 743 V.1 723 LFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSVVIVNLFVNESVTNATLI 782 LFAIDQETGNITTLMEKCDVTDLGLHRVLVKANDLGQPDSLFSVVIVNLFVNESVTNATLI V.6 744 LFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSVVIVNLFVNESVTNATLI 803 V.1 783 NELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVVVVIFITAVVRCRQAPHL 842 NELVRKS EAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVVVVIFITAVVRCRQAPHL V.6 804 NELVRKSIEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVVVVIFITAVVRCRQAPHL 863 V.1 843 KAAQKNKQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDGNR 902 KAAQKN QNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDGNR V.6 864 KAAQKNMQNSEWATPNPENRQMIMMKKKKKKKHSPKNLLLNFVTIEETKADDVDSDGNR 923 V.1 903 VTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNSKHHI 962 VTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLN KHHI V.6 924 VTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNLKHHI 983 V.1 963 IQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP 1011 IQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP V.6 984 IQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP 1032 Table LII(f). Nucleotide sequence of transcript variant 109P1 D4 v.7 (SEQ ID NO: 267) ggtggtccag tacctccaaa gatatggaat acactcctga aatatcctga aacctttttt 60 ttttcagaat cctttaataa gcagttatgt caatctgaaa gttgcttact tgtactttat 120 attaatagct attcttgttt ttcttatcca aagaaaaatc ctctaatccc cttttcacat 180 gatagttgtt accatgttta ggcgttagtc acatcaaccc ctctcctctc ccaaacttct 240 cttcttcaaa tcaaacttta ttagtccctc ctttataatg attccttqcc tccttttatc 300 cagatcaatt ttttttcact ttgatgccca gagctgaaga aatggactat tgtataaatt 360 attcattgcc aagagaataa ttgcatttta aacccatgtt ataacaaaga ataatgatta 420 tattttgtga tttgtaacaa atacccttta tfttccctta actattgaat taaatatttt 480 aattatttgt attctcttta actatcttgg tatattaaag tattatcttt tatatatrta 540 tcaatggtgg acacttttat aggtactctg tctcattttt gatactgtag gtatcttatt 600 tcatttatct ttattcttaa tgtacgaatt cataatattt gattcagaac agatttatca 660 ctaattaaca gagtgtcaat tatgctaaca tctcatttac tgattttaat ttaaaacagt 720 ttttgttaac atgcatgttt agggttggct tcttaataat ttcttcttcc tcttctctct 780 ctcctcttct tttggtcagt gttgtgcggg ttaatacaac aaactgtcac aagtgtttgt 840 tgtccgggac gtacattttc gcggtcctgc tagtatgcgt ggtgttccac tctgqcgccc 900 aggagaaaaa ctacaccac cgagaagaaa ttccagaaaa cgtcctgata ggcaacttgt 960 tgaaagacct taacttgtcg ctgattccaa acaagtcctt gacaactact atgcagttca 1020 agctagtgta caagaccgga gatgtgccac tgattcgaat tgaagaggat actggtgaga 1080 tcttcactac cggcgctcgc attgatcgtg agaaattatq tgotqgtatc ccaaqggatg 1140 agcattgctt ttatgaagtg gaggttgcca ttttgccgga tgaaatattt agactggtta 1200 agatacgttt tctgatagaa gatataaatg ataatqcacc attgttccca gcaacagtta 1260 WO 2004/098515 PCT/US2004/013568 281 tcaacatatc aattccagag aactcggcta taaactctaa atatactctc ccagcggctg 1320 ttgatcctga cgtaggcata aacggagttc aaaactacga actaattaag agtcaaaaca 1380 tttttggcct cgatgtcatt gaaacaccag aaggagacaa gatgccacaa ctgattgttc 1440 aaaaggagtt agatagggaa gagaaggata cctatgtgat gaaagtaaag gttgaagatg 1500 gtggctttcc toaaagatcc agtactgcta ttttgcaagt aagtgttact gatacaaatg 1560 acaaccaccc agtctttaag gagacagaga ttgaagtcag tataccagaa aatgctcctg 1620 taggcacttc agtgacacag ctccatgcca cagatgctga cataggtqaa aatgccaaga 1680 tccacttctc tttcagcaat ctagtctcca acattgccag gagattattt cacctcaatg 1740 ccaccactgg acttatcaca atcaaagaac cactggatag ggaagaaaca ccaaaccaca 1800 agttactggt tttggcaagt gatggtggat tgatgccagc aagagcaatg gtgctggtaa 1860 atgttacaga tgtcaatgat aatgtcccat ccattgacat aagatacatc gtcaatcctg 1920 tcaatgacac agttgttctt tcagaaaata ttccactcaa caccaaaatt gctctcataa 1980 ctgtgacgga taaggatgcg gaccataatg gcagggtgac atgcttcaca gatcatgaaa 2040 ttcctttcag attaaggcca gtattcagta atcagttcct cctggagaat gcagcatatc 2100 ttgactatga gtccacaaaa gaatatgcca ttaaattact ggctgcagat gctggcaaac 2160 ctcctttgaa tcagtcagca atgctcttca tcaaagtgaa agatgaaaat gacaatgctc 2220 cagttttcac ccagtctttc gtaactgttt ctattcctga qaataactct cctggcatcc 2280 agttgatgaa agtaagtgca acgqatgcag acagtgggcc taatgctgaq atcaattacc 2340 tgctaggccc tgatgctcca cctgaattca gcctggatcg tcqtacaggc atgctgactg 2400 tagtgaagaa actagataga gaaaaagagg ataaatattt attcacaatt ctggcaaaag 2460 ataatggggt accaccctta accagcaatg tcacagtctt tgtaagcatt attgatcaga 2520 atgacaatag cccagttttc actcacaatg aatacaaatt ctatgtccca gaaaaccttc 2580 caaggcatgg tacagtagga ctaatcactg taactgatcc tgattatgga gacaattctg 2640 cagttacgct ctccatttta gatgacaatg atgacttcac cattgattca caaactggtg 2700 tcatccgacc aaatatttca tttgatagaq aaaaacaaga atcttacact ttctatgtaa 2760 aggctgagga tggtggtaga gtatcacgtt cttcaagtgc caaagtaacc ataaatgtgg 2820 ttgatgtcaa tgacaacaaa ccaqttttca ttgtccctcc ttacaactat tcttatgaat 2880 tggttctacc gtccactaat ccaggcacag tggtctttca ggtaattgct gttgacaatg 2940 acactggcat gaatgcagag gttcgttaca gcattgtagg aggaaacaca agagatctgt 3000 ttgcaatcga ccaagaaaca ggcaacataa cattgatgga gaaatgtgat gttacagacc 3060 ttggtttaca cagagtgttg gtcaaagcta atgacttagg acagcctgat tctctcttca 3120 gtgttgtaat tgtcaatctg ttcgtgaatg agtcagtgac caatgctaca ctgattaatg 3180 aactggtgcg caaaagcatt gaagcaccag tgaccccaaa tactgagata gctgatgtat 3240 cctcaccaac tagtgactat gtcaagatcc tqgttgcagc tgttgctggc accataactg 3300 tcgttgtagt tattttcatc actgctgtag taagatgtcg ccaggcacca caccttaagg 3360 ctgctcagaa aaacatgcag aattctgaat gggctacccc aaacccagaa aacaggcaga 3420 tgataatgat gaagaaaaag aaaaagaaga agaagcattc ccctaacaac ctgctgctta 3480 atgttgtcac tattgaagaa actaaggcag atgatgttga cagtgatgca aacagagtca 3540 cactagacct tcctattgat ctagaagagc aaacaatggg aaagtacaat tgggtaacta 3600 cacctactac tttcaagcct qacagccctq atttggcccg acactacaaa tctgcctctc 3660 cacagcctgc cttccaaatt caqcctgaaa ctcccctgaa tttgaagcac cacatcatcc 3720 aagaactgcc tctcgataac acctttgtgg cctgtgactc tatctccaat tgttcctcaa 3780 gcagttcaga tccctacagc gtttctgact gtggctatcc agtgacaacc ttcgaggtac 3840 ctgtgtccgt acacaccaga ccgactgatt ccaggacatg aactattgaa atctgcagtg 3900 agatgtaact ttctaggaac aacaaaattc cattcccctt ccaaaaaatt tcaatgattg 3960 tgatttcaaa attaggctaa gatcattaat tttgtaatct agatttccca ttataaaagc 4020 aagcaaaaat catcttaaaa atgatgtcct agtgaacctt gtgctttctt tagctgtaat 4080 ctggcaatgg aaatttaaaa tttatggaag agacagtgca gcgcaataac agagtactct 4140 catgctgttt ctctgtttgc tctgaatcaa cagccatgat gtaatataag gctgtcttgq 4200 tgtatacact tatggttaat atatcagtca tgaaacatgc aattacttgc cctgtctgat 4260 tgttgaataa ttaaaacatt atctccagga gtttggaagt gagctgaact agccaaacta 4320 ctctctgaaa ggtatccagg gcaagagaca attttaagac cccaaacaaa caaaaaacaa 4380 aaccaaaaca ctctggttca gtgatttgaa aatattgact aacataatat tgctgagaaa 4440 atcattttta ttacccacca ctctgcttaa aagttgagtg ggccgggcgc ggtggctcac 4500 gcctgtaatt ccagcacttt gggaggccga ggcgggtgga tcacgaggtc aggatattga 4560 gaccatcctg gctaacatgg tgaaacccca tctccactaa aaaacaaaa aattagctqg 4620 gcgtggtggc gggcgcctgt agtcccagct actcgggagg ctgaggcagg agaatggcgt 4680 gaacccggga ggcggagctt gcagtgagcc gagatggcgc cactgcactc cagctgggt 4740 gacagagcaa gactctgtct caaaaagaaa aaaatgttca gtgatagaaa ataattttac 4800 taggttttta tgttgattgt actcatgctg ttccactcct tttaattatt aaaaagttat 4860 ttttggctgg gtgtggtggc tcatacctgt aatcccagca ctttgggagg ccgaggcggg 4920 tggatcacct gaggtcagga gttcaagacc agtctggcca acat 4964 WO 2004/098515 PCT/US2004/013568 282 Table LIll(f). Nucleotide sequence alignment of 109P1D4 v.1 (SEQ ID NO: 268) and 109P1D4 v.7 (SEQ ID NO: 269) Score 5664 bits (2946), Expect = 0.01dentities = 3000/3027 (99%) Strand = Plus / Plus V.1 852 ttgttgtccgggacgtacattttcgcggtcctgctagcatgcgtggtgttccactctggc 911 |11|I1 i IIIII11 III111|II 1iII I II I IiIi lii II iii II 11I I I I |I I V.7 837 ttgttgtccgggacgtacattttcgcggtcctgctagtatgcgtggtgttccactctggc 896 V.1 912 gcccaggagaaaaactacaccatccgagaagaaatgccagaaaacgtcctgataggcgac 971 II |IIIIIIIIl|III II |||1 1 I1l11 I I111 i i iI I I I I l I i|I I I I i II i V.7 897 gcccaggagaaaaactacaccatccgagaagaaattccagaaaacgtcctgataggcaac 956 V.1 972 ttgttgaaagaccttaacttgtcgctgattccaaacaagtccttgacaactgctatgcag 1031 I I | IIIII I||I| I| |III I 1111I I I I 11 11 11 i i I I| II lii i IIi I II 11 I V.7 957 ttgttgaaagaccttaacttgtcgctgattccaaacaagtccttgacaactactatgcag 1016 V.1 1032 ttcaagctagtgtacaagaccggagatgtgccactgattcgaattgaagaggatactggt 1091 II lI I i IiII li i l i II |I IiIII |II |Ii I Ilil i 1 I I 1 i | II II I I 1 I I II | I | |I I I [ I I I V.7 1017 ttcaagctagtgtacaagaccggagatgtgccactgattcgaattgaagaggatactggt 1076 V.1 1092 gagatcttcactactggcgctcgcattgatcgtgagaaattatgtgctggtatcccaagg 1151 I l I l i ii i i I 1| li 1111 || I I i l 1 1 I Ii iI | II I Ii II IlII V.7 1072 gagatcttcactaccggcgctcgcattgatcgtgagaaattatgtgctggtatcccaagg 1136 V.1 1152 gatgagcattgcttttatgaagtggaggttgccattttgccggatgaaatatttagactg 1211 II|II iiiIIIlIIiIIli|IIIi il II I 1 I 11 1 11 1 1 1 11 1 l ii 111| II 1 I1 IlI I I I I Il V.7 1137 gatgagcattgcttttatgaagtggaggttgccattttgccggatgaaatatttagactg 1196 V.1 1212 gttaagatacgttttctgatagaagatataaatgataatgcaccattgttcccagcaaca 1271 II| II II IIIi|lIIII IIII JIilli I I l11I 1 1 1111 || ill | 11 1 1 I i i I I I i I V.7 1197 gttaagatacgttttctgatagaagatataaatgataatgcaccattgttcccagcaaca 1256 V.1 1272 gttatcaacatatcaattccagagaactcggctataaactctaaatatactctcccagcg 1331 V.7 1257 gttatcaacatatcaattccagagaactcggctataaactctaaatatactctcccagcg 1316 V.1 1332 gctgttgatcctgacgtaggaataaacggagttcaaaactacgaactaattaagagtcaa 1391 1111II1 iiI I ||111 1 || I lIi J I |il l I I|| I 1 I I Jil II 11111 1 l I I V.7 1317 gctgttgatcctgacgtaggcataaacggagttcaaaactacgaactaattaagagtcaa 1376 V.1 1392 aacatttttggcctcgatgtcattgaaacaccagaaggagacaagatgccacaactgatt 1451 V.7 1377 aacatttttgcctcgatgtcattgaaacaccagaaggagacaagatgccacaactgatt 1436 V.1 1452 gttcaaaaggagttagatagggaagagaaggatacctacgtgatgaaagtaaaggttgaa 1511 II I|IIIIIIIII IIl I I iI I I | l I I I l I I I i| I I l | I I I 1 1 1 1 1 1 | I |I V.7 1437 gttcaaaaggagttagatagggaagagaaggatacctatgtgatgaaagtaaaggttgaa 1496 V.1 1512 gatggtggctttcctcaaagatccagtactgctattttgcaagtgagtgttactgataca 1571 V.7 1497 gatggtggctttcctcaaagatccagtactgctattttgcaagtaagtgttactgataca 1556 V.1 1572 aatgacaaccacccagtetttaaggagacagagattgaagtcagtataccagaaaatgct 1631 V.7 :1557 aatgacaaccacccagtctttaaggagacagagattgaagtcagtataccagaaaatgct 1616 WO 2004/098515 PCT/US2004/013568 283 v.1 1632 cctgtaggcacttcagtgacacagctccatgccacagatgctgacataggtgaaaatgcc 1691 l ll I I II 111ii I 111 lIl i IIIl IlI i i III II 1i I11 111 1 i11i i Ii|I V.7 1617 cctgtaggcacttcagtgacacagctccatgccacagatgctgacataggtgaaaatgcc 1676 V.1 1692 aagatccacttctctttcagcaatctagtctccaacattgccaggagattatttcacctc 1751 11111 IllIIIIl IIlIIIII ii IiI II l I II 11 11I1 1 1I1 i111I| I|111 11 111 V.7 1677 aagatccacttctctttcagcaatctagtctccaacattgccaggagattatttcacctc 1736 V.1 1752 aatgccaccactggacttatcacaatcaaagaaccactggatagggaagaaacaccaaac 1811 l I I I I | I I I l i l I I I l I I l I I I I l I I I I I iI I I i 1I I I I I l V.7 1737 aatgccaccactggacttatcacaatcaaagaaccactggatagggaagaaacaccaaac 1796 V.1 1812 cacaagttactggttttggcaagtgatggtggattgatgccagcaagagcaatggtgctg 1871 V.7 1797 cacaagttactggttttggcaagtgatggtggattgatgccagcaagagcaatggtgctg 1856 V.1 1872 gtaaatgttacagatgtcaatgataatgtcccatccattgacataagatacatcgtcaat 1931 l l 1111i111 1I11111l1I111111I I IlIIiI | |IiIIII 11111I11I I|I ] 1111 V.7 1857 gtaaatgttacagatgtcaatgataatgtcccatccattgacataagatacatcgtcaat 1916 V.1 1932 cctgtcaatgacacagttgttctttcagaaaatattccactcaacaccaaaattgctctc 1991 11111l 11 1 1 1 1 1 1 1 IlI Il l IIIiI I | l 11111 II II I|l II 11 |1 Ii II V.7 1917 cctgtcaatgacacagttgttctttcagaaaatattccactcaacaccaaaattgctctc 1976 V.1 1992 ataactgtgacggataaggatgcggaccataatggcagggtgacatgcttcacagatcat 2051 V.7 1977 ataactgtgacggataaggatgcggaccataatggcagggtgacatgcttcacagatcat 2036 V.1 2052 gaaatccctttcagattaaggccagtattcagtaatcagttcctcctggagactgcagca 2111 iii l l1I I lI l ll l i IIIlIIi l 1 1 11 1 11 1 1 |11 1 1 1 I I I I||1 I 1 I II1I1 V.7 2037 gaaattcctttcagattaaggccagtattcagtaatcagttcctcctggagaatgcagca 2096 V.1 2112 tatcttgactatgagtccacaaaagaatatgccattaaattactggctgcagatgctggc 2171 V.7 2097 tatcttgactatgagtccacaaaagaatatgccattaaattactggctgcagatgctggc 2156 V.1 2172 aaacctcctttgaatcagtcagcaatgctcttcatcaaagtgaaagatgaaaatgacaat 2231 V.7 2157 aaacctcctttgaatcagtcagcaatgctcttcatcaaagtgaaagatgaaaatgacaat 2216 V.1 2232 gctccagttttcacccagtctttcgtaactgtttctattcctgagaataactctcctggc 2291 V.7 2217 gctccagttttcacccagtctttcgtaactgtttctattcctgagaataactctcctggc 2276 V.1 2292 atccagttgacgaaagtaagtgcaatggatgcagacagtgggcctaatgctaagatcaat 2351 V.7 2277 atccagttgatgaaagtaagtgcaacggatgcagacagtgggcctaatgctgagatcaat 2336 V.1 2352 tacctgctaggccctgatgctccacctgaattcagcctggattgtcgtacaggcatgctg 2411 Il I I i il I I 11||11 1 I|I I i I I I I 11 l Ii | I I I || | |I | I II I I V.7 2337 tacctgctaggccctgatgctccacctgaattcagcctggatcgtcgtacaggcatgctg 2396 V.1 2412 actgtagtgaagaaactagatagagaaaaagaggataaatatttattcacaattctggca 2471 V.7 2397 actgtagtgaagaaactagatagagaaaaagaggataaatatttattcacaattctggca 2456 WO 2004/098515 PCT/US2004/013568 284 V.1 2472 aaagataacggggtaccacccttaaccagcaatgtcacagtctttgtaagcattattgat 2531 lII ll ll i I II I|I11 1 1 1 1lilil1 I Il l li l 111ll 111I l 1 1 1I11l1 V.7 2457 aaagataatggggtaccacccttaaccagcaatgtcacagtctttgtaagcattattgat 2516 V.1 2532 cagaatgacaatagcccagttttcactcacaatgaatacaacttctatgtcccagaaaac 2591 V.7 2517 cagaatgacaatagcccagttttcactcacaatgaatacaaattctatgtcccagaaaac 2576 V.1 2592 cttccaaggcatggtacagtaggactaatcactgtaactgatcctgattatggagacaat 2651 1 i l ll lIIlIIi l iIl Ii I11 1 1 1 l ll 1 1 11111i 1|| I lil l l ili V.7 2577 cttccaaggcatggtacagtaggactaatcactgtaactgatcctgattatggagacaat 2636 V.1 2652 tctgcagttacgctctccattttagatgagaatgatgacttcaccattgattcacaaact 2711 il Ii 11l1il 1 Il ll1 1 II l lill 11111l1il 1l1I |1l11I 1l1lI1I11l11l1 V.7 2637 tctgcagttacgctctccattttagatgagaatgatgacttcaccattgattcacaaact 2696 V.1 2712 ggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatcttacactttctat 2771 [1l1il 1llI 1 I 11 I II11 II Il1 I ll |I l liII II I I I||111 ||Iii V.7 2697 ggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatcttacactttctat 2756 V.1 2772 gtaaaggctgaggatggtggtagagtatcacgttcttcaagtgccaaagtaaccataaat 2831 I l l I l1l 1l lll1I11 Il 1 II1 I I1 I II 11111 III | l i I I I II I11 I I V.7 2757 gtaaaggctgaggatggtggtagagtatcacgttcttcaagtgccaaagtaaccataaat 2816 V.1 2832 gtggttgatgtcaatgacaacaaaccagttttcattgtccctccttccaactgttcttat 2891 I i lIl lIII I l liI i I l1 1 1 I i lI | I 1 11 |I1 I I 11l ii V.7 2817 gtggttgatgtcaatgacaacaaaccagttttcattgtccctccttacaactattcttat 2876 V.1 2892 gaattggttctaccgtccactaatccaggcacagtggtctttcaggtaattgctgttgac 2951 IiI l 1l lIll I I IlIIIIl i II 11l I ll111 Iil I 11 1l II I 1 lili I 1I|| V.7 2877 gaattggttctaccgtccactaatccaggcacagtggtctttcaggtaattgctgttgac 2936 V.1 2952 aatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaaacacaagagat 3011 V.7 2937 aatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaaacacaagagat 2996 V.1 3012 ctgtttgcaatcgaccaagaaacaggcaacataacattgatggagaaatgtgatgttaca 3071 V.7 2997 ctgtttgcaatcgaccaagaaacaggcaacataacattgatggagaaatgtgatgttaca 3056 V.1 3072 gaccttggtttacacagagtgttggtcaaagctaatgacttaggacagcctgattctctc 3131 V.7 3057 gaccttggtttacacagagtgttggtcaaagctaatgacttaggacagcctgattctctc 3116 V.1 3132 ttcagtgttgtaattgtcaatctgttcgtgaatgagtcggtgaccaatgctacactgatt 3191 V.7 3117 ttcagtgttgtaattgtcaatctgttcgtgaatgagtcagtgaccaatgctacactgatt 3176 V.1 3192 aatgaactggtgcgcaaaagcactgaagcaccagtgaccccaaatactgagatagctgat 3251 lililili I ill Il Ill Il iI IlIII lIIl I | Il l lI | II 11 1 11l I11 1 11 1 1 11 1 1 II I V.7 3177 aatgaactggtgcgcaaaagcattgaagcaccagtgaccccaaatactgagatagctgat 3236 V.1 3252 gtatcctcaccaactagtgactatgtcaagatcctggttgcagctgttgctggcaccata 3311 V.7 3237 gtatcctcaccaactagtgactatgtcaagatcctggttgcagctgttgctggcaccata 3296 WO 2004/098515 PCT/US2004/013568 285 V.1 3312 actgtcgttgtagttattttcatcactgctgtagtaagatgtcgccaggcaccacacctt 3371 11I1I11111I1I 111 Ii l l ii i I I I I I |I iil | | II | |1 I|I1 1 1 1 1 1 1 1 1 Ii i I V.7 3297 actgtcgttgtagttattttcatcactgctgtagtaagatgtcgccaggcaccacacctt 3356 V.1 3372 aaggctgctcagaaaaacaagcagaattctgaatgggctaccccaaacccagaaaacagg 3431 I i i iIi llI l lIII IIII lIII I 11 1 1 I1 I1I1 i1 I1I i1 II iII l i i V.7 3357 aaggctgctcagaaaaacatgcagaattctgaatgggctaccccaaacccagaaaacagg 3416 V.1 3432 cagatgataatgatgaagaaaaagaaaaagaagaagaagcattcccctaagaacttgctg 3491 V.7 3417 cagatgataatgatgaagaaaaagaaaaagaagaagaagcattcccctaagaacctgctg 3476 V.1 3492 cttaattttgtcactattgaagaaactaaggcagatgatgttgacagtgatggaaacaga 3551 H11 III I1 I I I I I i I 1 1 I I| 1 iii II V.7 3477 cttaatgttgtcactattgaagaaactaaggcagatgatgttgacagtgatggaaacaga 3536 V.1 3552 gtcacactagaccttcctattgatctagaagagcaaacaatgggaaagtacaattgggta 3611 i I 111I l i i i Ii i li i iIi ii ii i i i iIIlIiii iii lii1ii1 11 1 11 1 11 1 11 1 11 1 1 V.7 3537 gtcacactagaccttcctattgatctagaagagcaaacaatgggaaagtacaattgggta 3596 V.1 3612 actacacctactactttcaagcccgacagccctgatttggcccgacactacaaatctgcc 3671 V.7 3597 actacacctactactttcaagcctgacagccctgatttggccogacactacaaatctgcc 3656 V.1 3672 tctccacagcctgccttccaaattcagcctgaaactcccctgaattcgaagcaccacatc 3731 l liI Ill iIi IIii l I 11 11 I I I|II I I 1 11 i I I i I I V.7 3657 tctccacagcctgccttccaaattcagcctgaaactcccctgaatttgaagcaccacatc 3716 V.1 3732 atccaagaactgcctctcgataacacctttgtggcctgtgactctatctccaagtgttcc 3791 l l I iI Il lI lI I I I i I I I I1 I1 || |I1|1 I I lI II II I1 | I1 I I I11 V.7 3717 atccaagaactgcctctcgataacacctttgtggcctgtgactctatctccaattgttcc 3776 V.1 3792 tcaagcagttcagatccctacagcgtttctgactgtggctatccagtgacgaccttcgag 3851 V.7 3777 tcaagcagttcagatccctacagcgtttctgactgtggctatccagtgacaaccttcgag 3836 V.1 3852 gtacctgtgtccgtacacaccagaccg 3878 V.7 3837 gtacctgtgtccgtacacaccagaccg 3863 Score = 1567 bits (815), Expect = 0.OIdentities = 829/836 (99%) Strand = Plus / Plus V.1 3 ggtggtccagtacctccaaagatatggaatacactcctgaaatatcctgaaaactttttt 62 V.7 1 ggtggtccagtacctccaaagatatggaatacactcctgaaatatcctgaaacctttttt 60 V.1 63 ttttcagaatcctttaataagcagttatgtcaatctgaaagttgcttacttgtactttat 122 V.7 61 ttttcagaatcctttaataagcagttatgtcaatctgaaagttgcttacttgtactttat 120 V.1 123 attaatagctattcttgtttttcttatccaaagaaaaatcctctaatccccttttcacat 182 V.7 121 attaatagctattcttgtttttcttatccaaagaaaaatcctctaatccccttttcacat 180 WO 2004/098515 PCT/US2004/013568 286 v.1 183 gatagttgttaccatgtttaggcattagtcacatcaacccctctcctctcccaaacttct 242 v.7 181 gatagttgttaccatgtttaggcgttagtcacatcaacccctctcctctcccaaacttct 240 V.1 243 cttcttcaaatcaaactttattagtccctcctttataatgattccttgcctcgttttatc 302 V.7 241 cttcttcaaatcaaactttattagtccctcctttataatgattccttgcctccttttatc 300 V.1 303 cagatcaattttttttcactttgatgcccagagctgaagaaatggactactgtataaatt 362 lilllilllllillllllllllllillillllilllll1lll1ll1ll1 1111111111 V.7 301 cagatcaattttttttcactttgatgcccagagctgaagaaatggactattgtataaatt 360 V.1 363 attcattgccaagagaataattgcattttaaacccatattataacaaagaataatgatta 422 111i11I111l11l1l11l1l11l11ll111ll1111 1111111Ill11|Ilil11|Il V.7 361 attcattgccaagagaataattgcattttaaacccatgttataacaaagaataatgatta 420 V.1 423 tattttgtgatttgtaacaaataccctttattttcccttaactattgaattaaatatttt 482 V.7 421 tattttgtgatttgtaacaaataccctttattttcccttaactattgaattaaatatttt 480 V.1 483 aattatttgtattctctttaactatcttggtatattaaagtattatcttttatatattta 542 V.7 481 aattatttgtattctctttaactatcttggtatattaaagtattatcttttatatattta 540 V.1 543 tcaatggtggacacttttataggtactctgtgtcatttttgatactgtaggtatcttatt 602 1111|1111111 li11111111|i1111111111111ll llll llllllll V.7 541 tcaatggtggacacttttataggtactctgtgtcatttttgatactgtaggtatcttatt 600 V.1 603 tcatttatctttattcttaatgtacgaattcataatatttgattcagaacaaatttatca 662 I11 1llllI I lill lllllllll 1 llllll i111111111 111ii11111| l1il1 lll V.7 601 tcatttatctttattcttaatgtacgaattcataatatttgattcagaacagatttatca 660 V.1 663 ctaattaacagagtgtcaattatgctaacatctcatttactgattttaatttaaaacagt 722 11 1111111 1l lil i11 11111 1111||1111lil11111111111111 I liI l l V.7 661 ctaattaacagagtgtcaattatgctaacatctcatttactgattttaatttaaaacagt 720 V.1 723 ttttgttaacatgcatgtttagggttggcttcttaataatttcttcttcctcttctctct 782 i 1 1 1 1 1 l i l | 1 l i l l l l l l l l l l l l l l l 1 1 1 1 1 1 1 1 1 1 | 1 1 1 1 1 1 1 li li V.7 721 ttttgttaacatgcatgtttagggttggcttcttaataatttcttcttcctcttctctct 780 V.1 783 ctcctcttcttttggtcagtgttgtgcgggttaatacaacaaactgtaacaagtgt 838 li l l l l l l lllilllllll l i 1 1 11 1 11 1 lllllll lilllllll 111111 || V.7 781 ctcctcttcttttggtcagtgttgtgcgggttaatacaacaaactgtcacaagtgt 836 Table LIV(f). Peptide sequences of protein coded by 109P1D4 v.7 (SEQ ID NO: 270) MFRVGFLIIS SSSSLSPLLL VSVVRVNTTN CHKCLLSGTY IFAVLLVCVV FHSGAQEKNY 60 TIREEIPENV LIGNLLKDLN LSLIPNKSLT TTMQFKLVYK TGDVPLIRIE EDTGETFTTG 120 ARIDREKLCA GIPRDEHCFY EVEVAILPDE IFRLVKIRFL IEDINDNAPL FPATVINISI 180 PENSAINSKY TLPAAVDPDV GINGVQNYEL IKSQNIFGLD VIETPEGDKM PQLIVQKELD 240 REEKDTYVMK VKVEDGGFPQ RSSTAILQVS VTDTNDNHPV FKETEIEVSI PENAPVGTSV 300 TQLHATDADI GENAKIHFSF SNLVSNIARR LFHLNATTGL ITIKEPLDRE ETPNHKLLVL 360 ASDGGLMPAR AMVLVNVTDV NDNVPSIDIR YIVNPVNDTV VLSENIPLNT KIALITVTDK 420 DADHNGRVTC FTDHEIPFRL RPVFSNQFLL ENAAYLDYES TKEYAIKLLA ADAGKPPLNQ 480 SAMLFIKVKD ENDNAPVFTQ SFVTVSIPEN NSPGIQLMKV SATDADSGPN AEINYLLGPD 540 APPEFSLDRR TGMLTVVKKL DREKEDKYLF TILAKDNGVP PLTSNVTVFV SIIDQNDNSP 600 VFTHNEYKFY VPENLPRHGT VGLITVTDPD YGDNSAVTLS ILDENDDFTI DSQTGVIRPN 660 WO 2004/098515 PCT/US2004/013568 287 ISFDREKQES YTFYVKAEDG GRVSRSSSAK VTINVVDVND NKPVFIVPPY NYSYELVLPS 720 TNPGTVVFQV IAVDNDTGMN AEVRYSIVGG NTRDLFAIDQ ETGNITLMEK CDVTDLGLHR 780 VLVKANDLGQ PDSLFSVVIV NLFVNESVTN ATLINELVRK SIEAPVTPNT EIADVSSPTS 840 DYVKILVAAV AGTITVVVVI FITAVVRCRQ APHLKAAQKN MQNSEWATPN PENRQMIMMK 900 KKKKKKKHSP KNLLLNVVTI EETKADDVDS DGNRVTLDLP IDLEEQTMGK YNWVTTPTTF 960 KPDSPDLARH YKSASPQPAF QIQPETPLNL KHHIIQELPL DNTFVACDSI SNCSSSSSDP 1020 YSVSDCGYPV TTFEVPVSVH TRPTDSRT 1048 Table LV(f). Amino acid sequence alignment oi 109P104 v.1 (SEQ ID NO: 271) and 109P D4 V. (SEQ ID NO: 272) Score 1961 bits (5081), Expect = 0.01dentities = 992/1009 (98%), Positives = 995/1009 (98%) V.1 3 LLSGTYIFAVLLACVVFHSGAQEKNYTIREEMPENVLIGDLLKDLNLSLIPNKSLTTAMQ 62 LLSGTYIFAVLL CVVFHSGAQEKNYTIREE+PENVLIG+LLKDLNLSLIPNKSLTT MQ V.7 35 LLSGTYIFAVLLVCVVFHSGAQEKNYTIREEIPENVLIGNLLKDLNLSLIPNKSLTTTMQ 94 V.1 63 FKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIFRL 122 FKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIFRL V.7 95 FKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIFRL 154 V.1 123 VKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIKSQ 182 VKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIKSQ V.7 155 VKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIKSQ 214 V.1 183 NIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVTDT 242 NIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVTDT V.7 215 NIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVTDT 274 V.1 243 NDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLFHL 302 NDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLFHL V.7 275 NDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLFHL 334 V.1 303 NATTGLITIKEPLDREETPNHKLLVLASDGGLMPAPAMVLVNVTDVNDNVPSIDIRYIVN 362 NATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYIVN V.7 335 NATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYIVN 394 V.1 363 PVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLETAA 422 PVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLE AA V.7: 395 PVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLENAA 454 V.1 423 YLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNSPG 482 YLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNSPG V.7 455 YL

D

YESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNSPG 514 V.1 483 IQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTVVKKLDREKEDKYLFTILA 542 IQL KVSA DADSGPNA+INYLLGPDAPPEFSLD RTGMLTVVKKLDREKEDKYLFTILA V.7 515 IQLMKVSATDADSGPNAEINYLLGPDAPPEFSLDRRTGMLTVVKKLDREKEDKYLFTILA 574 V.1 543 KDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYGDN 602 KDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEY FYVPENLPRHGTVGLITVTDPDYGDN V.7 575 KDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYKFYVPENLPRHGTVGLITVTDPDYGDN 634 V.1 603 SAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVTIN 662 SAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVTIN V.7 635 SAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVTIN 694 V.1 663 VVDVNDNKPVFIVPPSNCSYELVLPSTNPGTVVFQVIAVDNDTGMNAEVRYSIVGGNTRD 722 VVDVNDNKPVFIVPP N SYELVLPSTNPGTVVFQVIAVDNDTGMNAEVRYSIVGGNTRD V.7 695 VVDVNDNKPVFIVPPYNYSYELVLPSTNPGTVVFQVIAVDNDTGMNAEVRYSIVGGNTRD 754 V.1 723 LFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSVVIVNLFVNESVTNATLI 782 LFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSVVIVNLFVNESVTNATLI V.7 755 LFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSVVIVNLFVNESVTNATLI 814 V.1 783 NELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVVVVIFITAVVRCRQAPHL 842 NELVRKS EAFVTPNTEIADVSSPTSDYVKILVAAVAGTITVVVVIFITAVVRCRQAPHL V.7 815 NELVRKSIEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVVVVIFITAVVRCRQAPHL 874 V.1 843 KAAQKNKQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDGNR 902 WO 2004/098515 PCT/US2004/013568 288 KAAQKN QNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLN VTIEETKADDVDSDGNR V.7 875 KAAQKNMQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNVVTIEETKADDVDSDGNR 934 V.1 903 VTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNSKHHI 962 VTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLN KHHI V.7 935 VTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNLKHHI 994 V.1 963 IQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP 1011 IQELPLDNTFVACDSIS CSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP V.7 995 IQELPLDNTFVACDSISNCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP 1043 Table LII(g). Nucleotide sequence of transcript variant 109Pi D4 v.8 (SEQ ID NO: 273) ggtggtccag tacctccaaa gatatggaat acactcctga aatatcctga aacctttttt 60 ttttcagaat cctttaataa gcagttatgt caatctgaaa gttgcttact tgtactttat 120 attaatagct attcttgttt ttcttatcca aagaaaaatc ctctaatccc cttttcacat 180 gatagttgtt accatgttta ggcgttagtc acatcaaccc ctctcctctc ccaaacttct 240 cttcttcaaa tcaaacttta ttagtccctc ctttataatg attccttgcc tccttttatc 300 cagatcaatt ttttttcact ttgatgccca gagctgaaga aatggactat tgtataaatt 360 attcattgcc aagagaataa ttgcatttta aacccatgtt ataacaaaga ataatgatta 420 tattttgtga tttgtaacaa atacccttta ttttccctta actattgaat taaatatttt 480 aattatttgt attctcttta actatcttgg tatattaaag tattatctt tatatattta 540 tcaatggtgg acacttttat aggtactctg tgtcattttt gatactgtag gtatcttatt 600 tcatttatct ttattcttaa tgtacgaatt cataatattt gattcagaac agatttatca 660 ctaattaaca gagtgtcaat tatgctaaca tctcatttac tgattttaat ttaaaacagt 720 ttttgttaac atgcatgttt agggttggct tcttaataat ttcttcttcc tcttctctct 780 ctcctcttct tttggtcagt gttgtgcggg ttaatacaac aaactgtcac aagtgtttgt 840 tgtccgggac gtacattttc gcggtcctgc tagtatgcqt qgtgttccac tctggcgccc 900 aggagaaaaa ctacaccatc cgagaagaaa ttccagaaaa cgtcctcata ggcaacttgt 960 tgaaagacct taacttgtcg ctgattccaa acaagtcctt gacaactact atgcagttca 1020 agctagtgta caagaccgga gatgtgccac tgattcgaat tgaagaggat actggtgaga 1080 tcttcactac cggcgctcgc attgatcgtg agaaattatg tgctggtatc ccaagggatg 1140 agcattgctt ttatgaagtg gaggttgcca ttttgccgga tgaaatattt agactggtta 1200 agatacgttt tctgatagaa gatataaatg ataatgcacc attgttccca gcaacagtta 1260 tcaacatatc aattccagag aactcggcta taaactctaa atatactctc ccagcggctq 1320 ttgatcctga cqtaggcata aacggagttc aaaactacga actaattaag agtcaaaaca 1380 tttttggcct cgatgtcatt gaaacaccag aaggagacaa gatgccacaa ctgattgttc 1440 aaaaggagtt agatagggaa gagaaggata cctatgtgat gaaagtaaag gttgaagatg 1500 gtggctttcc tcaaagatcc agtactgcta ttttgcaagt aagtgttact gatacaaatc 1560 acaaccaccc agtctttaag gagacagaga ttgaagtcag tataccagaa aatgctcct 1620 taggcacttc agtgacacag ctccatgcca cagatgctga cataggtgaa aatgccaaga 1680 tccacttctc tttcagcaat ctagtctcca acattgccag gagattattt cacctcaatg 1740 ccaccactgg acttatcaca atcaaagaac cactggatag ggaagaaaca ccaaaccaca 1800 agttactggt tttggcaagt gatggtggat tgatgccagc aagagcaatg gtgctggtaa 1860 atgttacaga tqtcaatgat aatgtcccat ccattgacat aagatacatc gtcaatcctg 1920 tcaatgacac agttgttctt tcagaaaata ttccactcaa caccaaaatt gctctcataa 1980 ctgtgacgga taaggatgcg gaccataatg gcagggtgac atgcttcaca gatcatgaaa 2040 ttcctttcag attaaggcca gtattcagta atcagttcct cctggagaat gcagcatatc 2100 ttgactatga gtccacaaaa gaatatgcca ttaaattact ggctgcagat gctggcaaac 2160 ctcctttgaa tcagtcagca atgctcttca tcaaagtgaa agatgaaaat gacaatgctc 2220 cagttttcac ccagtctttc gtaactgttt ctattcctga qaataactct cctggcatcc 2280 agttgatgaa agtaagtgca acggatgcag acagtgggcc taatgctgaj atcaattacc 2340 tgctaggccc tgatgctcca cctgaattca gcctggatcg tcgtacaggc atactgactg 2400 tagtgaagaa actagataqa gaaaaagagg ataaatattt attcacaatt ctggcaaaag 2460 ataatggggt accaccctta accagcaatg tcacagtctt tqtaagcatt attgatcaga 2520 atgacaatag cccagttttc actcacaatg aatacaaatt ctatgtccca gaaaaccttc 2580 caaggcatgg tacagtagga ctaatcactg taactgatcc tgattatgga gacaattctg 2640 cagttacgct ctccatttta gatgagaatg atgacttcac cattgattca caaactggtg 2700 tcatccgacc aaatatttca tttgatagag aaaaacaaga atcttacact ttctatgtaa 2760 aggctgagga tggtggtaga gtatcacgtt cttcaagtgc caaagtaacc ataaatgtgg 2820 ttgatgtcaa tgacaacaaa ccagttttca ttgtccctcc ttacaactat tcttatgaat 2880 tggttctacc gtccactaat ccaggcacat tggtctttca ggtaattgct gttgacaatg 2940 acactggcat gaatgcagag gttcgttaca gcattgtagg aggaaacaea agagatctgt 3000 WO 2004/098515 PCT/US2004/013568 289 ttgcaatcga ccaagaaaca ggcaacataa cattgatgga gaaatgtqat gttacagacc 3060 ttggtttaca cagagtgttg gtcaaagcta atgacttagg acagcctgat tctctcttca 3120 gtgttgtaat tgtcaatctg ttcgtgaatg agtcagtgac caatgctaca ctgattaatg 3180 aactggtgcg caaaagcatt gaagcaccag tgaccccaaa tactgagata gctgatgtat 3240 cctcaccaac tagtgactat gtcaagatcc tggttgcagc tgttgctggc accataactg 3300 tcgttgtagt tattttcatc actgctgtag taagatgtcg ccaggcacca caccttaagg 3360 ctgctcagaa aaacatgcag aattctcaat gggctacccc aaacccagaa aacaggcaga 3420 tgataatgat gaagaaaaag aaaaagaaga agaagcattc ccctaagaac ctgctgctta 3480 atgttgtcac tattgaagaa actaaggcag atgatgttga cagtgatgga aacagagtca 3540 cactagacct tcctattgat ctagaagagc aaacaatggg aaagtacaat tgggtaacta 3600 cacctactac tttcaagcct gacagccctq atttggcccg acactacaaa tctgcctctc 3660 cacagcctgc cttccaaatt cagcctgaaa ctcccctgaa tttgaagcac cacatcatcc 3720 aagaactgcc tctcgataac acctttgtgg cctgtcactc tatctccaat tgttcctcaa 3780 gcagttcaga tccctacagc gtttctgact gtggctatcc agtgacaacc ttcgaggtac 3840 ctgtgtccgt acacaccaga ccgtcccagc ggcgtgtcac atttcacctg ccagaaggct 3900 ctcaggaaag cagcagtgat ggtggactgg gagaccatga tgcaggcagc cttaccagca 3960 catcccatgg cctgcccctt ggctatcctc aggaggagta ctttgatcgt gctacaccca 4020 gcaatcgcac tgaaggggat ggcaactccg atcctgaatc tactttcata cctgcactaa 4080 agaaagaaat aactgttcaa ccaactgtgg aagaggcctc tgacaactgc actcaagaat 4140 gtctcatcta tggccattct gatgcctgct ggatgccggc atctctggat cattccagct 4200 cttcacaagc acaggcctct gctctatgcc acagcccacc actgtcacag qcctctactc 4260 agcaccacag cccaccagtg acacagacca ttgttctctg ccacagccct ccagtgacac 4320 agaccatcgc attgtgccac agcccaccac cgatacaggt gtctgctctc caccacagtc 4380 ctcctctagt gcagggtact gcacttcacc acagcccacc atcagcacag gcctcagccc 4440 tctgctacag ccctccttta gcacaggctg ctgcaatcag ccacagctct tctctgccac 4500 aggttattgc cctccatcgt agtcaggccc aatcatcagt cagtttgcag caaggttggg 4560 tgcaaggtgc taatggacta tgctctgttg atcagggagt gcaaggtagt gcaacatctc 4620 agttttacac catgtctgaa agacttcatc ccaqtgatga ttcaattaaa gtcattcctt 4680 tgacaacctt cgctccacgc caacaggcca gaccgtccag aggtgattcc cccattatgg 4740 aaacacatcc cttgtaaagc taaaatagtt acttcaaatt ttcagaaaag atgtatatag 4800 tcaaaattta agatacaatt ccaatgagta ttctgattat cagatttgta aataactatg 4860 taaatagaaa cagataccag aataaatcta cagctagacc cttagtcaat agttaaccaa 4920 aaaattgcaa tttgtttaat tcagaatgtg tatttaaaaa gaaaaggaat ttaacaattt 4980 gcatcccctt gtacagtaag gcttatcatg acagagcgta ctatttctga tgtacagtat 5040 tttttgttgt ttttatcatc atgtgcaata ttactgattt gtttccatgc tgattgtgtg 5100 gaaccagtat gtagcaaatg gaaagcctag aaatatctta ttttctaagt ttacctttag 5160 tttacctaaa cttttgttca gataatgtta aaaggtatac gtactctagc cttttttggg 5220 gctttctttt tgatttttgt ttgtggtttt cagttttttt gttgttgtta gtgagtctcc 5280 cttcaaaata cacagtaggt agtgtaaata ctgcttgttt gtgtctctct cctgtcatgt 5340 tttctacctt attccaatac tatattgttg ataaaatttg tatatacatt ttcaataaag 5400 aatatgtata aactgtacag atctagatct acaacctatt tctctactct ttagtagagt 5460 tcgagacaca gaagtgcaat aactgcccta attaagcaac tatttgttaa aaagggcccc 5520 tttttacttt aatagtttag tgtaaagtac atcagaaata aaactgtatc tgacatttta 5580 agcctgtagt ccattattac ttgggtcttt acttctggga atttgtatgt aacagcctag 5640 aaaattaaaa ggaggtggat gcatccaaag cacgagtcac ttaaaatatc gacggtaaac 5700 tactattttg tagagaaact caggaagatt taaatgttga tttgacagct caataggctg 5760 ttaccaaagg gtgttcagta aaaataacaa atacatgtaa ctgtagataa aaccacatac 5820 taaatctata agactaaggg atttttgtta ttctagctca acttactgaa gaaaaccact 5880 aataacaaca agaatatcag gaaggaactt ttcaagaaat gtaattataa atctacatca 5940 aacagaattt taaggaaaaa tgcagaggga gaaataaggc acatgactgc ttcttgcagt 6000 caagaagaaa taccaataac acacacagaa caaaaaccat caaaatctca tatatgaaat 6060 aaaatatatt cttctaagca aagaaacagt actattcata gaaaacatta gttttctcct 6120 gttgtctgtt atttccttct tttatcctct taactqccca ttatcttgta tgtgcacatt 6180 ttataaatgt acagaaacat caccaacttg attttcttcc atagcaaaac tgagaaaata 6240 ccttgtttca gtataacact aaaccaagag acaattgatg tttaatgggg gcggttgggg 6300 ttggggggga gtcaatatct cctattgatt aacttagaca tagattttgt aatgtataac 6360 ttgatattta atttatgatt aaactgtaat tttgtaacat aaactgtggt aattgcataa 6420 tttcattggt gaggatttcc tttgaatatt gagaaagttt cttttcatgt gcccagcagg 6480 ttaagtagcg ttttcagaat atacattatt cccatccatt gtaaagttcc ttaagtcata 6540 tttgactggg cgtgcagaat aacttcttaa ctattaacta tcagagtttg attaataaaa 6600 ttaattaatt ttttttctcc ttcgtgttgt taatgttcca agggatttgg agcatactgg 6660 ttttccaggt gcatgtgaat cccgaaggac tgatgatatt tgaatgttta ttaaattatt 6720 WO 2004/098515 PCT/US2004/013568 290 atcacacaaa tgtgttgata ttgtggctat tgttgatgtt gaaaattgta aacttgggga 6780 agattaagaa aagaaccaat agtgacaaaa atcagtgctt ccagtagatt ttagaacatt 6840 ctttgcctca aaaaacctgc aaagatgatg tgagattttt tcttgtgttt taattatttt 6900 cacattttct ctctgcaaac ctttagtttt ctgatgatct acacacacac atacacacac 6960 acacacacac acgtgcacac acacacattt aaaggatata aaaagaagag gttgaaagat 7020 tattaaataa cttatcaggc atctcaatgg ttactatcta tgttagtgaa aatcaaatag 7080 gactcaaagt tggatatttg ggatttttct tctgacagta taatttattg agttactagq 7140 gaggttctta aatcctcata tctggaaact tgtgaagttt tgacaccttt cctatagata 7200 taggaatgaa ccaatacgct tttattaccc tttctaactc tgattttata atcagactta 7260 gattgtgttt agaatattaa atgactgggc accctcttct tggtttttac cagagaggct 7320 ttgaatggaa gcaggctgag agtagccaaa gaggcaaggg gtattagccc agttattctc 7380 ccctatgcct tctcttccta agcgtccact aggtctggcc ttggaaatct gttacttcta 7440 cggcttcaga tctgatgata tctttttcat cacattacaa gttatttctt tgactgaata 7500 gacagtggta taggttgaca cagcacacaa gtggctattg tgatgtatga tgtatgtagt 7560 cccacaactg caaaacgtct tactgaagca acaatcgaaa aatggttctg ttttaaaaag 7620 gattttgttt gatttgaaat taaaacttca aactgaatga cttatatgag aataatatgt 7680 tcaatcaaag tagttattct attttgtgtc catattccat tagattgtga ttattaattt 7740 tctagctatg gtattactat atcacacttg tgagtatgta ttcaaatact aagtatctta 7800 tatgctacgt gcatacacat tcttttctta aactttacct gtgttttaac taatattgtg 7860 tcagtgtatt aaaaattagc ttttacatat gatatctaca atgtaataaa tttagagagt 7920 aattttgtgt attcttattt acttaacatt ttacttttaa ttatgtaaat ttggttagaa 7980 aataataata aatggttagt gctattgtqt aatggtagca gttacaaaga gcctctgcct 8040 tcccaaacta atatttatca cacatggtca ttaaatggga aaaaaataga ctaaacaaat 8100 cacaaattgt tcagttctta aaatgtaatt atgtcacaca cacaaaaaaa tccttttcaa 8160 tcctgagaaa attaaaggtg ttttactcac atgqatattt caacattagt tttttttgtt 8220 tgtttctttt tcatggtatt actgaaggtg tgtatactcc ctaatacaca tttatgaaaa 8280 tctacttgtt tagactttta tttataotct tctgatttat attttttatt ataattatta 8340 tttcttatct tcttttatat tttttggaaa ccaaatttat agttagttta ggtaaacttt 8400 ttattatgac cattagaaac tattttgaat gtttccaact ggctcaattg gctgggaaaa 8460 catgggaaca agagaagctg aaatatattt ctgcaagaac ctttctatat tatgtgccaa 8520 ttaccacacc agatcaattt tatgcagagg ccttaaaata ttctttcaca gtagctttct 8580 tacactaacc gtcatgtgct tttagtaaat atgattttta aaagcagttc aagttgacaa 8640 cagcagaaac agtaacaaaa aaatctgctc agaaaaatgt atgtgcacaa ataaaaaaaa 8700 ttaatggcaa ttgtttagtg actgtaagtq atacttttta aagagtaaac tgtgtqaaat 8760 ttatactatc cctgcttaaa atattaagat ttttatgaaa tatgtattta tgtttgtatt 8820 gtgggaagat tcctcctctg tgatatcata cagcatctga aagtgaacag tatcccaaag 8880 cagttccaag catgotttgg aagtaagaag gttgactatt gtatgqccaa ggatggcagt 8940 atgtaatcca gaagcaaact tgtattaatt gttctatttc aggttctgta ttgcatgttt 9000 tcttattaat atatattaat aaaagttatg agaaat 9036 Table 1.1I1(g). Nucleotide sequence alignment of 1 09P1 D4 M. (SEQ ID NO: 274)and 1 09P1 D4 v.8 (SEQ ID NO: 275) Score =5664 bits (2946), Expect = Q.0ldentities = 300013027 (99%) Strand =Plus / Plus V.1 852 ttgttgtccgggacgtacattttcgcggtcctgctagcatgcgtggtgttccactctggc 911 V.8 837 ttgttgtccgggacgtacattttcgcggtcctgctagtatgcgtggtgttccactctggc 896 V.1 912 gcccaggagaaaaactacaccatccgagaagaaatgccagaaaacgtcctgataggcgac 971 V.8 897 gcccaggagaaaaactacaccatccgagaagaaattccagaaaacgtcctgataggcaac 956 V.1 972 ttgttgaaagaccttaacttgtcgctgattccaaacaagtccttgacaactgctatgcag 1031 V.8 957 ttgttgaaagaccttaacttgtcgctgattccaaacaagtccttgacaactactatgcag 1016 V.1 1032 ttcaagctagtgtacaagaccggagatgtgccactgattcgaattgaagaggatactggt 1091 V.8 1017 ttcaagctagtgtacaagaccggagatgtgccatgattcgaattgaagaggatactggt 1076 V.1 1092 gagatcttcactactggcgctcgcattgatcgtgagaaattatgtgctggtatcccaagg 1151 1111111 tctttttcat11 cacattacaaii 111111111111 WO 2004/098515 PCT/US2004/013568 291 v.8 1077 gagatcttcactaccggcgctcgcattgatcgtgagaaattatgtgctggtatcccaagg 1136 V.1 1152 gatgagcattgcttttatgaagtggaggttgccattttgccggatgaaatatttagactg 1211 l 111111 llil 11111 I lil illll Il 11 I II 11 I| I II|I1 II I11 V.8 1137 gatgagcattgcttttatgaagtggaggttgccattttgccggatgaaatatttagactg 1196 V.1 1212 gttaagatacgttttctgatagaagatataaatgataatgcaccattgttcccagcaaca 1271 |l l I 1 I I I I I I 1 l l il l 1 i I III I I I I1 I Ill Ii I I I I l l V.8 1197 gttaagatacgttttctgatagaagatataaatgataatgcaccattgttcccagcaaca 1256 V.1 1272 gttatcaacatatcaattccagagaactcggCtataaactctaaatatactctcccagcg 1331 V.8 1257 gttatcaacatatcaattccagagaactcggctataaactctaaatatactctcccagcg 1316 V.1 1332 gctgttgatcctgacgtaggaataaacggagttcaaaactacgaactaattaagagtcaa 1391 IIIIllIIl l l li I ll l Ill Il l l liIIIIIIIIIIIII 11 1 11 1 1 11 1 1l1 I11 11 I11 1 1 11 1 1 li V.8 1317 gctgttgatcctgacgtaggcataaacggagttcaaaactacgaactaattaagagtcaa 1376 V.1 1392 aacatttttggcctcgatgtcattgaaacaccagaaggagacaagatgccacaactgatt 1451 l l I lIl I I 1 11 1111 1 |Il11 |1 I 11 |I i I |11 |III1 V.8 1377 aacatttttggcctcgatgtcattgaaacaccagaaggagacaagatgccacaactgatt 1436 V.1 1452 gttcaaaaggagttagatagggaagagaaggatacctacgtgatgaaagtaaaggttgaa 1511 lI l I l l II II Il I i I l 111I | II II il i 11 11 1 ll I |li V.8 1437 gttcaaaaggagttagatagggaagagaaggatacctatgtgatgaaagtaaaggttgaa 1496 V.1 1512 gatggtggetttcctcaaagatccagtactgctattttgcaagtgagtgttactgataca 1571 lli lIi I I I 11l lil1lll I 1l 11 1 11 1 1 1 1| lIIIIl | | l|I Il | 1 111|| V.8 1497 gatggtggctttcctcaaagatccagtactgctattttgcaagtaagtgttactgataca 1556 V.1 1572 aatgacaaccacccagtctttaaggagacagagattgaagtcagtataccagaaaatgct 1631 11i |1 || I1 lI1 1 I I 11111l 1I111iII iI 1111I11I 1 1i l 1 II 1111II I 11I|I1 V.8 1557 aatgacaaccacccagtctttaaggagacagagattgaagtcagtataccagaaaatgct 1616 V.1 1632 cctgtaggcacttcagtgacacagctccatgccacagatgctgacataggtgaaaatgcc 1691 V.8 1617 cctgtaggcacttcagtgacacagctccatgccacagatgctgacataggtgaaaatgcc 1676 V.1 1692 aagatccacttctctttcagcaatctagtctccaacattgccaggagattatttcacctc 1751 |||I 11 I1111 11 1 l 11 li ii|||| 1 11I llII III 1|I I1 I II II1 I I 1 V.8 1677 aagatccacttctctttcagcaatctagtctccaacattgccaggagattatttcacctc 1736 V.1 1752 aatgccaccactggacttatcacaatcaaagaaccactggatagggaagaaacaccaaac 1811 I l I l lI Iili i Ill III 11111 lil il 11I 1 lI II 1 l I1 lI II1 I 1 |11I111 I1 V.8 1737 aatgccaccactggacttatcacaatcaaagaaccactggatagggaagaaacaccaaac 1796 V.1 1812 cacaagttactggttttggcaagtgatggtggattgatgccagcaagagcaatggtgctg 1871 |1 l1 iiI II11I l I| l l 1llil I1 |1I I II1I111|II1 I 11 l11I11I l1 t1i I| V.8 :1797 cacaagttactggttttggcaagtgatggtggattgatgccagcaagagcaatggtgctg 1856 V.1 1872 gtaaatgttacagatgtcaatgataatgtcccatccattgacataagatacatcgtcaat 1931 V.8 1857 gtaaatgttacagatgtcaatgataatgtcccatccattgacataagatacatcgtcaat 1916 V.1 1932 cctgtcaatgacacagttgttctttcagaaaatattccactcaacaccaaaattgctctc 1991 WO 2004/098515 PCT/US2004/013568 292 1111111I l|1 I I 11111111l I| Il I I 1111 |1 | 11 I III l11 I I |11 11I1 I 1i I1 V.8 1917 cctgtcaatgacacagttgttctttcagaaaatattccactcaacaccaaaattgctctc 1976 V.1 1992 ataactgtgacggataaggatgcggaccataatggcagggtgacatgcttcacagatcat 2051 lI 1111l 1111 I l I lI i 1 I |I I 1 l 1 1 I i i i l i i| i| 1 I II II I| V.8 1977 ataactgtgacggataaggatgcggaccataatggcagggtgacatgcttcacagatcat 2036 V.1 2052 gaaatccctttcagattaaggccagtattcagtaatcagttcctcctggagactgcagca 2111 Hll 11111111111111111111111111111111111111111111 I 1111111 V.8 2037 gaaattcctttcagattaaggccagtattcagtaatcagttcctcctggagaatgcagca 2096 V.1 2112 tatcttgactatgagtccacaaaagaatatgccattaaattactggctgcagatgctggc 2171 V.8 2097 tatcttgactatgagtccacaaaagaatatgccattaaattactggctgcagatgctggc 2156 V.1 2172 aaacctcctttgaatcagtcagcaatgctcttcatcaaagtgaaagatgaaaatgacaat 2231 1 1 1 1 1 1 1 I l l l l l l l I l l i l l l l l l l l l l l l l l l l lI1l1i I l l l V.8 2157 aaacctcctttgaatcagtcagcaatgctcttcatcaaagtgaaagatgaaaatgacaat 2216 V.1 2232 gctccagttttcacccagtctttcgtaactgtttctattcctgagaataactctcctggC 2291 11 || ] 1 1 1 1 1 1 1 111 l I l I l l i ll l l l l l l l l l l [ I l l l l l I |11 11 I llII V.8 2217 gctccagttttcacccagtctttcgtaactgtttctattcctgagaataactctcctggc 2276 V.1 2292 atccagttgacgaaagtaagtgcaatggatgcagacagtgggcctaatgctaagatcaat 2351 lI1111111 11111111111111 1111111111111111111111111 11111111 V.8 2277 atccagttgatgaaagtaagtgcaacggatgcagacagtgggcctaatgctgagatcaat 2336 V.1 2352 tacctgctaggccctgatgctccacctgaattcagcctggattgtcgtacaggcatgctg 2411 V.8 2337 tacctgctaggccctgatgctccacctgaattcagcctggatcgtcgtacaggcatgctg 2396 V.1 2412 actgtagtgaagaaactagatagagaaaaagaggataaatatttattcacaattctggca 2471 l l illll i11 LI 11111 1 111|Il Ill illlll'lllllllll il ill1Ill1 ill V.8 2397 actgtagtgaagaaactagatagagaaaaagaggataaatatttattcacaattctggca 2456 V.1 2472 aaagataacggggtaccacccttaaccagcaatgtcacagtctttgtaagcattattgat 2531 V.8 2457 aaagataatggggtaccacccttaaccagcaatgtcacagtctttgtaagcattattgat 2516 V.1 2532 cagaatgacaatagcccagttttcactcacaatgaatacaacttctatgtcccagaaaac 2591 V.8 2517 cagaatgacaatagcccagttttcactcacaatgaatacaaattctatgtcccagaaaac 2576 V.1 2592 cttccaaggcatggtacagtaggactaatcactgtaactgatcctgattatggagacaat 2651 V.8 2577 cttccaaggcatggtacagtaggactaatcactgtaactgatcctgattatggagacaat 2636 V.1 2652 tctgcagttacgctctccattttagatgagaatgatgacttcaccattgattcacaaact 2711 111111111111111|111111||il|Illlllllllll I1llllllll l illllllll1 V.8 2637 tctgcagttacgctctccattttagatgagaatgatgacttcaccattgattcacaaact 2696 V.1 2712 ggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatcttacactttctat 2771 IV I2lll illlllllll 111111 11111111 Il Ill 11111 111111 Illll l2il5l 6 V.8 :2697 ggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatcttacactttctat 2756 WO 2004/098515 PCT/US2004/013568 293 V.1 2772 gtaaaggctgaggatggtggtagagtatcacgttcttcaagtgccaaagtaaccataaat 2831 i li l i l ll11111illiill lilli 1i I 1l1lll 11I1l 11I 111l 11Ili II1 l iII i l 111 I V.8 2757 gtaaaggctgaggatggtggtagagtatcacgttcttcaagtgccaaagtaaccataaat 2816 V.1 2832 gtggttgatgtcaatgacaacaaaccagttttcattgtccctccttccaactgttcttat 2891 lil1 ii I ilil I ll 1 I 111 111ll111 I i l iH 11 l l 1111111 V.8 2817 gtggttgatgtcaatgacaacaaaccagttttcattgtccctccttacaactattcttat 2876 V.1 2892 gaattggttctaccgtccactaatccaggcacagtggtctttcaggtaattgctgttgac 2951 1 Ili |1 11 li l i ll1 1 i lIIl lIIIIll 11 11 1|11 1 lilil V.8 2877 gaattggttctaccgtccactaatccaggcacagtggtctttcaggtaattgctgttgac 2936 V.1 2952 aatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaaacacaagagat 3011 l111 1il l 1 1 1 1 I I 1ill l111I lI l 1 Il i I I I 11l1i il I lI lI1 I I I1 l I1 I V.8 2937 aatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaaacacaagagat 2996 V.1 3012 ctgtttgcaatcgaccaagaaacaggcaacataacattgatggagaaatgtgatgttaca 3071 V.8 2997 ctgtttgcaatcgaccaagaaacaggcaacataacattgatggagaaatgtgatgttaca 3056 V.1 3072 gaccttggtttacacagagtgttggtcaaagctaatgacttaggacagcctgattctctc 3131 IilI l il l |I 1 1 1 1 I lllll11 I 1ll ll 11I 11i I I I I I I li1I|1l1l II V.B 3057 gaccttggtttacacagagtgttggtcaaagCtaatgacttaggacagcctgattctctc 3116 V.1 3132 ttcagtgttgtaattgtcaatctgttcgtgaatgagtcggtgaccaatgctacactgatt 3191 IIl ii l I lI l i Il l l l | 1111 11|11 11 11 1111111111 |II I l I I|1 V.8 3117 ttcagtgttgtaattgtcaatctgttcgtgaatgagtcagtgaccaatgctacactgatt 3176 V.1 3192 aatgaactggtgcgcaaaagcactgaagcaccagtgaccccaaatactgagatagctgat 3251 I l Iil II I lil1II 11 l I I|11I I I I11 l1111111111il111I 11I I 1I 1 I 1II| ||1l V.8 3177 aatgaactggtgcgcaaaagcattgaagcaccagtgaccccaaatactgagatagctgat 3236 V.1 3252 gtatcctcaccaactagtgactatgtcaagatcctggttgcagctgttgctggcaccata 3311 11iil111I11111il1lill 11I1| Iliil I11 l11|1l 11 l11Il 11111 l1111 V.8 3237 gtatcctcaccaactagtgactatgtcaagatcctggttgcagctgttgctggcaccata 3296 V.1 3312 actgtcgttgtagttattttcatcactgctgtagtaagatgtcgccaggcaccacacctt 3371 1 I l lii Ii i 11111 Il l l|| 1 l li il 111 |I | 1 I I l II l I II l I I Il V.8 3297 actgtcgttgtagttattttcatcactgctgtagtaagatgtcgccaggcaccacacctt 3356 V.1 3372 aaggctgctcagaaaaacaagcagaattctgaatgggctaccccaaacccagaaaacagg 3431 V.8 3357 aaggctgctcagaaaaacatgcagaattctgaatgggctaccccaaacccagaaaacagg 3416 V.1 3432 cagatgataatgatgaagaaaaagaaaaagaagaagaagcattcccctaagaacttgctg 3491 I l l I l l I l I I l l~ ~ill llI | I l I l I | Il I I I l I I I l I I I I I l Iii I 1I 1 V.8 3417 cagatgataatgatgaagaaaaagaaaaagaagaagaagcattcccctaagaacctgctg 3476 V.1 3492 cttaattttgtcactattgaagaaactaaggcagatgatgttgacagtgatggaaacaga 3551 Ii I i I IlllI l li lil11 11 11 1 I I 1 Ii 11 iI 11 I l I 11 II i I l V.8 3477 cttaatgttgtcactattgaagaaactaaggcagatgatgttgacagtgatggaaacaga 3536 V.1 3552 gtcacactagaccttcctattgatctagaagagcaaacaatgggaaagtacaattgggta 3611 lVl I.8I I i I l I I I 3 5l l l l l i l I l i l I | I | | I l | I I | l i l l i l l l I 3511 1 | I | V.8 :3537 gtcacactagaccttcctattgatctagaagagcaaacaatgggaaagtacaattgggta 3596 WO 2004/098515 PCT/US2004/013568 294 V.1 3612 actacacctactactttcaagcccgacagccctgatttggcccgacactacaaatctgcc 3671 Ill i I 11llll 11|||| 111 I 111ll lll I ll l ll l I lllll1 Ill il V.8 3597 actacacctactactttcaagcctgacagccctgatttggcccgacactacaaatctgcc 3656 V.1 3672 tctccacagcctgccttccaaattcagcctgaaactcccctgaattcgaagcaccacatc 3731 lI il 1|1111111111 II111111l 11lll 1l1ill 11111111 111111111 Ilil V.8 3657 tctccacagcctgccttccaaattcagcctgaaactcccctgaatttgaagcaccacatc 3716 V.1 3732 atccaagaactgcctctcgataacacctttgtggcctgtgactctatctccaagtgttcc 3791 ll I l i IIl 111111111 11111111111 111l lll II I l l i III V.8 3717 atccaagaactgcctctcgataacacctttgtggcctgtgactctatctccaattgttcc 3776 V.1 3792 tcaagcagttcagatccctacagcgtttctgactgtggctatccagtgacgaccttcgag 3851 l1 1 l 11l1lllll ll ll ll llil ll l1 il1 1 1 ||11 111111111 111111 I1 111111 V.8 3777 tcaagcagttcagatccctacagcgtttctgactgtggctatccagtgacaaccttcgag 3836 V.1 3852 gtacctgtgtccgtacacaccagaccg 3878 II111111111 Il l lEE 1 i i 11i I I i V.8 3837 gtacctgtgtccgtacacaccagaccg 3863 Score 1567 bits (815), Expect = 0.0Identities = 829/836 (99%) Strand = Plus / Plus V.1 3 ggtggtccagtacctccaaagatatggaatacactcctgaaatatcctgaaaactttttt 62 i i |IIiIi [11111 l I I1|1 I I 1 1 I II I 1 I I IIi 11 I I I 1111111 II V.8 1 ggtggtccagtacctccaaagatatggaatacactcctgaaatatcctgaaacctttttt 60 V.1 63 ttttcagaatcctttaataagcagttatgtcaatctgaaagttgcttacttgtactttat 122 1 | 11111 |li illllll ll lI ll ill Il 1111111111 l1 i l ill lllll V.8 61 ttttcagaatcctttaataagcagttatgtcaatctgaaagttgcttacttgtactttat 120 V.1 123 attaatagctattcttgtttttcttatccaaagaaaaatcctctaatccccttttcacat 182 V.8 :121 attaatagctattcttgtttttcttatccaaagaaaaatcctctaatccccttttcacat 180 V.1 183 gatagttgttaccatgtttaggcattagtcacatcaacccctctcctctcccaaacttct 242 Il lIElElEl1 11 1 1 I lllllll E l IEE l l il i I Il1( Il l 11111 1111 V.8 181 gatagttgttaccatgtttaggcgttagtcacatcaacccctctcctctcccaaacttct 240 V.1 243 cttcttcaaatcaaactttattagtccctcctttataatgattccttgcctcgttttatc 302 V.8 241 cttcttcaaatcaaactttattagtccctcctttataatgattccttgcctccttttatc 300 V.1 303 cagatcaattttttttcactttgatgcccagagctgaagaaatggactactgtataaatt 362 11E ||||EE 1|1El Ili l I E Il EElIElll IE l IEE El 1 1 I IIE I lI llE IElll I V.8 301 cagatcaattttttttcactttgatgcccagagctgaagaaatggactattgtataaatt 360 V.1 363 attcattgccaagagaataattgcattttaaacccatattataacaaagaataatgatta 422 11111 ||lllIEEE I llIIII lli111 llllilI l illlll1111I EE11 1lillll V.8 361 attcattgccaagagaataattgcattttaaacccatgttataacaaagaataatgatta 420 V.1 423 tattttgtgatttgtaacaaataccctttattttcccttaactattgaattaaatatttt 482 Ill I EE ill Ill|| il1111111 1EEE 1I lll E l E ] llE I llllll El l illill ill ill 8 V.8 :421 tattttgtgatttgtaacaaataccctttattttcccttaactattgaattaaatatttt 480 WO 2004/098515 PCT/US2004/013568 295 V.1 483 aattatttgtattctctttaactatcttggtatattaaagtattatcttttatatattta 542 I11 11 I lil11 l lll liII I l l 1 11 1 lll II 11 1 1 l Iiil V.8 481 aattatttgtattctctttaactatcttggtatattaaagtattatcttttatatattta 540 V.1 543 tcaatggtggacacttttataggtactctgtgtcatttttgatactgtaggtatcttatt 602 11 111 111 11 l il l l l l l l l l l l l l l l l l ll l ll l l l l l l 1 l i l l l l l V.8 541 tcaatggtggacacttttataggtactctgtgtcatttttgatactgtaggtatcttatt 600 v.1 603 tcatttatctttattcttaatgtacgaattcataatatttgattcagaacaaatttatca 662 11111111111111||11 iii 111111111111illlllil1lllli Illll V.8 601 tcatttatctttattcttaatgtacgaattcataatatttgattcagaacagatttatca 660 V.1 663 ctaattaacagagtgtcaattatgctaacatctcatttactgattttaatttaaaacagt 722 V.8 661 ctaattaacagagtgtcaattatgctaacatctcatttactgattttaatttaaaacagt 720 V.1 723 ttttgttaacatgcatgtttagggttggcttcttaataatttcttcttcctcttctctct 782 l ill1 ill il illl1lll1lllllllllllllllll1i|1111111 11Illlllllll V.8 721 ttttgttaacatgcatgtttagggttggcttcttaataatttcttcttcctcttctctct 780 V.1 783 ctcctcttcttttggtcagtgttgtgcgggttaatacaacaaactgtaacaagtgt 838 lilll11lll11111111l1 ii 1lll1llilllllllllllliii 11lill1| V.8 781 ctcctcttcttttggtcagtgttgtgcgggttaatacaacaaactgtcacaagtgt 836 Table LIV(g). Peptide sequences of protein coded by 109P1D4 v.8 (SEQ ID NO: 276) MFRVGFLIIS SSSSLSPLLL VSVVRVNTTN CHKCLLSGTY IFAVLLVCVV FHSGAQEKNY 60 TIREEIPENV LIGNLLKDLN LSLIPNKSLT TTMQFKLVYK TGDVPLIRTE EDTGETFTTG 120 ARIDREKLCA GTPRDEHCFY EVEVAILPDE IFRLVKIREL IEDTNDNAI FPATVINIST 180 PENSAINSKY TLPAAVDPDV GINGVQNYEL IKSQNIEGLD VIETPEGDKM PQLIVQKELD 240 REEKDTYVMK VKVEDGGFPQ RSSTAILQVS VTDTNDNHPV FKETEIEVSI PENAPVGTSV 300 TQLHATDADI GENAKIHFSF SNLVSNTARR LFHLNATTGL ITIKEPLDRE ETPNHKLLVL 360 ASDGGLMPAR AMVLVNVTDV NDNVPSIDIR YIVNPVNDTV VLSENIPLNT KIALTTVTDK 420 DADHNGRVTC FTDHEIPFRL RPVFSNQFLL ENAAYLDYES TKEYAIKLLA ADAGKPPLNQ 480 SAMLFIKVKD ENDNAPVFTQ SFVTVSTPEN NSPGIQL4KV SATDADSGPN AEINYLLGPD 540 APPEFSLDRR TGMLTVVKKL DREKEDKYLF TILAKDNGVP PLTSNVTVFV SIIDQNDNSP 600 VFTHNEYKFY VPENLPRHGT VGLITVTDPD YGDNSAVTLS ILDENDDFTI DSQTGVIRPN 660 ISFDREKQES YTFYVKAEDG GRVSRSSSAK VTINVVDVND NKPVFTVPPY NYSYELVLPS 720 TNPGTVVFQV IAVDNDTGMN AEVRYSIVGG NTRDLFAIDQ ETGNITLMEK CDVTDLCLHR 780 VLVKANDLGQ PDSLFSVVIV NLFVNESVTN ATLINELVRK SIEAPVTPNT EIADVSSPTS 840 DYVKILVAAV AGTITVVVVI FITAVVRCRQ APHLKAAQKN MQNSEWATPN PENRQMIMMK 900 KKKKKKKHSP KNLLLNVVTI EETKADDVDS DGNRVTLDLP IDLEEQTMGK YNWVTTPTTF 960 KPDSPDLARH YKSASPQPAF QIQPETFLNL KIHIIQELPL DNTFVACDSI SNCSSSSSDP 1020 YSVSDCGYPV TTFEVPVSVH TRPSQRRVTF HLPEGSQESS SDGGLGDHDA GSLTSTSHGL 1080 PLGYPQEEYF DRATPSNRTE GDGNSDPEST FIPGLKKEIT VQPTVEEASD NCTQECLIYG 1140 HSDACWMPAS LDHSSSSQAQ ASALCHSPPL SQASTQHHSP PVTQTIVLCH SPPVTQTIAL 1200 CHSPPPIQVS ALHHSPPLVQ GTALHHSPPS AQASALCYSP PLAQAAAISH SSSLPQVIAL 1260 HRSQAQSSVS LQQGWVQGAN GLCSVDQGVQ GSATSQFYTM SERLHPSDDS IKVIPLTTEA 1320 PRQQARPSRG DSPIMETHPL 1340 Table LV(g). Amino acid sequence alignment of IO9PID4v.1 (SEQ ID NO: 277) and 109P1D4 v.8 (SEQ ID NO: 278) Score 1961 bits (5081), Expect =O0.identities = 99211009 (98%), Positives =995/1009 (98%) V.1 3 LLSGTYTFAVLLACVVFHSGAQEKNYTIREEMPENVLIGDLLKDLNLSLIPNKSLTTI4Q 62 LLSGTYIFAVLL CVVFHSGAQEKNYTIREE PENVLIG+LLKDLNLSLIPNKSLTT MQ V.8 35 LLSGTYIFAVLLVCVVFHSGAQEKNYTIREEIPENVLIGNLLKDLNLSLIPNKSLTTTMQ 94 V.1 63 FKLVYKTGDVPLIRIEEDTGEIFTTG.RIDREI LCAGIPRDEHCFYEVEVAILPDEIFRL 122 FKLVYKTGDVPLIRIEEDTGEI FTTGARIDREKLCAG IPRDEHCFYEVEVAILPDEIFRL V.8 95 FKLVYKTGDVPLIRIEEDTGEIFTTGRIDRELCAGIPRDEHCFYEVEVAILPDEIFRL 154 WO 2004/098515 PCT/US2004/013568 296 V.1 123 VKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIKSQ 182 VKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIKSQ V.8 155 VKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIKSQ 214 V.1 183 NIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVTDT 242 NIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVTDT V.8 215 NIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVTDT 274 V.1 243 NDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLFHL 302 NDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIEHFSFSNLVSNIARRLFHL V.8 275 NDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLFHL 334 V.1 303 NATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYIVN 362 NATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYIVN V.8 335 NATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYIVN 394 V.1 363 PVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLETAA 422 PVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLE AA V.8 395 PVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLENAA 454 V.1 423 YLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNSPG 482 YLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNSPG V.8 455 YLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNSPG 514 V.1 483 IQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTVVKKLDREKEDKYLFTILA 542 IQL KVSA DADSGPNA+INYLLGPDAPPEFSLD RTGMLTVVKKLDREKEDKYLFTILA V.8 515 IQLMKVSATDADSGPNAEINYLLGPDAPPEFSLDRRTGMLTVVKKLDREKEDKYLFTILA 574 V.1 543 KDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYGDN 602 KDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEY FYVPENLPRHGTVGLITVTDPDYGDN V.8 575 KDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYKFYVPENLPRHGTVGLITVTDPDYGDN 634 V.1 603 SAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVTIN 662 SAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVTIN V.8 635 SAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVTIN 694 V.1 663 VVDVNDNKPVFIVPPSNCSYELVLPSTNPGTVVFQVIAVDNDTGMNAEVRYSIVGGNTRD 722 VVDVNDNKPVFIVPP N SELVLPSTNPGTVVFQVIAVDNDTGMNAEVRYSIVGGNTRD V.8 695 VVDVNDNKPVFIVPPYNYSYELVLPSTNPGTVVFQVIAVDNDTGMNAEVRYSIVGGNTRD 754 V.1 723 LFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSVVIVNLFVNESVTNATLI 782 LFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSVVIVNLFVNESVTNATLI V.8 755 LFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSVVIVNLFVNESVTNATLI 814 V.1 783 NELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVVVVIFITAVVRCRQAPHL 842 NELVRKS EAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVVVVIFITAVVRCRQAPHL V.8 815 NELVRKSIEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVVVVIFITAVVRCRQAPHL 874 V.1 843 KAAQKNKQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDGNR 902 KAAQKN QNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLN VTIEETKADDVDSDGNR V.8 875 KAAQKNMQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNVVTIEETKADDVDSDGNR 934 V.1 903 VTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNSKHHI 962 VTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLN KHHI V.8 935 VTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNLKHHI 994 V.1 963 IQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP 1011 IQELPLDNTFVACDSIS CSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP V.8 995 IQELPLDNTFVACDSISNCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP 1043 Table 111(h). Nucleotide sequence of transcript variant 109P1D4 v.9 (SEQ ID NO: 279) cccatttctc cccctctgtt aagtccctcc ccctcgccat tcaaaagggc tggctcggca 60 ctggctcctt gcagtcggcg aactgtctgg gcgggaggag ccgtgagcag tagctgcact 120 cagctgcccg cgcggcaaag aggaaggcaa gccaaacaga gtgcgcagag tggcagtgcc 180 agcggcgaca caggcagcac aggcagcccg ggctgcctga atagcctcag aaacaacctc 240 agcgactccg gctgctctgc ggactgcgag ctgtggcggt agagcccgct acagcagtcg 300 cagtctccgt ggagcgggcg gaagcctttt ttctcccttt cgtttacctc ttcattctac 360 WO 2004/098515 PCT/US2004/013568 297 tctaaaggca tcgttattag gaaaatcctg ttgtgaataa gaaggattcc acagatcaca 420 taccagagcg gttttgcctc agctgctctc aactttgtaa tcttgtgaag aagctgacaa 480 gcttggctga ttgcagtgca ctatgaggac tgaatgacag tgggttttaa ttcagatatt 540 tcaagtgttg tgcgggttaa tacaacaaac tgtcacaagt gtttgttgtc cgggacgtac 600 attttcgcgg tcctgctagt atgcgtggtg ttccactctg gcgcccagga gaaaaactac 660 accatccgag aagaaattcc agaaaacgtc ctgataggca acttgttgaa agaccttaac 720 ttgtcgctga ttccaaacaa gtccttgaca actactatgc agttcaagct agtgtacaag 780 accggagatg tgccactgat tcgaattgaa gaggatactg gtgagatctt cactaccggc 840 gctcgcattg atcgtgagaa attatgtgct ggtatcccaa gggatgagca ttgcttttat 900 gaagtggagg ttgccatttt gccggatgaa atatttagac tggttaagat acgttttctg 960 atagaagata taaatgataa tgcaccattg ttcccagcaa cagttatcaa catatcaatt 1020 ccagagaact cggctataaa ctctaaatat actctcccag cggctgttga tcctgacgta 1080 ggcataaacg gagttcaaaa ctacgaacta attaagagtc aaaacatttt tggcctcgat 1140 gtcattgaaa caccagaagg agacaagatg ccacaactga ttgttcaaaa ggagttagat 1200 agggaagaga aggataccta tgtgatgaaa gtaaaggttg aagatggtgg ctttcctcaa 1260 agatacagta ctgctatttt gcaagtaagt gttactgata caaatgacaa ccacccagtc 1320 tttaaggaga cagagattga agtcagtata ccagaaaatg ctcctgtagg cacttcagtg 1380 acacagctcc atgccacaga tgctgacata ggtgaaaatg ccaagatcca cttctctttc 1440 agcaatctag tctecaacat tgccaggaga ttatttcacc tcaatgccac cactggactt 1500 atcacaatca aagaaccact ggatagggaa gaaacaccaa accacaagtt actggttttg 1560 gcaagtgatg gtggattgat gccagcaaga gcaatggtgc tggtaaatgt tacagatgtc 1620 aatgataatg tcccatccat tgacataaga tacatcgtca atcctgtcaa tgacacagtt 1680 gttctttcag aaaatattcc actcaacacc aaaattgctc tcataactgt gacggataag 1740 gatgcggacc ataatggcag ggtgacatgc ttcacagatc atgaaattcc tttcagatta 1800 aggccagtat tcagtaatca gttcctcctg gagaatgcag catatcttga ctatgagtcc 1860 acaaaagaat atgccattaa attactggct gcagatgctg gcaaacctcc tttgaatcag 1920 tcagcaatgc tcttcatcaa agtgaaagat gaaaatgaca atgctccagt tttcacccag 1980 tctttcgtaa ctgtttctat tcctgagaat aactctcctg gcatccagtt gatgaaagta 2040 agtgcaacgg atgcagacag tgggcctaat gctgagatca attacctgct aggccctgat 2100 gctccacctg aattcagcct ggatcgtcgt acaggcatgc tgactgtagt gaagaaacta 2160 gatagagaaa aagaggataa atatttattc acaattctgg caaaagataa tggggtacca 2220 cccttaacca gcaatgtcac agtctttgta agcattattg atcagaatga caatagccca 2280 gttttcactc acaatgaata caaattctat gtcccagaaa accttccaag gcatggtaca 2340 gtaggactaa tcactgtaac tgatcctgat tatggagaca attctgcagt tacgctctcc 2400 attttagatg agaatgatga cttcaccatt gattcacaaa ctggtgtcat ccgaccaaat 2460 atttcatttg atagagaaaa acaagaatct tacactttct atgtaaaggc tgaggatggt 2520 ggtagagtat cacgttcttc aagtgccaaa gtaaccataa atgtggttga tgtcaatgac 2580 aacaaaccag ttttcattgt ccctccttac aactattctt atgaattggt tctaccgtcc 2640 actaatccag gcacagtggt ctttcaggta attgctgttg acaatgacac tggcatgaat 2700 gcagaggttc gttacagcat tgtaggagga aacacaagag atctgtttgc aatcgaccaa 2760 gaaacaggca acataacatt gatggagaaa tgtgatgtta cagaccttgg tttacacaga 2820 gtgttggtca aagctaatga cttaggacag cctgattctc tcttcagtgt tgtaattgtc 2880 aatctgttcg tgaatgagtc agtgaccaat gctacactga ttaatgaact ggtgcgcaaa 2940 agcattgaag caccagtgac cccaaatact gagatagctg atgtatcctc accaactagt 3000 gactatgtca agatcctggt tgcagctgtt gctggcacca taactgtcgt tgtagttatt 3060 ttcatcactg ctgtagtaag atgtcgccag gcaccacacc ttaaggctgc tcagaaaaac 3120 atgcagaatt ctgaatgggc taccccaaac ccagaaaaca ggcagatgat aatgatgaag 3180 aaaaagaaaa agaagaagaa gcattcccct aagaacctgc tgcttaatgt tgtcactatt 3240 gaagaaacta aggcagatga tgttgacagt gatggaaaca gagtcacact agaccttcct 3300 attgatctag aagagcaaac aatgggaaag tacaattggg taactacacc tactactttc 3360 aagcctgaca gccctgattt ggcccgacac tacaaatctg cctctccaca gcctgccttc 3420 caaattcagc ctgaaactcc cctgaatttg aagcaccaca tcatccaaga actgcctctc 3480 gataacacct ttgtggcctg tgactctatc tccaattgtt cctcaagcag ttcagatccc 3540 tacagcgttt ctgactgtgg ctatccagtg acaaccttcg aggtacctgt gtccgtacac 3600 accagaccga ctgattccag gacatgaact attgaaatct gcagtgagat gtaactttct 3660 aggaacaaca aaattccatt ccccttccaa aaaatttcaa tgattgtgat ttcaaaatta 3720 ggctaagatc attaattttg taatctagat ttcccattat aaaagcaagc aaaaatcatc 3780 ttaaaaatga tgtcctagtg aaccttgtgc tttctttagc tgtaatctgg caatggaaat 3840 ttaaaattta tggaagagac agtgcagcgc aataacagag tactctcatg ctgtttctct 3900 gtttgctctg aatcaacagc catgatgtaa tataaggctg tcttggtgta tacacttatg 3960 gttaatatat cagtcatgaa acatgcaatt acttgccctg tctgattgtt gaataattaa 4020 aacattatct ccaggagttt ggaagtgagc tgaactagcc aaactactct ctgaaaggta 4080 WO 2004/098515 PCT/US2004/013568 298 tccagggcaa gagacatttt taagacccca aacaaacaaa aaacaaaacc aaaacactct 4140 ggttcagtgt tttgaaaata ttgactaaca taatattgct gagaaaatca tttttattac 4200 ccaccactct gcttaaaagt tgagtgggcc gggcgcggtg gctcacgcct gtaattccag 4260 cactttggga ggccgaggcg ggtggatcac gaggtcagqa tattgagacc atcctggcta 4320 acatggtgaa accccatctc cactaaaaat acaaaaaatt agctgggcgt ggtggcgggc 4380 gcctgtagtc ccagctactc gggaggctga ggoaggagaa tggcgtgaac ccgggaggcg 4440 gagcttgcag tgagccgaga tgqcgccact gcactccagc ctgqgtgaca gagcaagact 4500 ctgtctcaaa aagaaaaaaa tgttcagtga tagaaaataa ttttactagg tttttatgtt 4560 gattgtactc atgctgttcc actcctttta attattaaaa agttattttt ggctcggtgt 4620 ggtggctcat acctgtaatc ccagcacttt gggaggccga ggcgggtgga tcacctgagg 4680 tcaggagttc aagaccagtc tggccaacat 4710 Table 1-I11(h). Nucleotide sequence alignment of 1 09P1 D4 M. (SEQ ID NO: 280) and 1 09P1 D4 v.9 (SEQ ID NO: 281) Score 5664 bits (2946), Expect = 0.Oldentities = 3000/3027 (99%) Strand =Plus / Plus V.1 852 ttgttgtccgggacgtacattttcgcggtcctgctagcatgcgtggtgttccactctgc 911 V.9 583 ttgttgtccgggacgtacattttcgcggtcctgctagtatgcgtggtgttccactctggc 642 V.1 912 gcccaggagaaaaactacaccatccgagaagaaatgccagaaaacgtcctgataggcgac 971 V.9 643 gcgcaggagaaaaactacaccatccgagaagaaattccagaaaacgtcctgataggcaac 702 V.1 972 t ttgtg 1031 V.9 703 ttgttgaaagaccttaacttgtcgctgattccaaacaagtccttgacaactactatgca 762 V.1 1032 cagac t 1091 V.9 763 ttcaagctagtgtacaagaccggagatgtgccactgattcgaattgaagaggatactggt 822 V.1 1092 gaactatcgcccctgtctaaatttcgttcag 1151 V. 9 823 gaactatcgcccctgtctaaatttcgttcag 882 V.1 1152 gatgagcattgcttttatgaagtggaggttgccattttgccggatgaaatatttagactg 1211 V.9 883 gafigagcattgcttttatgaagtggaggttgccattttgccggatgaaatatttagactg 942 V.1 1212 gagta ga V. 9 943 gttaagatacgttttctgatagaagatataaatgataatgcaccattgttcccagcaaca 1002 V.1 1272 4 1331 V.9 1003 4 1062 V.1 1332 gctgttgatcctgacgtaggaataaacggagttcaaactacgaactaattaagatcaa 1391 V.9 1063 gctgttgatcctgacgtaggcataaaCggagttcaaaactacgaactaattaagagcaa 1122 V.1 1392 a 1451 V.9 1123 ~aaatttttggcctcgatgtcattgaaCacccagaaggagacaagatgccacaactgatt 1182 V.1 1452 gttcaaaaggagttagatagggaagagaaggatacctacgtatgaaagtaaagttgaa 1511 agttattttt ggctgggtgt 462 WO 2004/098515 PCT/US2004/013568 299 V.9 1183 gttcaaaaggagttagatagggaagagaaggatacctatgtgatgaaagtaaaggttgaa 1242 V.1 1512 gatggtggctttcctcaaagatccagtactgctattttgcaagtgagtgttactgataca 1571 111ll 1l 11l111|I 1I 1IIIl 1I||Ill 11ll 111 liii11 111I IIII | II l V.9 1243 gatggtggctttcctcaaagatccagtactgctattttgcaagtaagtgttactgataca 1302 V.1 1572 aatgacaaccacccagtctttaaggagacagagattgaagtcagtataccagaaaatgct 1631 Ili 111Il1l I i1 1 II 111 ill IlI ll lIII 1 l i 1 IIll111111111 V.9 1303 aatgacaaccacccagtctttaaggagacagagattgaagtcagtataccagaaaatgct 1362 V.1 1632 cctgtaggcacttcagtgacacagctccatgccacagatgctgacataggtgaaaatgcc 1691 V.9 1363 cctgtaggcacttcagtgacacagctccatgccacagatgctgacataggtgaaaatgcc 1422 V.1 1692 aagatccacttctctttcagcaatctagtctccaacattgccaggagattatttcacctc 1751 11I l Il1111ll 1l I l i i 1 1 1 11i I l lI lI I1 I II I II 11 i II I V.9 1423 aagatccacttctctttcagcaatctagtctccaacattgccaggagattatttcacctc 1482 V.1 1752 aatgccaccactggacttatcacaatcaaagaaccactggatagggaagaaacaccaaac 1811 V. 9 1483 aatgccaccactggacttatcacaatcaaagaaccactggatagggaagaaacaccaaac 1542 V.1 1812 cacaagttactggttttggcaagtgatggtggattgatgccagcaagagcaatggtgctg 1871 11 1111 11 I11l i 1II l I 11llll 11l1 Ill1ll111 Ill I V.9 1543 cacaagttactggttttggcaagtgatggtggattgatgccagcaagagcaatggtgctg 1602 V.1 1872 gtaaatgttacagatgtcaatgataatgtcccatccattgacataagatacategtcaat 1931 V.9 1603 gtaaatgttacagatgtcaatgataatgtcccatccattgacataagatacatcgtcaat 1662 V.1 1932 cctgtcaatgacacagttgttctttcagaaaatattccactcaacaccaaaattgctctc 1991 1 11111IIl 11 1 1 11ll11 1 1 11 1 1111111111II l l l ll l II l l1 I ll l l iii V.9 1663 cctgtcaatgacacagttgttctttcagaaaatattccactcaacaccaaaattgctctc 1722 V.1 1992 ataactgtgacggataaggatgcggaccataatggcagggtgacatgcttcacagatcat 2051 V.9 1723 ataactgtgacggataaggatgcggaccataatggcagggtgacatgcttcacagatcat 1782 V.1 2052 gaaatccctttcagattaaggccagtattcagtaatcagttcctcctggagactgcagca 2111 ill i lill1 llllI l1 llllll1 lllilll1 l1 lillli1 ll11 l1 ll1 I lli1 l11 V.9 1783 gaaattcctttcagattaaggccagtattcagtaatcagttcctcctggagaatgcagca 1842 V.1 2112 tatcttgactatgagtccacaaaagaatatgccattaaattactggctgcagatgctggc 2171 1|Ill111 Illll Il 111l 11I1lIlll I 1Ill 1 I 11l111l iI lI l lil l II I11 1 1 1 1 1 V.9 1843 tatcttgactatgagtccacaaaagaatatgccattaaattactggctgcagatgctggc 1902 V.1 2172 aaacctcctttgaatcagtcagcaatgctcttcatcaaagtgaaagatgaaaatgacaat 2231 V.9 1903 aaacctcctttgaatcagtcagcaatgctcttcatcaaagtgaaagatgaaaatgacaat 1962 V.1 2232 gctccagttttcacccagtctttcgtaactgtttctattcctgagaataactctcctggc 2291 ll1 i II il 1 1illl ll l I l IlI I II111 ll1 11 I11 II1111 il111l V.9 1963 getccagttttcacccagtctttcgtaactgtttctattcctgagaataactctcctggc 2022 V.1 2292 atccagttgacgaaagtaagtgcaatggatgcagacagtgggcctaatgctaagatcaat 2351 WO 2004/098515 PCT/US2004/013568 300 V.9 2023 atccagttgatgaaagtaagtgcaacggatgcagacagtgggcctaatgctgagatcaat 2082 V.1 2352 tacctgctaggccctgatgctccacctgaattcagcctggattgtcgtacaggcatgctg 2411 l lI Iliiil I i ll il11 11 il il I111ll 111I1Il l II V.9 2083 tacctgotaggccctgatgctccacctgaattcagcctggatcgtcgtacaggcatgetg 2142 V.1 2412 actgtagtgaagaaactagatagagaaaaagaggataaatatttattcacaattctggca 2471 lIl I IlIIIIIIIII 111 I11 I i 111I I 11I1I I I I 11111I11 IiI V.9 2143 actgtagtgaagaaactagatagagaaaaagaggataaatatttattcacaattctggca 2202 V.1 2472 aaagataacggggtaccaccettaaccagcaatgtcacagtctttgtaagcattattgat 2531 liiiiiI 11111111111111 IIII11ill111ll1l11l111llilII V.9 2203 aaagataatggggtaccaccettaaccagcaatgtcacagtctttgtaagcattattgat 2262 V.1 2532 cagaatgacaatagcccagttttcactcacaatgaatacaacttctatgtcccagaaaac 2591 11 1 1 1 1 l l IllllllllI 11lllll1 illl 1 1 11111 111111 111 V.9 2263 cagaatgacaatagcccagttttcactcacaatgaatacaaattctatgtcccagaaaac 2322 V.1 2592 cttccaaggcatggtacagtaggactaatcactgtaactgatcctgattatggagacaat 2651 lllll ill!Ill111111II1 ll 111l 11 11I IIlI 111l1 1 li V.9 2323 cttccaaggcatggtacagtaggactaatcactgtaactgatcctgattatggagacaat 2382 V.1 2652 tctgcagttacgctctccattttagatgagaatgatgacttcaccattgattcacaaact 2711 111111 II11 1 1 l1llll ll Illlllll Ill 1 111 ill1 i1II V.9 2383 tctgcagttacgctctccattttagatgagaatgatgacttcaccattgattcacaaact 2442 V.1 2712 ggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatcttacactttctat 2771 V.9 2443 ggtgtcatccgaccaaatatttcatttgatagagaaaaacaagaatcttacactttctat 2502 V.1 2772 gtaaaggctgaggatggtggtagagtatcacgttcttcaagtgccaaagtaaccataaat 2831 V.9 2503 gtaaaggetgaggatggtggtagagtatcacgttcttcaagtgccaaagtaaccataaat 2562 V.1 2832 gtggttgatgtcaatgacaacaaaccagttttcattgtccctccttccaactgttcttat 2891 Ill I Il1Ill 11ll 1Illll Il Ill Il III1 1 1 1 1 1 1 1 1 I II 111 V.9 2563 gtggttgatgtcaatgacaacaaaccagttttcattgtccctccttacaactattcttat 2622 V.1 2892 gaattggttctaccgtccactaatccaggcacagtggtctttcaggtaattgctgttgac 2951 V.9 2623 gaattggttctaccgtccactaatccaggcacagtggtctttcaggtaattgctgttgac 2682 V.1 2952 aatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaaacacaagagat 3011 V.9 2683 aatgacactggcatgaatgcagaggttcgttacagcattgtaggaggaaacacaagagat 2742 V.1 3012 ctgtttgcaatcgaccaagaaacaggcaacataacattgatggagaaatgtgatgttaca 3071 illlll Il111111111111 11|Ill III 1llll 1II IIIl 11II 1I 1IIIII1I1 V.9 2743 ctgtttgcaatcgaccaagaaacaggcaacataacattgatggagaaatgtgatgttaca 2802 V.1 3072 gaccttggtttacacagagtgttggtcaaagctaatgacttaggacagcctgattctctc 3131 V. i2l l l11i I ll 111111111111111III ll l iIIIII III IIIIt 2862 V.9 :2803 gactgtaaaattgtaagtagctgaactattt 2862 WO 2004/098515 PCT/US2004/013568 301 V.1 3132 ttcagtgttgtaattgtcaatctgttcgtgaatgagtcggtgaccaatgctacactgatt 3191 1111111 I 1lll ll lllli Ill1Ill1 lll1ll Ill 11 1 li i II I I V.9 2863 ttcagtgttgtaattgtcaatctgttcgtgaatgagtcagtgaccaatgctacactgatt 2922 V.1 3192 aatgaactggtgcgcaaaagcactgaagcaccagtgaccccaaatactgagatagctgat 3251 1 1 1 1 1 1 1 1 1 1l l l i l l 11 i l i l l l l l l l l l l I l l I I I I I I I I I I I I I I I I 1 V.9 2923 aatgaactggtgcgcaaaagcattgaagcaccagtgaccccaaatactgagatagctgat 2982 V.1 3252 gtatcctcaccaactagtgactatgtcaagatcetggttgcagctgttgetggcaccata 3311 Ill I Ill Ill111 11 1111llll1Ill 1||i1Il i II1II V.9 2983 gtatcctcaccaactagtgactatgtcaagatcctggttgcagctgttgetggcaccata 3042 V.1 3312 actgtcgttgtagttattttcatcactgctgtagtaagatgtcgccaggcaccacacctt 3371 1111111111|| 111111111Il1 lii 11111111111liill V.9 3043 actgtcgttgtagttattttcatcactgctgtagtaagatgtcgccaggcaccacacctt 3102 V.1 3372 aaggctgetcagaaaaacaagcagaattctgaatgggctaccccaaacccagaaaacagg 3431 1111111 l Il l111i 111i111111111111 I V.9 3103 aaggetgctcagaaaaacatgcagaattctgaatgggctaccccaaacccagaaaacagg 3162 V.1 3432 cagatgataatgatgaagaaaaagaaaaagaagaagaagcattcccctaagaacttgctg 3491 V.9 3163 cagatgataatgatgaagaaaaagaaaaagaagaagaagcattcccctaagaacctgctg 3222 V.1 3492 cttaattttgtcactattgaagaaactaaggcagatgatgttgacagtgatggaaacaga 3551 l 11I 1Ill 111l il lll lllli Illl i Illl 1 il I1 111 11 1 V.9 3223 cttaatgttgtcactattgaagaaactaaggcagatgatgttgacagtgatggaaacaga 3282 V.1 3552 gtcacactagaccttcctattgatctagaagagcaaacaatgggaaagtacaattgggta 3611 111111 111111111111 I 11 l l l lil l lill II ll l i i II1 ll111 I1 I V.9 3283 gtcacactagaccttcctattgatctagaagagcaaacaatgggaaagtacaattgggta 3342 V.1 3612 actacacctactactttcaagcccgacagccctgatttggcccgacactacaaatctgcc 3671 V.9 3343 actacacctactactttcaagcctgacagccctgatttggcccgacactacaaatctgcc 3402 V.1 3672 tctccacagcctgccttccaaattcagcctgaaactcccctgaattcgaagcaccacatc 3731 1I l i ll I Illll11 11 11lll1 111il1 illl1111IIIIII ii V.9 3403 tctccacagcctgccttccaaattcagcctgaaactcccctgaatttgaagcaccacatc 3462 V.1 3732 atccaagaactgcctctcgataacacctttgtggcctgtgactctatctccaagtgttcc 3791 111111III1I1lllll1 l III111111 111l1 I!1111ll111 V.9 3463 atccaagaactgcctctcgataacacctttgtggcctgtgactctatctccaattgttc 3522 V.1 3792 tcaagcagttcagatccctacagcgtttctgactgtggctatccagtgacgaccttcgag 3851 i Illl ill lilllll IIII ll l IIII11 ll1 IIII1 IIIIII1 II11 |II 111111 V.9 3523 tcaagcagttcagatccctacagcgtttctgactgtggetatccagtgacaaccttegag 3582 V.1 3852 gtacctgtgtccgtacacaccagaccg 3878 V.9 3583 gtacctgtgtccgtacacaccagaccg 3609 Table LIV(h). Peptide sequences of protein coded by 109PID4 v.9 (SEQ ID NO: 282) MTVGFNSDIS SVVRVNTTNC HKCLLSGTYI FAVLLVCVVF HSGAQEKNYT IREEIPENVL 60 IGNLLKDLNL SLIPNKSLTT TMQFKLVYKT GDVPLIRIEE DTGEIFTTGA RIDREKLCAG 120 IPRDEHCFYE VEVAILPDEI FRLVKIRFLI EDINDNAPLF PATVINISIP ENSAINSKYT 180 WO 2004/098515 PCT/US2004/013568 302 LPAAVDPDVG INGVQNYELI KSQNIFGLDV IETPEGDKMP QLIVQKELDR EEKDTYVMKV 240 KVEDGGFPQR SSTAILQVSV TDTNDNHPVF KETEIEVSIP ENAPVGTSVT QLHATDADIG 300 ENAKIHFSFS NLVSNIARRL FHLNATTGLI TIKEPLDREE TPNHKLLVLA SDGGLMPARA 360 MVLVNVTDVN DNVPSIDIRY IVNPVNDTVV LSENIPLNTK IALTTVTDKD ADHNGRVTCF 420 TDHEIPFRLR PVFSNQFLLE NAAYLDYEST KEYAIKLLAA DAGKPPLNQS AMLFIKVKDE 480 NDNAPVFTQS FVTVSIPENN SPGIQLMKVS ATDADSGPNA EINYLLGPDA PPEFSLDRRT 540 GMLTVVKKLD REKEDKYLFT ILAKDNGVPP LTSNVTVFVS IIDQNDNSPV FTHNEYKFYV 600 PENLPRHGTV GLITVTDPDY GDNSAVTLSI LDENDDFTID SQTGVIRPNI SFDREKQESY 660 TFYVKAEDGG RVSRSSSAKV TINVVDVNDN KPVFIVPPYN YSYELVLPST NPGTVVFQVI 720 AVDNDTGMNA EVRYSIVGGN TRDLFAIDQE TGNITLMEKC DVTDLGLHRV LVKANDLGQP 780 DSLFSVVIVN LFVNESVTNA TLINELVRKS IEAPVTPNTE IADVSSPTSD YVKILVAAVA 840 GTITVVVVIF ITAVVRCRQA PHLKAAQKNM QNSEWATPNP ENRQMIMMKK KKKKKKHSPK 900 NLLLNVVTIE ETKADDVDSD GNRVTLDLPI DLEEQTMGKY NWVTTPTTFK PDSPDLARHY 960 KSASPQPAFQ IQPETPLNLK HHIIQELPLD NTFVACDSIS NCSSSSSDPY SVSDCGYPVT 1020 TFEVPVSVHT RPTDSRT 1037 Table LV(h). Amino acid sequence alignment of 109P1D4 v. (SEQ ID NO: 283) and I09PID4 v.9 (SEQ ID NO: 284) Score 1961 bits (5081), Expect = 0.01dentities = 992/1009 (98%), Positives = 995/1009 (98%) V.1 3 LLSGTYIFAVLLACVVFHSGAQEKNYTIREEMPENVLTGDLLKDLNLSLIPNKSLTTAMQ 62 LLSGTYIFAVLL CVVFHSGAQEKNYTIREE+PENVLIG+LLKDLNLSLIPNKSLTT MQ V.9 24 LLSGTYIFAVLLVCVVFHSGAQEKNYTIREEIPENVLIGNLLKDLNLSLIPNKSLTTTMQ 83 V.1 63 FKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIFRL 122 FKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIFRL V.9 84 FKLVYKTGDVPLIRIEEDTGEIFTTGARIDREKLCAGIPRDEHCFYEVEVAILPDEIFRL 143 V.1 123 VKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIKSQ 182 VKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIKSQ V.9 144 VKIRFLIEDINDNAPLFPATVINISIPENSAINSKYTLPAAVDPDVGINGVQNYELIKSQ 203 V.1 183 NIFGLDVIETPEGDKMQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVTDT 242 NIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVTDT V.9 204 NIFGLDVIETPEGDKMPQLIVQKELDREEKDTYVMKVKVEDGGFPQRSSTAILQVSVTDT 263 V.1 243 NDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLFHL 302 NDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLFHL V.9 264 NDNHPVFKETEIEVSIPENAPVGTSVTQLHATDADIGENAKIHFSFSNLVSNIARRLFHL 323 V.1 303 NATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYIVN 362 NATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYIVN V.9 324 NATTGLITIKEPLDREETPNHKLLVLASDGGLMPARAMVLVNVTDVNDNVPSIDIRYIVN 383 V.1 363 PVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLETAA 422 PVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLE AA V.9 384 PVNDTVVLSENIPLNTKIALITVTDKDADHNGRVTCFTDHEIPFRLRPVFSNQFLLENAA 443 V.1 423 YLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNSPG 482 YLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNSPG V.9 444 YLDYESTKEYAIKLLAADAGKPPLNQSAMLFIKVKDENDNAPVFTQSFVTVSIPENNSPG 503 V.1 483 IQLTKVSAMDADSGPNAKINYLLGPDAPPEFSLDCRTGMLTVVKKLDREKEDKYLFTILA 542 IQL KVSA DADSGPNA+INYLLGPDAPPEFSLD RTGMLTVVKKLDREKEDKYLFTILA V.9 504 IQLMKVSATDADSGPNAEINYLLGPDAPPEFSLDRRTGMLTVVKKLDREKEDKYLFTILA 563 V.1 543 KDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYNFYVPENLPRHGTVGLITVTDPDYGDN 602 KDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEY FYVPENLPRHGTVGLITVTDPDYGDN V.9 564 KDNGVPPLTSNVTVFVSIIDQNDNSPVFTHNEYKFYVPENLPRHGTVGLITVTDPDYGDN 623 V.1 603 SAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVTIN 662 SAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVTIN V.9 624 SAVTLSILDENDDFTIDSQTGVIRPNISFDREKQESYTFYVKAEDGGRVSRSSSAKVTIN 683 V.1 663 VVDVNDNKPVFIVPPSNCSYELVLPSTNPGTVVFQVIAVDNDTGMNAEVRYSIVGGNTRD 722 VVDVNDNKPVFIVPP N SYELVLPSTNPGTVVFQVIAVDNDTGMNAEVRYSIVGGNTRD V.9 684 VVDVNDNKPVFIVPPYNYSYELVLPSTNPGTVVFQVIAVDNDTGMNAEVRYSIVGGNTRD 743 WO 2004/098515 PCT/US2004/013568 303 V.1 723 LFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSVVIVNLFVNESVTNATLI 782 LFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSVVIVNLFVNESVTNATLI V.9 744 LFAIDQETGNITLMEKCDVTDLGLHRVLVKANDLGQPDSLFSVVIVNLFVNESVTNATLI 803 V.1 783 NELVRKSTEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVVVVIFITAVVRCRQAPHL 842 NELVRKS EAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVVVVIFITAVVRCRQAPHL V.9 804 NELVRKSIEAPVTPNTEIADVSSPTSDYVKILVAAVAGTITVVVVIFITAVVRCRQAPHL 863 V.1 843 KAAQKNKQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNFVTIEETKADDVDSDGNR 902 KAAQKN QNSEWATPNPENRQMIMMKIKKKKKIKKHSPIN<LLLN VTIEETKADDVDSDGNR V.9 664 KAAQKNMQNSEWATPNPENRQMIMMKKKKKKKKHSPKNLLLNVVTIEETKADDVDSDGNR 923 V.1 903 VTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNSKHHI 962 VTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLN KHHI V.9 924 VTLDLPIDLEEQTMGKYNWVTTPTTFKPDSPDLARHYKSASPQPAFQIQPETPLNLKHHI 983 V.1 963 IQELPLDNTFVACDSISKCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP 1011 IQELPLDNTFVACDSIS CSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP V.9 984 IQELPLDNTFVACDSISNCSSSSSDPYSVSDCGYPVTTFEVPVSVHTRP 1032

Claims

1. A composition that comprises: a) a peptide of eight, nine, ten, or eleven contiguous amino acids of a protein of Figure 2; b) a peptide of Tables VIII-XXI; c) a peptide of Tables XXII to XLV; or, d) a peptide of Tables XLVI to XLIX.

2. A composition of claim 1, which elicits an immune response.

3. A protein of claim 2 that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% homologous or identical to an entire amino acid sequence shown in Figure 2.

4. A protein of claim 2, which is bound by an antibody that specifically binds to a protein of Figure 2.

5. A composition of claim 2 wherein the composition comprises a cytotoxic T cell (CTL) polypeptide epitope or an analog thereof, from the amino acid sequence of a protein of Figure 2.

6. A composition of claim 5 further limited by a proviso that the epitope is not an entire amino acid sequence of Figure 2.

7. A composition of claim 2 further limited by a proviso that the polypeptide is not an entire amino acid sequence of a protein of Figure 2.

8. A composition of claim 2 that comprises an antibody polypeptide epitope from an amino acid sequence of Figure 2.

9. A composition of claim 8 further limited by a proviso that the epitope is not an entire amino acid sequence of Figure 2.

10. A composition of claim 8 wherein the antibody epitope comprises a peptide region of at least 5 amino acids of Figure 2 in any whole number increment up to the end of said peptide, wherein the epitope comprises an amino acid position selected from: a) an amino acid position having a value greater than 0.5 in the Hydrophilicity profile of Figure 5, b) an amino acid position having a value less than 0.5 in the Hydropathicity profile of Figure 6; c) an amino acid position having a value greater than 0.5 in the Percent Accessible Residues profile of Figure 7; d) an amino acid position having a value greater than 0.5 in the Average Flexibility profile of Figure 8; e) an amino acid position having a value greater than 0.5 in the Beta-turn profile of Figure 9; f) a combination of at least two of a) through e); g) a combination of at least three of a) through e); h) a combination of at least four of a) through e); or WO 2004/098515 PCT/US2004/013568 305 i) a combination of five of a) through e).

11. A polynucleotide that encodes a protein of claim 1.

12. A polynucleotide of claim 11 that comprises a nucleic acid molecule set forth in Figure 2.

13. A polynucleotide of claim 12 further limited by a proviso that the encoded protein is not an entire amino acid sequence of Figure 2.

14. A composition comprising a polynucleotide that is fully complementary to a polynucleotide of claim 11.

15. An 109P1 D4 siRNA composition that comprises siRNA (double stranded RNA) that corresponds to the nucleic acid ORF sequence of the 109P1D4 protein or a subsequence thereof; wherein the subsequence is 19, 20, 21, 22, 23, 24, or 25 contiguous RNA nucleotides in length and contains sequences that are complementary and non complementary to at least a portion of the mRNA coding sequence.

16. A polynucleotide of claim 13 that further comprises an additional nucleotide sequence that encodes an additional peptide of claim 1.

17. A method of generating a mammalian immune response directed to a protein of Figure 2, the method comprising: exposing cells of the mammal's immune system to a portion of a) a 109P1 D4-related protein andior b) a nucleotide sequence that encodes said protein, whereby an immune response is generated to said protein.

18. A method of generating an immune response of claim 17, said method comprising: providing a 109P1 D4-related protein that comprises at least one T cell or at least one B cell epitope; and, contacting the epitope with a mammalian immune system T cell or B cell respectively, whereby the T cell or B cell is activated.

19. A method of claim 18 wherein the immune system cell is a B cell, whereby the activated B cell generates antibodies that specifically bind to the 109P1 D4-related protein.

20. A method of claim 18 wherein the immune system cell is a T cell that is a cytotoxic T cell (CTL), whereby the activated CTL kills an autologous cell that expresses the 109P1D4-related protein.

21. A method of claim 18 wherein the immune system cell is a T cell that is a helper T cell (HTL), whereby the activated HTL secretes cytokines that facilitate the cytotoxic activity of a cytotoxic T cell (CTL) or the antibody-producing activity of a B cell. WO 2004/098515 PCT/US2004/013568 306 corresponds to the nucleic acid ORF sequence of the 109P1 D4 protein or a subsequence thereof; wherein the subsequence is 19, 20, 21, 22, 23, 24, or 25 contiguous RNA nucleotides in length and contains sequences that are complementary and non-complementary to at least a portion of the mRNA coding sequence.

30. A composition of claim 28, further comprising a physiologically acceptable carrier.

31. A pharmaceutical composition that comprises the composition of claim 28 in a human unit dose form.

32. A composition of claim 28 wherein the substance comprises an antibody or fragment thereof that specifically binds to a protein of Figure 2.

33. An antibody or fragment thereof of claim 32, which is monoclonal.

34. An antibody of claim 32, which is a human antibody, a humanized antibody or a chimeric antibody.

35. A non-human transgenic animal that produces an antibody of claim 32.

36. A hybridoma that produces an antibody of claim 33.

37. A composition of claim 28 wherein the substance reduces or inhibits the viability, growth or reproduction status of a cell that expresses a protein of Figure 2.

38. A composition of claim 28 wherein the substance increases or enhances the viability, growth or reproduction status of a cell that expresses a protein of Figure 2.

39. A composition of claim 28 wherein the substance is selected from the group comprising: a) an antibody or fragment thereof, either of which immunospecifically binds to a protein of Figure 2; b) a polynucleotide that encodes an antibody or fragment thereof, either of which immunospecifically binds to a protein of Figure 2; c) a ribozyme that cleaves a polynucleotide having a 109P1 D4 coding sequence, or a nucleic acid molecule that encodes the ribozyme; and, a physiologically acceptable carrier; and d) human T cells, wherein said T cells specifically recognize a 109P1 D4 peptide subsequence in the context of a particular HLA molecule; e) a protein of Figure 2, or a fragment of a protein of Figure 2; f) a nucleotide encoding a protein of Figure 2, or a nucleotide encoding a fragment of a protein of Figure 2; g) a peptide of eight, nine, ten, or eleven contiguous amino acids of a protein of Figure 2; h) a peptide of Tables VIII-XXI; i) a peptide of Tables XXII to XLV; j) a peptide of Tables XLVI to XLIX; WO 2004/098515 PCT/US2004/013568 307 k) an antibody polypeptide epitope from an amino acid sequence of Figure 2; 1) a polynucleotide that encodes an antibody polypeptide epitope from an amino acid sequence of Figure 2; or m) an 109P1 D4 siRNA composition that comprises siRNA (double stranded RNA) that corresponds to the nucleic acid ORF sequence of the 109P1D4 protein or a subsequence thereof; wherein the subsequence is 19, 20, 21, 22, 23, 24, or 25 contiguous RNA nucieotides in length and contains sequences that are complementary and non-complementary to at least a portion of the mRNA coding sequence.

40. A method of inhibiting viability, growth or reproduction status of cancer cells that express a protein of Figure 2, the method comprising: administering to the cells the composition of claim 28, thereby inhibiting the viability, growth or reproduction status of said cells.

41. The method of claim 40, wherein the composition comprises an antibody or fragment thereof, either of which specifically bind to a 109P1 D4-related protein.

42. The method of claim 40, wherein the composition comprises (i) a 109P1D4-related protein or, (ii) a polynucleotide comprising a coding sequence for a 109P1 D4-related protein or comprising a polynucleotide complementary to a coding sequence for a 109P1D4-related protein.

43. The method of claim 40, wherein the composition comprises a ribozyme that cleaves a polynucleotide that encodes a protein of Figure 2.

44. The method of claim 40, wherein the composition comprises human T cells to said cancer cells, wherein said T cells specifically recognize a peptide subsequence of a protein of Figure 2 while the subsequence is in the context of the particular HLA molecule.

45. The method of claim 40, wherein the composition comprises a vector that delivers a nucleotide that encodes a single chain monoclonal antibody, whereby the encoded single chain antibody is expressed intracellularly within cancer cells that express a protein of Figure 2.

46. A method of delivering an agent to a cell that expresses a protein of Figure 2, said method comprising: providing the agent conjugated to an antibody or fragment thereof of claim 32; and, exposing the cell to the antibody-agent or fragment-agent conjugate.

47. A method of inhibiting viability, growth or reproduction status of cancer cells that express a protein of Figure 2, the method comprising: administering to the cells the composition of claim 28, thereby inhibiting the viability, growth or reproduction status of said cells.

48. A method of targeting information for preventing or treating a cancer of a tissue listed in Table I to a subject in need thereof, which comprises: WO 2004/098515 PCT/US2004/013568 308 detecting the presence or absence of the expression of a polynucleotide associated with a cancer of a tissue listed in Table I in a sample from a subject, wherein the expression of the polynucleotide is selected from the group consisting of: (a) a nucleotide sequence in Figure 2; (b) a nucleotide sequence which encodes a polypeptide encoded by a nucleotide sequence in Figure 2; (c) a nucleotide sequence which encodes a polypeptide that is 90% or more identical to the amino acid sequence encoded by a nucleotide sequence in Figure 2; directing information for preventing or treating the cancer of a tissue listed in Table I to a subject in need thereof based upon the presence or absence of the expression of the polynucleotide in the sample.

49. The method of claim 48, wherein the information comprises a description of detection procedure or treatment for a cancer of a tissue listed in Table 1.

50. A method for identifying a candidate molecule that modulates cell proliferation, which comprises: (a) introducing a test molecule to a system which comprises a nucleic acid comprising a nucleotide sequence selected from the group consisting of: (i) the nucleotide sequence of SEQ ID NO:1; (ii) a nucleotide sequence which encodes a polypeptide consisting of the amino acid sequence set forth in Figure 3; (iii) a nucleotide sequence which encodes a polypeptide that is 90% or more identical to the amino acid sequence set forth in Figure 3; and (iv) a fragment of a nucleotide sequence of (i), (ii), or (iii); or introducing a test molecule to a system which comprises a protein encoded by a nucleotide sequence of (i), (ii), (iii), or (iv); and (b) determining the presence or absence of an interaction between the test molecule and the nucleotide sequence or protein, whereby the presence of an interaction between the test molecule and the nucleotide sequence or protein identifies the test molecule as a candidate molecule that modulates cell proliferation.

51. The method of claim 50, wherein the system is an animal.

52. The method of claim 50, wherein the system is a cell.

53. The method of claim 50, wherein the test molecule comprises an antibody or antibody fragment that specifically binds the protein encoded by the nucleotide sequence of (i), (ii), (iii), or (iv).

54. A method for treating a cancer of a tissue listed in Table I in a subject, which comprises administering a candidate molecule identified by the method of claim 50 to a subject in need thereof, whereby the candidate molecule treats a cancer of a tissue listed in Table I in the subject.

55. A method for identifying a candidate therapeutic for treating a cancer of a tissue listed in Table I, which comprises: WO 2004/098515 PCT/US2004/013568 309 (a) introducing a test molecule to a system which comprises a nucleic acid comprising a nucleotide sequence selected from the group consisting of: (i) the nucleotide sequence of SEQ ID NO:1; (ii) a nucleotide sequence which encodes a polypeptide consisting of the amino acid sequence set forth in Figure 3; (iii) a nucleotide sequence which encodes a polypeptide that is 90% or more identical to the amino acid sequence set forth in Figure 3; and (iv) a fragment of a nucleotide sequence of (i), (ii), or (iii); or introducing a test molecule to a system which comprises a protein encoded by a nucleotide sequence of (i), (ii), (iii), or (iv); and (b) determining the presence or absence of an interaction between the test molecule and the nucleotide sequence or protein, whereby the presence of an interaction between the test molecule and the nucleotide sequence or protein identifies the test molecule as a candidate therapeutic for treating a cancer of a tissue listed in Table 1.

56. The method of claim 55, wherein the system is an animal.

57. The method of claim 55, wherein the system is a cell.

58. The method of claim 55, wherein the test molecule comprises an antibody or antibody fragment that specifically binds the protein encoded by the nucleoide sequence of (i), (ii), (iii), or (iv).