AU4750597A

AU4750597A - Compounds and methods for diagnosis of tuberculosis

Info

Publication number: AU4750597A
Application number: AU47505/97A
Authority: AU
Inventors: Antonio Campos-Neto; Davin C. Dillon; Raymond Houghton; Michael J. Lodes; Steven G. Reed; Yasir A.W. Skeiky; Daniel R. Twardzik; Thomas S Vedvick
Original assignee: Corixa Corp
Current assignee: Corixa Corp
Priority date: 1996-10-11
Filing date: 1997-10-07
Publication date: 1998-05-11
Also published as: NO991693L; TR199901569T2; WO1998016645A3; JP2001500383A; CA2268036A1; NO991693D0; PL333304A1; IL129389A0; BR9712298A; EP0934415A2; IL121936A0; WO1998016645A2; CZ126699A3

Description

COMPOUNDS AND METHODS FOR DIAGNOSIS OF TUBERCULOSIS

TECHNICAL FIELD

The present invention relates generally to the detection of Mycobacterium tuberculosis infection. The invention is more particularly related to polypeptides comprising a Mycobacterium tuberculosis antigen, or a portion or other variant thereof, and the use of such polypeptides for the serodiagnosis of Mycobacterium tuberculosis infection.

BACKGROUND OF THE INVENTION Tuberculosis is a chronic, infectious disease, that is generally caused by infection with Mycobacterium tuberculosis. It is a major disease in developing countries, as well as an increasing problem in developed areas of the world, with about 8 million new cases and 3 million deaths each year. Although the infection may be asymptomatic for a considerable period of time, the disease is most commonly manifested as an acute inflammation of the lungs, resulting in fever and a nonproductive cough. If left untreated, serious complications and death typically result.

Although tuberculosis can generally be controlled using extended antibiotic therapy, such treatment is not sufficient to prevent the spread of the disease. Infected individuals may be asymptomatic, but contagious, for some time. In addition, although compliance with the treatment regimen is critical, patient behavior is difficult to monitor. Some patients do not complete the course of treatment, which can lead to ineffective treatment and the development of drug resistance.

Inhibiting the spread of tuberculosis will require effective vaccination and accurate, early diagnosis of the disease. Currently, vaccination with live bacteria is the most efficient method for inducing protective immunity. The most common Mycobacterium for this purpose is Bacillus Calmette-Guerin (BCG), an avirulent strain of Mycobacterium bovis. However, the safety and efficacy of BCG is a source of controversy and some countries, such as the United States, do not vaccinate the general public. Diagnosis is commonly achieved using a skin test, which involves intradermal exposure to tuberculin PPD (protein-purified derivative). Antigen-specific T cell responses result in measurable incubation at the injection site by 48-72 hours after injection, which indicates exposure to Mycobacterial antigens. Sensitivity and specificity have, however, been a problem with this test, and individuals vaccinated with BCG cannot be distinguished from infected individuals.

While macrophages have been shown to act as the principal effectors of M. tuberculosis immunity, T cells are the predominant inducers of such immunity. The essential role of T cells in protection against M. tuberculosis infection is illustrated by the frequent occurrence of M. tuberculosis in AIDS patients, due to the depletion of CD4 T cells associated with human immunodeficiency virus (HIV) infection. Mycobacterium-reactive CD4 T cells have been shown to be potent producers of gamma-interferon (IFN-γ), which, in turn, has been shown to trigger the anti-mycobacterial effects of macrophages in mice. While the role of IFN-γ in humans is less clear, studies have shown that 1,25-dihydroxy -vitamin D3, either alone or in combination with IFN-γ or tumor necrosis factor-alpha, activates human macrophages to inhibit M. tuberculosis infection. Furthermore, it is known that IFN-γ stimulates human macrophages to make 1 ,25-dihydroxy-vitamin D3. Similarly, IL-12 has been shown to play a role in stimulating resistance to M. tuberculosis infection. For a review of the immunology of M. tuberculosis infection see Chan and Kaufmann, in Tuberculosis: Pathogenesis, Protection and Control, Bloom (ed.), ASM Press, Washington, DC, 1994.

Accordingly, there is a need in the art for improved diagnostic methods for detecting tuberculosis. The present invention fulfills this need and further provides other related advantages.

SUMMARY OF THE INVENTION

Briefly stated, the present invention provides compositions and methods for diagnosing tuberculosis. In one aspect, polypeptides are provided comprising an antigenic portion of a soluble M. tuberculosis antigen, or a variant of such an antigen that differs only in conservative substitutions and/or modifications. In one embodiment of this aspect, the soluble antigen has one of the following N-terminal sequences:

(a) Asp-Pro- Val- Asp-Ala- Val-Ile-Asn-Thr-Thr-Cys-Asn-Tyr-Gly-Gln- Val-Val-Ala- Ala-Leu (SEQ ID NO: 115); (b) Ala-Val-Glu-Ser-Gly-Met-Leu-Ala-Leu-Gly-Thr-Pro-Ala-Pro-Ser (SEQ ID NO: 116);

(c) Ala-Ala-Met-Lys-Pro-Arg-Thr-Gly-Asp-Gly-Pro-Leu-Glu-Ala-Ala- Lys-Glu-Gly-Arg (SEQ ID NO: 117); (d) Tyr-Tyr-Trp-Cys-Pro-Gly-Gln-Pro-Phe-Asp-Pro-Ala-Trp-Gly-Pro

(SEQ ID NO: 118);

(e) Asp-Ile-Gly-Ser-Glu-Ser-Thr-Glu-Asp-Gln-Gln-Xaa-Ala-Val (SEQ ID NO: 119);

(f) Ala-Glu-Glu-Ser-Ile-Ser-Thr-Xaa-Glu-Xaa-Ile-Val-Pro (SEQ ID NO: 120);

(g) Asp-Pro-Glu-Pro-Ala-Pro-Pro-Val-Pro-Thr-Thr-Ala-Ala-Ser-Pro-Pro- Ser (SEQ ID NO: 121);

(h) Ala-Pro-Lys-Thr-Tyr-Xaa-Glu-Glu-Leu-Lys-Gly-Thr-Asp-Thr-Gly

(SEQ ID NO: 122); (i) Asp-Pro-Ala-Ser-Ala-Pro-Asp-Val-Pro-Thr-Ala-Ala-Gln-Leu-Thr-Ser-

Leu-Leu-Asn-Ser-Leu-Ala-Asp-Pro-Asn-Val-Ser-Phe-Ala-Asn (SEQ

ID NO: 123); (j) Xaa-Asp-Ser-Glu-Lys-Ser-Ala-Thr-Ile-Lys-Val-Thr-Asp-Ala-Ser;

(SEQ ID NO: 129) (k) Ala-Gly-Asp-Thr-Xaa-Ile-Tyr-Ile-Val-Gly-Asn-Leu-Thr-Ala-Asp;

(SEQ ID NO: 130) or (1) Ala-Pro-Glu-Ser-Gly-Ala-Gly-Leu-Gly-Gly-Thr-Val-Gln-Ala-Gly;

(SEQ ID NO: 131)

wherein Xaa may be any amino acid.

In a related aspect, polypeptides are provided comprising an immunogenic portion of an M. tuberculosis antigen, or a variant of such an antigen that differs only in conservative substitutions and/or modifications, the antigen having one of the following N- terminal sequences: (m) Xaa-Tyr-Ile-Ala-Tyr-Xaa-Thr-Thr-Ala-Gly-Ile-Val-Pro-Gly-Lys-Ile-

Asn-Val-His-Leu-Val; (SEQ ID NO: 132) or (n) Asp-Pro-Pro-Asp-Pro-His-Gln-Xaa-Asp-Met-Thr-Lys-Gly-Tyr-Tyr- Pro-Gly-Gly-Arg-Arg-Xaa-Phe; (SEQ ID NO: 124) wherein Xaa may be any amino acid.

In another embodiment, the soluble M. tuberculosis antigen comprises an amino acid sequence encoded by a DNA sequence selected from the group consisting of the sequences recited in SEQ ID NOS: 1, 2, 4-10, 13-25, 52, 94 and 96, the complements of said sequences, and DNA sequences that hybridize to a sequence recited in SEQ ID NOS: 1, 2, 4-10, 13-25, 52, 94 and 96 or a complement thereof under moderately stringent conditions.

In a related aspect, the polypeptides comprise an antigenic portion of a M. tuberculosis antigen, or a variant of such an antigen that differs only in conservative substitutions and/or modifications, wherein the antigen comprises an amino acid sequence encoded by a DNA sequence selected from the group consisting of the sequences recited in SEQ ID NOS: 26-51, 133, 134, 158-178 and 196, the complements of said sequences, and DNA sequences that hybridize to a sequence recited in SEQ ID NOS: 26-51, 133, 134, 158- 178 and 196 or a complement thereof under moderately stringent conditions.

In related aspects, DNA sequences encoding the above polypeptides, recombinant expression vectors comprising these DNA sequences and host cells transformed or transfected with such expression vectors are also provided.

In another aspect, the present invention provides fusion proteins comprising a first and a second inventive polypeptide or, alternatively, an inventive polypeptide and a known M. tuberculosis antigen.

In further aspects of the subject invention, methods and diagnostic kits are provided for detecting tuberculosis in a patient. The methods comprise: (a) contacting a biological sample with at least one of the above polypeptides; and (b) detecting in the sample the presence of antibodies that bind to the polypeptide or polypeptides, thereby detecting M. tuberculosis infection in the biological sample. Suitable biological samples include whole blood, sputum, serum, plasma, saliva, cerebrospinal fluid and urine. The diagnostic kits comprise one or more of the above polypeptides in combination with a detection reagent. The present invention also provides methods for detecting M. tuberculosis infection comprising: (a) obtaining a biological sample from a patient; (b) contacting the sample with at least one oligonucleotide primer in a polymerase chain reaction, the oligonucleotide primer being specific for a DNA sequence encoding the above polypeptides; and (c) detecting in the sample a DNA sequence that amplifies in the presence of the first and second oligonucleotide primers. In one embodiment, the oligonucleotide primer comprises at least about 10 contiguous nucleotides of such a DNA sequence.

In a further aspect, the present invention provides a method for detecting M. tuberculosis infection in a patient comprising: (a) obtaining a biological sample from the patient; (b) contacting the sample with an oligonucleotide probe specific for a DNA sequence encoding the above polypeptides; and (c) detecting in the sample a DNA sequence that hybridizes to the oligonucleotide probe. In one embodiment, the oligonucleotide probe comprises at least about 15 contiguous nucleotides of such a DNA sequence.

In yet another aspect, the present invention provides antibodies, both polyclonal and monoclonal, that bind to the polypeptides described above, as well as methods for their use in the detection of M. tuberculosis infection.

These and other aspects of the present invention will become apparent upon reference to the following detailed description and attached drawings. All references disclosed herein are hereby incorporated by reference in their entirety as if each was incorporated individually.

BRIEF DESCRIPTION OF THE DRAWINGS AND SEQUENCE IDENTIFIERS

Figure 1A and B illustrate the stimulation of proliferation and interferon-γ production in T cells derived from a first and a second M. tuberculosis-immune donor, respectively, by the 14 Kd, 20 Kd and 26 Kd antigens described in Example 1.

Figures 2A-D illustrate the reactivity of antisera raised against secretory M. tuberculosis proteins, the known M. tuberculosis antigen 85b and the inventive antigens

Tb38-1 and TbH-9, respectively, with M. tuberculosis lysate (lane 2), M. tuberculosis secretory proteins (lane 3), recombinant Tb38-1 (lane 4), recombinant TbH-9 (lane 5) and recombinant 85b (lane 5). Figure 3 A illustrates the stimulation of proliferation in a TbH-9-specific T cell clone by secretory M. tuberculosis proteins, recombinant TbH-9 and a control antigen, TbRal l.

Figure 3B illustrates the stimulation of interferon-γ production in a TbH-9- specific T cell clone by secretory M. tuberculosis proteins, PPD and recombinant TbH-9.

Figure 4 illustrates the reactivity of two representative polypeptides with sera from M. tuberculosis-infected and uninfected individuals, as compared to the reactivity of bacterial lysate.

Figure 5 shows the reactivity of four representative polypeptides with sera from M. tuberculosis-infected and uninfected individuals, as compared to the reactivity of the 38 kD antigen.

Figure 6 shows the reactivity of recombinant 38 kD and TbRal 1 antigens with sera from M. tuberculosis patients, PPD positive donors and normal donors.

Figure 7 shows the reactivity of the antigen TbRa2A with 38 kD negative sera. Figure 8 shows the reactivity of the antigen of SEQ ID NO: 60 with sera from

M. tuberculosis patients and normal donors.

Figure 9 illustrates the reactivity of the recombinant antigen TbH-29 (SEQ ID NO: 137) with sera from M. tuberculosis patients, PPD positive donors and normal donors as determined by indirect ELISA. Figure 10 illustrates the reactivity of the recombinant antigen TbH-33 (SEQ

ID NO: 140) with sera from M. tuberculosis patients and from normal donors, and with a pool of sera from M. tuberculosis patients, as determined both by direct and indirect ELISA

Figure 11 illustrates the reactivity of increasing concentrations of the recombinant antigen TbH-33 (SEQ ID NO: 140) with sera from M. tuberculosis patients and from normal donors as determined by ELISA.

SEQ. ID NO. 1 is the DNA sequence of TbRal. SEQ. ID NO. 2 is the DNA sequence of TbRal 0. SEQ. ID NO. 3 is the DNA sequence of TbRal 1. SEQ. ID NO. 4 is the DNA sequence of TbRal 2. SEQ. ID NO. 5 is the DNA sequence of TbRal 3. SEQ. ID NO. 6 is the DNA sequence of TbRal 6. SEQ. ID NO. 7 is the DNA sequence of TbRal 7. SEQ. ID NO. 8 is the DNA sequence of TbRal 8. SEQ. ID NO. 9 is the DNA sequence of TbRal 9. SEQ. ID NO. 10 is the DNA sequence of TbRa24. SEQ. ID NO. 11 is the DNA sequence of TbRa26. SEQ. ID NO. 12 is the DNA sequence of TbRa28. SEQ. ID NO. 13 is the DNA sequence of TbRa29. SEQ. ID NO. 14 is the DNA sequence of TbRa2A. SEQ. ID NO. 15 is the DNA sequence of TbRa3. SEQ. ID NO. 16 is the DNA sequence of TbRa32. SEQ. ID NO. 17 is the DNA sequence of TbRa35. SEQ. ID NO. 18 is the DNA sequence of TbRa36. SEQ. ID NO. 19 is the DNA sequence of TbRa4. SEQ. ID NO. 20 is the DNA sequence of TbRa9. SEQ. ID NO. 21 is the DNA sequence of TbRaB. SEQ. ID NO. 22 is the DNA sequence of TbRaC. SEQ. ID NO. 23 is the DNA sequence of TbRaD. SEQ. ID NO. 24 is the DNA sequence of YYWCPG. SEQ. ID NO. 25 is the DNA sequence of AAMK. SEQ. ID NO. 26 is the DNA sequence of TbL-23. SEQ. ID NO. 27 is the DNA sequence of TbL-24. SEQ. ID NO. 28 is the DNA sequence of TbL-25. SEQ. ID NO. 29 is the DNA sequence of TbL-28. SEQ. ID NO. 30 is the DNA sequence of TbL-29. SEQ. ID NO. 31 is the DNA sequence of TbH-5. SEQ. ID NO. 32 is the DNA sequence of TbH-8. SEQ. ID NO. 33 is the DNA sequence of TbH-9. SEQ. ID NO. 34 is the DNA sequence of TbM-1. SEQ. ID NO. 35 is the DNA sequence of TbM-3. SEQ. ID NO. 36 is the DNA sequence of TbM-6. SEQ. ID NO. 37 is the DNA sequence of TbM-7. SEQ. ID NO. 38 is the DNA sequence of TbM-9. SEQ. ID NO. 39 is the DNA sequence of TbM-12. SEQ. ID NO. 40 is the DNA sequence of TbM-13. SEQ. ID NO. 41 is the DNA sequence of TbM-14. SEQ. ID NO. 42 is the DNA sequence of TbM-15. SEQ. ID NO. 43 is the DNA sequence of TbH-4. SEQ. ID NO. 44 is the DNA sequence of TbH-4-FWD. SEQ. ID NO. 45 is the DNA sequence of TbH-12. SEQ. ID NO. 46 is the DNA sequence of Tb38-1. SEQ. ID NO. 47 is the DNA sequence of Tb38-4. SEQ. ID NO. 48 is the DNA sequence of TbL-17. SEQ. ID NO. 49 is the DNA sequence of TbL-20. SEQ. ID NO. 50 is the DNA sequence of TbL-21. SEQ. ID NO. 51 is the DNA sequence of TbH-16. SEQ. ID NO. 52 is the DNA sequence of DPEP. SEQ. ID NO. 53 is the deduced amino acid sequence of DPEP. SEQ. ID NO. 54 is the protein sequence of DPV N-terminal Antigen. SEQ. ID NO. 55 is the protein sequence of AVGS N-terminal Antigen. SEQ. ID NO. 56 is the protein sequence of AAMK N-terminal Antigen. SEQ. ID NO. 57 is the protein sequence of YYWC N-terminal Antigen. SEQ. ID NO. 58 is the protein sequence of DIGS N-terminal Antigen. SEQ. ID NO. 59 is the protein sequence of AEES N-terminal Antigen. SEQ. ID NO. 60 is the protein sequence of DPEP N-terminal Antigen. SEQ. ID NO. 61 is the protein sequence of APKT N-terminal Antigen. SEQ. ID NO. 62 is the protein sequence of DPAS N-terminal Antigen. SEQ. ID NO. 63 is the deduced amino acid sequence of TbM-1 Peptide. SEQ. ID NO. 64 is the deduced amino acid sequence of TbRal . SEQ. ID NO. 65 is the deduced amino acid sequence of TbRal 0. SEQ. ID NO. 66 is the deduced amino acid sequence of TbRal 1. SEQ. ID NO. 67 is the deduced amino acid sequence of TbRal 2. SEQ. ID NO. 68 is the deduced amino acid sequence of TbRal 3. SEQ. ID NO. 69 is the deduced amino acid sequence of TbRal 6. SEQ. ID NO. 70 is the deduced amino acid sequence of TbRal 7. SEQ. ID NO. 71 is the deduced amino acid sequence of TbRal 8. SEQ. ID NO. 72 is the deduced amino acid sequence of TbRal 9. SEQ. ID NO. 73 is the deduced amino acid sequence of TbRa24. SEQ. ID NO. 74 is the deduced amino acid sequence of TbRa26. SEQ. ID NO. 75 is the deduced amino acid sequence of TbRa28. SEQ. ID NO. 76 is the deduced amino acid sequence of TbRa29. SEQ. ID NO. 77 is the deduced amino acid sequence of TbRa2A. SEQ. ID NO. 78 is the deduced amino acid sequence of TbRa3. SEQ. ID NO. 79 is the deduced amino acid sequence of TbRa32. SEQ. ID NO. 80 is the deduced amino acid sequence of TbRa35. SEQ. ID NO. 81 is the deduced amino acid sequence of TbRa36. SEQ. ID NO. 82 is the deduced amino acid sequence of TbRa4. SEQ. ID NO. 83 is the deduced amino acid sequence of TbRa9. SEQ. ID NO. 84 is the deduced amino acid sequence of TbRaB. SEQ. ID NO. 85 is the deduced amino acid sequence of TbRaC. SEQ. ID NO. 86 is the deduced amino acid sequence of TbRaD. SEQ. ID NO. 87 is the deduced amino acid sequence of YYWCPG. SEQ. ID NO. 88 is the deduced amino acid sequence of TbAAMK. SEQ. ID NO. 89 is the deduced amino acid sequence of Tb38-1. SEQ. ID NO. 90 is the deduced amino acid sequence of TbH-4. SEQ. ID NO. 91 is the deduced amino acid sequence of TbH-8. SEQ. ID NO. 92 is the deduced amino acid sequence of TbH-9. SEQ. ID NO. 93 is the deduced amino acid sequence of TbH-12. SEQ. ID NO. 94 is the DNA sequence of DPAS. SEQ. ID NO. 95 is the deduced amino acid sequence of DPAS.

SEQ. ID NO. 96 is the DNA sequence of DPV.

SEQ. ID NO. 97 is the deduced amino acid sequence of DPV.

SEQ. ID NO. 98 is the DNA sequence of ESAT-6.

SEQ. ID NO. 99 is the deduced amino acid sequence of ESAT-6.

SEQ. ID NO. 100 is the DNA sequence of TbH-8-2.

SEQ. ID NO. 101 is the DNA sequence of TbH-9FL.

SEQ. ID NO. 102 is the deduced amino acid sequence of TbH-9FL.

SEQ. ID NO. 103 is the DNA sequence of TbH-9- 1.

SEQ. ID NO. 104 is the deduced amino acid sequence of TbH-9- 1.

SEQ. ID NO. 105 is the DNA sequence of TbH-9-4.

SEQ. ID NO. 106 is the deduced amino acid sequence of TbH-9-4.

SEQ. ID NO. 107 is the DNA sequence of Tb38-1F2 IN.

SEQ. ID NO. 108 is the DNA sequence of Tb38-1F2 RP.

SEQ. ID NO. 109 is the deduced amino acid sequence of Tb37-FL.

SEQ. ID NO. 110 is the deduced amino acid sequence of Tb38-IN.

SEQ. ID NO. 111 is the DNA sequence of Tb38-1F3.

SEQ. ID NO. 112 is the deduced amino acid sequence of Tb38-1F3.

SEQ. ID NO. 113 is the DNA sequence of Tb38-1F5.

SEQ. ID NO. 114 is the DNA sequence of Tb38-1F6.

SEQ. ID NO. 115 is the deduced N-terminal amino acid sequence of DPV.

SEQ. ID NO. 116 is the deduced N-terminal amino acid sequence of AVGS.

SEQ. ID NO. 117 is the deduced N-terminal amino acid sequence of AAMK.

SEQ. ID NO. 118 is the deduced N-terminal amino acid sequence of YYWC.

SEQ. ID NO. 119 is the deduced N-terminal amino acid sequence of DIGS.

SEQ. ID NO. 120 is the deduced N-terminal amino acid sequence of AAES.

SEQ. ID NO. 121 is the deduced N-terminal amino acid sequence of DPEP.

SEQ. ID NO. 122 is the deduced N-terminal amino acid sequence of APKT.

SEQ. ID NO. 123 is the deduced N-terminal amino acid sequence of DPAS.

SEQ. ID NO. 124 is the protein sequence of DPPD N-terminal Antigen. SEQ ID NO. 125-128 are the protein sequences of four DPPD cyanogen bromide fragments.

SEQ ID NO. 129 is the N-terminal protein sequence of XDS antigen.

SEQ ID NO. 130 is the N-terminal protein sequence of AGD antigen. SEQ ID NO. 131 is the N-terminal protein sequence of APE antigen.

SEQ ID NO. 132 is the N-terminal protein sequence of XYI antigen.

SEQ ID NO. 133 is the DNA sequence of TbH-29.

SEQ ID NO. 134 is the DNA sequence of TbH-30.

SEQ ID NO. 135 is the DNA sequence of TbH-32. SEQ ID NO. 136 is the DNA sequence of TbH-33.

SEQ ID NO. 137 is the predicted amino acid sequence of TbH-29.

SEQ ID NO. 138 is the predicted amino acid sequence of TbH-30.

SEQ ID NO. 139 is the predicted amino acid sequence of TbH-32.

SEQ ID NO. 140 is the predicted amino acid sequence of TbH-33. SEQ ID NO: 141-146 are PCR primers used in the preparation of a fusion protein containing TbRa3, 38 kD and Tb38-1.

SEQ ID NO: 147 is the DNA sequence of the fusion protein containing TbRa3, 38 kD and Tb38-l.

SEQ ID NO: 148 is the amino acid sequence of the fusion protein containing TbRa3, 38 kD and Tb38-l .

SEQ ID NO: 149 is the DNA sequence of the M. tuberculosis antigen 38 kD.

SEQ ID NO: 150 is the amino acid sequence of the M. tuberculosis antigen 38 kD.

SEQ ID NO: 151 is the DNA sequence of XP14.

SEQ ID NO: 152 is the DNA sequence of XP24. SEQ ID NO: 153 is the DNA sequence of XP31.

SEQ ID NO: 154 is the 5' DNA sequence of XP32.

SEQ ID NO: 155 is the 3' DNA sequence of XP32.

SEQ ID NO: 156 is the predicted amino acid sequence of XP14.

SEQ ID NO: 157 is the predicted amino acid sequence encoded by the reverse complement of XP 14. the DNA sequence of XP27. the DNA sequence of XP36. the 5' DNA sequence of XP4. the 5' DNA sequence of XP5. the 5' DNA sequence of XP17. the 5' DNA sequence of XP30. the 5' DNA sequence of XP2. the 3' DNA sequence of XP2. the 5' DNA sequence of XP3. the 3' DNA sequence of XP3. the 5' DNA sequence of XP6. the 3' DNA sequence of XP6. the 5' DNA sequence of XP18. the 3' DNA sequence of XP18. the 5' DNA sequence of XP19. the 3' DNA sequence of XP19. the 5' DNA sequence of XP22. the 3' DNA sequence of XP22. the 5' DNA sequence of XP25. the 3' DNA sequence of XP25. the full-length DNA sequence of TbH4-XPl. the predicted amino acid sequence of TbH4-XPl. SEQ ID NO: 180 is the predicted amino acid sequence encoded by the reverse complement of TbH4-XPl.

SEQ ID NO: 181 is a first predicted amino acid sequence encoded by XP36. SEQ ID NO: 182 is a second predicted amino acid sequence encoded by XP36. SEQ ID NO: 183 is the predicted amino acid sequence encoded by the reverse complement of XP36.

SEQ ID NO: 184 is the DNA sequence of RDIF2. SEQ ID NO: 185 is the DNA sequence of RDIF5. SEQ ID NO: 186 is the DNA sequence of RDIF8.

SEQ ID NO: 187 is the DNA sequence of RDIF10.

SEQ ID NO: 188 is the DNA sequence of RDIF11.

SEQ ID NO: 189 is the predicted amino acid sequence of RDIF2.

SEQ ID NO: 190 is the predicted amino acid sequence of RDIF5.

SEQ ID NO: 191 is the predicted amino acid sequence of RDIF8.

SEQ ID NO: 192 is the predicted amino acid sequence of RDIF10.

SEQ ID NO: 193 is the predicted amino acid sequence of RDIF 11.

SEQ ID NO: 194 is the 5' DNA sequence of RDIF 12.

SEQ ID NO: 195 is the 3' DNA sequence of RDIF 12.

SEQ ID NO: 196 is the DNA sequence of RDIF7.

SEQ ID NO: 197 is the predicted amino acid sequence of RDIF7.

SEQ ID NO: 198 is the DNA sequence of DIF2-1.

SEQ ID NO: 199 is the predicted amino acid sequence of DIF2-1.

SEQ ID NO: 200-207 are PCR primers used in the preparation of a fusion prote: containing TbRa3, 38 kD, Tb38-1 and DPEP (hereinafter referred to as TbF-2).

SEQ ID NO: 208 is the DNA sequence of the fusion protein TbF-2.

SEQ ID NO: 209 is the amino acid sequence of the fusion protein TbF-2.

DETAILED DESCRIPTION OF THE INVENTION

As noted above, the present invention is generally directed to compositions and methods for diagnosing tuberculosis. The compositions of the subject invention include polypeptides that comprise at least one antigenic portion of a M. tuberculosis antigen, or a variant of such an antigen that differs only in conservative substitutions and/or modifications. Polypeptides within the scope of the present invention include, but are not limited to, soluble M. tuberculosis antigens. A "soluble M. tuberculosis antigen" is a protein of M. tuberculosis origin that is present in M. tuberculosis culture filtrate. As used herein, the term "polypeptide" encompasses amino acid chains of any length, including full length proteins (i.e., antigens), wherein the amino acid residues are linked by covalent peptide bonds. Thus, a polypeptide comprising an antigenic portion of one of the above antigens may consist entirely of the antigenic portion, or may contain additional sequences. The additional sequences may be derived from the native M. tuberculosis antigen or may be heterologous, and such sequences may (but need not) be antigenic. An "antigenic portion" of an antigen (which may or may not be soluble) is a portion that is capable of reacting with sera obtained from an M. tuberculosis-infected individual (i. e. , generates an absorbance reading with sera from infected individuals that is at least three standard deviations above the absorbance obtained with sera from uninfected individuals, in a representative ELISA assay described herein). An "M tuberculosis-infected individual" is a human who has been infected with M. tuberculosis (e.g., has an intradermal skin test response to PPD that is at least 0.5 cm in diameter). Infected individuals may display symptoms of tuberculosis or may be free of disease symptoms. Polypeptides comprising at least an antigenic portion of one or more M. tuberculosis antigens as described herein may generally be used, alone or in combination, to detect tuberculosis in a patient. The compositions and methods of this invention also encompass variants of the above polypeptides. A "variant," as used herein, is a polypeptide that differs from the native antigen only in conservative substitutions and/or modifications, such that the antigenic properties of the polypeptide are retained. Such variants may generally be identified by modifying one of the above polypeptide sequences, and evaluating the antigenic properties of the modified polypeptide using, for example, the representative procedures described herein.

A "conservative substitution" is one in which an amino acid is substituted for another amino acid that has similar properties, such that one skilled in the art of peptide chemistry would expect the secondary structure and hydropathic nature of the polypeptide to be substantially unchanged. In general, the following groups of amino acids represent conservative changes: (1) ala, pro, gly, glu, asp, gin, asn, ser, thr; (2) cys, ser, tyr, thr; (3) val, ile, leu, met, ala, phe; (4) lys, arg, his; and (5) phe, tyr, trp, his.

Variants may also (or alternatively) be modified by, for example, the deletion or addition of amino acids that have minimal influence on the antigenic properties, secondary structure and hydropathic nature of the polypeptide. For example, a polypeptide may be conjugated to a signal (or leader) sequence at the N-terminal end of the protein which co- translationally or post-translationally directs transfer of the protein. The polypeptide may also be conjugated to a linker or other sequence for ease of synthesis, purification or identification of the polypeptide (e.g., poly-His), or to enhance binding of the polypeptide to a solid support. For example, a polypeptide may be conjugated to an immunoglobulin Fc region.

In a related aspect, combination polypeptides are disclosed. A "combination polypeptide" is a polypeptide comprising at least one of the above antigenic portions and one or more additional antigenic M. tuberculosis sequences, which are joined via a peptide linkage into a single amino acid chain. The sequences may be joined directly (i.e., with no intervening amino acids) or may be joined by way of a linker sequence (e.g., Gly-Cys-Gly) that does not significantly diminish the antigenic properties of the component polypeptides.

In general, M. tuberculosis antigens, and DNA sequences encoding such antigens, may be prepared using any of a variety of procedures. For example, soluble antigens may be isolated from M. tuberculosis culture filtrate by procedures known to those of ordinary skill in the art, including anion-exchange and reverse phase chromatography. Purified antigens may then be evaluated for a desired property, such as the ability to react with sera obtained from an M. tuberculosis-infected individual. Such screens may be performed using the representative methods described herein. Antigens may then be partially sequenced using, for example, traditional Edman chemistry. See Edman and Berg, Eur. J. Biochem. 50: 116-132, 1967.

Antigens may also be produced recombinantly using a DNA sequence that encodes the antigen, which has been inserted into an expression vector and expressed in an appropriate host. DNA molecules encoding soluble antigens may be isolated by screening an appropriate M. tuberculosis expression library with anti-sera (e.g., rabbit) raised specifically against soluble M. tuberculosis antigens. DNA sequences encoding antigens that may or may not be soluble may be identified by screening an appropriate M. tuberculosis genomic or cDNA expression library with sera obtained from patients infected with M. tuberculosis. Such screens may generally be performed using techniques well known in the art, such as those described in Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratories, Cold Spring Harbor, NY, 1989. DNA sequences encoding soluble antigens may also be obtained by screening an appropriate M. tuberculosis cDNA or genomic DNA library for DNA sequences that hybridize to degenerate oligonucleotides derived from partial amino acid sequences of isolated soluble antigens. Degenerate oligonucleotide sequences for use in such a screen may be designed and synthesized, and the screen may be performed, as described (for example) in Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratories, Cold Spring Harbor, NY (and references cited therein). Polymerase chain reaction (PCR) may also be employed, using the above oligonucleotides in methods well known in the art, to isolate a nucleic acid probe from a cDNA or genomic library. The library screen may then be performed using the isolated probe.

Regardless of the method of preparation, the antigens described herein are "antigenic." More specifically, the antigens have the ability to react with sera obtained from an M. tuberculosis-infected individual. Reactivity may be evaluated using, for example, the representative ELISA assays described herein, where an absorbance reading with sera from infected individuals that is at least three standard deviations above the absorbance obtained with sera from uninfected individuals is considered positive.

Antigenic portions of M. tuberculosis antigens may be prepared and identified using well known techniques, such as those summarized in Paul, Fundamental Immunology, 3d ed., Raven Press, 1993, pp. 243-247 and references cited therein. Such techniques include screening polypeptide portions of the native antigen for antigenic properties. The representative ELISAs described herein may generally be employed in these screens. An antigenic portion of a polypeptide is a portion that, within such representative assays, generates a signal in such assays that is substantially similar to that generated by the full length antigen. In other words, an antigenic portion of a M. tuberculosis antigen generates at least about 20%>, and preferably about 100%, of the signal induced by the full length antigen in a model ELISA as described herein.

Portions and other variants of M. tuberculosis antigens may be generated by synthetic or recombinant means. Synthetic polypeptides having fewer than about 100 amino acids, and generally fewer than about 50 amino acids, may be generated using techniques well known in the art. For example, such polypeptides may be synthesized using any of the commercially available solid-phase techniques, such as the Merrifield solid-phase synthesis method, where amino acids are sequentially added to a growing amino acid chain. See Merrifield, J. Am. Chem. Soc. 55:2149-2146, 1963. Equipment for automated synthesis of polypeptides is commercially available from suppliers such as Applied BioSystems, Inc., Foster City, CA, and may be operated according to the manufacturer's instructions. Variants of a native antigen may generally be prepared using standard mutagenesis techniques, such as oligonucleotide-directed site-specific mutagenesis. Sections of the DNA sequence may also be removed using standard techniques to permit preparation of truncated polypeptides.

Recombinant polypeptides containing portions and/or variants of a native antigen may be readily prepared from a DNA sequence encoding the polypeptide using a variety of techniques well known to those of ordinary skill in the art. For example, supernatants from suitable host/vector systems which secrete recombinant protein into culture media may be first concentrated using a commercially available filter. Following concentration, the concentrate may be applied to a suitable purification matrix such as an affinity matrix or an ion exchange resin. Finally, one or more reverse phase HPLC steps can be employed to further purify a recombinant protein.

Any of a variety of expression vectors known to those of ordinary skill in the art may be employed to express recombinant polypeptides as described herein. Expression may be achieved in any appropriate host cell that has been transformed or transfected with an expression vector containing a DNA molecule that encodes a recombinant polypeptide. Suitable host cells include prokaryotes, yeast and higher eukaryotic cells. Preferably, the host cells employed are E. coli, yeast or a mammalian cell line, such as COS or CHO. The DNA sequences expressed in this manner may encode naturally occurring antigens, portions of naturally occurring antigens, or other variants thereof. In general, regardless of the method of preparation, the polypeptides disclosed herein are prepared in substantially pure form. Preferably, the polypeptides are at least about 80% pure, more preferably at least about 90% pure and most preferably at least about 99% pure. For use in the methods described herein, however, such substantially pure polypeptides may be combined. In certain specific embodiments, the subject invention discloses polypeptides comprising at least an antigenic portion of a soluble M. tuberculosis antigen (or a variant of such an antigen), where the antigen has one of the following N-terminal sequences:

(a) Asp-Pro- Val-Asp-Ala-Val-Ile-Asn-Thr-Thr-Cys-Asn-Tyr-Gly-Gln- Val- Val- Ala- Ala-Leu (SEQ ID NO: 115);

(b) Ala-Val-Glu-Ser-Gly-Met-Leu-Ala-Leu-Gly-Thr-Pro-Ala-Pro-Ser (SEQ ID NO: 116);

(c) Ala-Ala-Met-Lys-Pro-Arg-Thr-Gly-Asp-Gly-Pro-Leu-Glu-Ala-Ala- Lys-Glu-Gly-Arg (SEQ ID NO: 117); (d) Tyr-Tyr-Trp-Cys-Pro-Gly-Gln-Pro-Phe- Asp-Pro- Ala-Trp-Gly-Pro

(SEQ ID NO: 1 18);

(e) Asp-Ile-Gly-Ser-Glu-Ser-Thr-Glu-Asp-Gln-Gln-Xaa-Ala-Val (SEQ ID NO: 119);

(f) Ala-Glu-Glu-Ser-Ile-Ser-Thr-Xaa-Glu-Xaa-Ile-Val-Pro (SEQ ID NO: 120);

(h) Ala-Pro-Lys-Thr-Tyr-Xaa-Glu-Glu-Leu-Lys-Gly-Thr-Asp-Thr-Gly (SEQ ID NO: 122); (i) Asp-Pro-Ala-Ser-Ala-Pro-Asp-Val-Pro-Thr-Ala-Ala-Gln-Gln-Thr-Ser-

Leu-Leu-Asn-Ser-Leu-Ala-Asp-Pro-Asn-Val-Ser-Phe-Ala-Asn (SEQ ID NO: 123); (j) Xaa-Asp-Ser-Glu-Lys-Ser-Ala-Thr-Ile-Lys-Val-Thr-Asp-Ala-Ser; (SEQ ID NO: 129) (k) Ala-Gly-Asp-Thr-Xaa-Ile-Tyr-Ile-Val-Gly-Asn-Leu-Thr-Ala-Asp;

(SEQ ID NO: 130) or (1) Ala-Pro-Glu-Ser-Gly-Ala-Gly-Leu-Gly-Gly-Thr-Val-Gln-Ala-Gly; (SEQ ID NO: 131) wherein Xaa may be any amino acid, preferably a cysteine residue. A DNA sequence encoding the antigen identified as (g) above is provided in SEQ ID NO: 52, the deduced amino acid sequence of which is provided in SEQ ID NO: 53. A DNA sequence encoding the antigen identified as (a) above is provided in SEQ ID NO: 96; its deduced amino acid sequence is provided in SEQ ID NO: 97. A DNA sequence corresponding to antigen (d) above is provided in SEQ ID NO: 24, a DNA sequence corresponding to antigen (c) is provided in SEQ ID NO: 25 and a DNA sequence corresponding to antigen (I) is disclosed in SEQ ID NO: 94 and its deduced amino acid sequence is provided in SEQ ID NO: 95.

In a further specific embodiment, the subject invention discloses polypeptides comprising at least an immunogenic portion of an M. tuberculosis antigen having one of the following N-terminal sequences, or a variant thereof that differs only in conservative substitutions and/or modifications:

(m) Xaa-Tyr-Ile-Ala-Tyr-Xaa-Thr-Thr-Ala-Gly-Ile-Val-Pro-Gly-Lys-Ile- Asn-Val-His-Leu-Val; (SEQ ID NO: 132) or

(n) Asp-Pro-Pro- Asp-Pro-His-Gln-Xaa-Asp-Met-Thr-Lys-Gly-Tyr-Tyr- Pro-Gly-Gly-Arg- Arg-Xaa-Phe; (SEQ ID NO : 124) wherein Xaa may be any amino acid, preferably a cysteine residue.

In other specific embodiments, the subject invention discloses polypeptides comprising at least an antigenic portion of a soluble M. tuberculosis antigen (or a variant of such an antigen) that comprises one or more of the amino acid sequences encoded by (a) the DNA sequences of SEQ ID NOS: 1, 2, 4-10, 13-25, 52, 94 and 96, (b) the complements of such DNA sequences, or (c) DNA sequences substantially homologous to a sequence in (a) or (b).

In further specific embodiments, the subject invention discloses polypeptides comprising at least an antigenic portion of a M. tuberculosis antigen (or a variant of such an antigen), which may or may not be soluble, that comprises one or more of the amino acid sequences encoded by (a) the DNA sequences of SEQ ID NOS: 26-51, 133, 134, 158-178 and 196, (b) the complements of such DNA sequences or (c) DNA sequences substantially homologous to a sequence in (a) or (b).

In the specific embodiments discussed above, the M. tuberculosis antigens include variants that are encoded DNA sequences which are substantially homologous to one or more of DNA sequences specifically recited herein. "Substantial homology," as used herein, refers to DNA sequences that are capable of hybridizing under moderately stringent conditions. Suitable moderately stringent conditions include prewashing in a solution of 5X SSC, 0.5% SDS, 1.0 mM EDTA (pH 8.0); hybridizing at 50°C-65°C, 5X SSC, overnight or, in the event of cross-species homology, at 45°C with 0.5X SSC; followed by washing twice at 65°C for 20 minutes with each of 2X, 0.5X and 0.2X SSC containing 0.1% SDS). Such hybridizing DNA sequences are also within the scope of this invention, as are nucleotide sequences that, due to code degeneracy, encode an immunogenic polypeptide that is encoded by a hybridizing DNA sequence. In a related aspect, the present invention provides fusion proteins comprising a first and a second inventive polypeptide or, alternatively, a polypeptide of the present invention and a known M. tuberculosis antigen, such as the 38 kD antigen described above or ESAT-6 (SEQ ID NOS: 98 and 99), together with variants of such fusion proteins. The fusion proteins of the present invention may also include a linker peptide between the first and second polypeptides.

A DNA sequence encoding a fusion protein of the present invention is constructed using known recombinant DNA techniques to assemble separate DNA sequences encoding the first and second polypeptides into an appropriate expression vector. The 3' end of a DNA sequence encoding the first polypeptide is ligated, with or without a peptide linker, to the 5' end of a DNA sequence encoding the second polypeptide so that the reading frames of the sequences are in phase to permit mRNA translation of the two DNA sequences into a single fusion protein that retains the biological activity of both the first and the second polypeptides.

A peptide linker sequence may be employed to separate the first and the second polypeptides by a distance sufficient to ensure that each polypeptide folds into its secondary and tertiary structures. Such a peptide linker sequence is incorporated into the fusion protein using standard techniques well known in the art. Suitable peptide linker sequences may be chosen based on the following factors: (1) their ability to adopt a flexible extended conformation; (2) their inability to adopt a secondary structure that could interact with functional epitopes on the first and second polypeptides; and (3) the lack of hydrophobic or charged residues that might react with the polypeptide functional epitopes. Preferred peptide linker sequences contain Gly, Asn and Ser residues. Other near neutral amino acids, such as Thr and Ala may also be used in the linker sequence. Amino acid sequences which may be usefully employed as linkers include those disclosed in Maratea et al, Gene 40:39-46, 1985; Murphy et al., Proc. Natl. Acad. Sci. USA 55:8258-8562, 1986; U.S. Patent No. 4,935,233 and U.S. Patent No. 4,751,180. The linker sequence may be from 1 to about 50 amino acids in length. Peptide linker sequences are not required when the first and second polypeptides have non-essential N-terminal amino acid regions that can be used to separate the functional domains and prevent steric hindrance. In another aspect, the present invention provides methods for using the polypeptides described above to diagnose tuberculosis. In this aspect, methods are provided for detecting M. tuberculosis infection in a biological sample, using one or more of the above polypeptides, alone or in combination. In embodiments in which multiple polypeptides are employed, polypeptides other than those specifically described herein, such as the 38 kD antigen described in Andersen and Hansen, Infect. Immun. 57:2481-2488, 1989, may be included. As used herein, a "biological sample" is any antibody-containing sample obtained from a patient. Preferably, the sample is whole blood, sputum, serum, plasma, saliva, cerebrospinal fluid or urine. More preferably, the sample is a blood, serum or plasma sample obtained from a patient or a blood supply. The polypeptide(s) are used in an assay, as described below, to determine the presence or absence of antibodies to the polypeptide(s) in the sample, relative to a predetermined cut-off value. The presence of such antibodies indicates previous sensitization to mycobacterial antigens which may be indicative of tuberculosis.

In embodiments in which more than one polypeptide is employed, the polypeptides used are preferably complementary (i.e., one component polypeptide will tend to detect infection in samples where the infection would not be detected by another component polypeptide). Complementary polypeptides may generally be identified by using each polypeptide individually to evaluate serum samples obtained from a series of patients known to be infected with M. tuberculosis. After determining which samples test positive (as described below) with each polypeptide, combinations of two or more polypeptides may be formulated that are capable of detecting infection in most, or all, of the samples tested. Such polypeptides are complementary. For example, approximately 25-30%) of sera from tuberculosis-infected individuals are negative for antibodies to any single protein, such as the 38 kD antigen mentioned above. Complementary polypeptides may, therefore, be used in combination with the 38 kD antigen to improve sensitivity of a diagnostic test.

There are a variety of assay formats known to those of ordinary skill in the art for using one or more polypeptides to detect antibodies in a sample. See, e.g., Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, 1988, which is incorporated herein by reference. In a preferred embodiment, the assay involves the use of polypeptide immobilized on a solid support to bind to and remove the antibody from the sample. The bound antibody may then be detected using a detection reagent that contains a reporter group. Suitable detection reagents include antibodies that bind to the antibody /polypeptide complex and free polypeptide labeled with a reporter group (e.g., in a semi-competitive assay). Alternatively, a competitive assay may be utilized, in which an antibody that binds to the polypeptide is labeled with a reporter group and allowed to bind to the immobilized antigen after incubation of the antigen with the sample. The extent to which components of the sample inhibit the binding of the labeled antibody to the polypeptide is indicative of the reactivity of the sample with the immobilized polypeptide.

The solid support may be any solid material known to those of ordinary skill in the art to which the antigen may be attached. For example, the solid support may be a test well in a microtiter plate or a nitrocellulose or other suitable membrane. Alternatively, the support may be a bead or disc, such as glass, fiberglass, latex or a plastic material such as polystyrene or polyvinylchloride. The support may also be a magnetic particle or a fiber optic sensor, such as those disclosed, for example, in U.S. Patent No. 5,359,681. The polypeptides may be bound to the solid support using a variety of techniques known to those of ordinary skill in the art, which are amply described in the patent and scientific literature. In the context of the present invention, the term "bound" refers to both noncovalent association, such as adsorption, and covalent attachment (which may be a direct linkage between the antigen and functional groups on the support or may be a linkage by way of a cross-linking agent). Binding by adsorption to a well in a microtiter plate or to a membrane is preferred. In such cases, adsorption may be achieved by contacting the polypeptide, in a suitable buffer, with the solid support for a suitable amount of time. The contact time varies with temperature, but is typically between about 1 hour and 1 day. In general, contacting a well of a plastic microtiter plate (such as polystyrene or polyvinylchloride) with an amount of polypeptide ranging from about 10 ng to about 1 μg, and preferably about 100 ng, is sufficient to bind an adequate amount of antigen.

Covalent attachment of polypeptide to a solid support may generally be achieved by first reacting the support with a bifunctional reagent that will react with both the support and a functional group, such as a hydroxyl or amino group, on the polypeptide. For example, the polypeptide may be bound to supports having an appropriate polymer coating using benzoquinone or by condensation of an aldehyde group on the support with an amine and an active hydrogen on the polypeptide (see, e.g., Pierce Immunotechnology Catalog and Handbook, 1991, at A12-A13).

In certain embodiments, the assay is an enzyme linked immunosorbent assay (ELISA). This assay may be performed by first contacting a polypeptide antigen that has been immobilized on a solid support, commonly the well of a microtiter plate, with the sample, such that antibodies to the polypeptide within the sample are allowed to bind to the immobilized polypeptide. Unbound sample is then removed from the immobilized polypeptide and a detection reagent capable of binding to the immobilized antibody- polypeptide complex is added. The amount of detection reagent that remains bound to the solid support is then determined using a method appropriate for the specific detection reagent.

More specifically, once the polypeptide is immobilized on the support as described above, the remaining protein binding sites on the support are typically blocked.

Any suitable blocking agent known to those of ordinary skill in the art, such as bovine serum albumin or Tween 20™ (Sigma Chemical Co., St. Louis, MO) may be employed. The immobilized polypeptide is then incubated with the sample, and antibody is allowed to bind to the antigen. The sample may be diluted with a suitable diluent, such as phosphate-buffered saline (PBS) prior to incubation. In general, an appropriate contact time (i.e., incubation time) is that period of time that is sufficient to detect the presence of antibody within a M. tuberculosis-infected sample. Preferably, the contact time is sufficient to achieve a level of binding that is at least 95%) of that achieved at equilibrium between bound and unbound antibody. Those of ordinary skill in the art will recognize that the time necessary to achieve equilibrium may be readily determined by assaying the level of binding that occurs over a period of time. At room temperature, an incubation time of about 30 minutes is generally sufficient.

Unbound sample may then be removed by washing the solid support with an appropriate buffer, such as PBS containing 0.1%) Tween 20™. Detection reagent may then be added to the solid support. An appropriate detection reagent is any compound that binds to the immobilized antibody-polypeptide complex and that can be detected by any of a variety of means known to those in the art. Preferably, the detection reagent contains a binding agent (such as, for example, Protein A, Protein G, immunoglobulin, lectin or free antigen) conjugated to a reporter group. Preferred reporter groups include enzymes (such as horseradish peroxidase), substrates, cofactors, inhibitors, dyes, radionuclides, luminescent groups, fluorescent groups and biotin. The conjugation of binding agent to reporter group may be achieved using standard methods known to those of ordinary skill in the art. Common binding agents may also be purchased conjugated to a variety of reporter groups from many commercial sources (e.g., Zymed Laboratories, San Francisco, CA, and Pierce, Rockford, IL).

The detection reagent is then incubated with the immobilized antibody- polypeptide complex for an amount of time sufficient to detect the bound antibody. An appropriate amount of time may generally be determined from the manufacturer's instructions or by assaying the level of binding that occurs over a period of time. Unbound detection reagent is then removed and bound detection reagent is detected using the reporter group. The method employed for detecting the reporter group depends upon the nature of the reporter group. For radioactive groups, scintillation counting or autoradiographic methods are generally appropriate. Spectroscopic methods may be used to detect dyes, luminescent groups and fluorescent groups. Biotin may be detected using avidin, coupled to a different reporter group (commonly a radioactive or fluorescent group or an enzyme). Enzyme reporter groups may generally be detected by the addition of substrate (generally for a specific period of time), followed by spectroscopic or other analysis of the reaction products. To determine the presence or absence of anti-M tuberculosis antibodies in the sample, the signal detected from the reporter group that remains bound to the solid support is generally compared to a signal that corresponds to a predetermined cut-off value. In one preferred embodiment, the cut-off value is the average mean signal obtained when the immobilized antigen is incubated with samples from an uninfected patient. In general, a sample generating a signal that is three standard deviations above the predetermined cut-off value is considered positive for tuberculosis. In an alternate preferred embodiment, the cutoff value is determined using a Receiver Operator Curve, according to the method of Sackett et al., Clinical Epidemiology: A Basic Science for Clinical Medicine, Little Brown and Co., 1985, pp. 106-107. Briefly, in this embodiment, the cut-off value may be determined from a plot of pairs of true positive rates (i.e., sensitivity) and false positive rates (100%o-specificity) that correspond to each possible cut-off value for the diagnostic test result. The cut-off value on the plot that is the closest to the upper left-hand corner (i. e. , the value that encloses the largest area) is the most accurate cut-off value, and a sample generating a signal that is higher than the cut-off value determined by this method may be considered positive. Alternatively, the cut-off value may be shifted to the left along the plot, to minimize the false positive rate, or to the right, to minimize the false negative rate. In general, a sample generating a signal that is higher than the cut-off value determined by this method is considered positive for tuberculosis. In a related embodiment, the assay is performed in a rapid flow-through or strip test format, wherein the antigen is immobilized on a membrane, such as nitrocellulose. In the flow-through test, antibodies within the sample bind to the immobilized polypeptide as the sample passes through the membrane. A detection reagent (e.g., protein A-colloidal gold) then binds to the antibody-polypeptide complex as the solution containing the detection reagent flows through the membrane. The detection of bound detection reagent may then be performed as described above. In the strip test format, one end of the membrane to which polypeptide is bound is immersed in a solution containing the sample. The sample migrates along the membrane through a region containing detection reagent and to the area of immobilized polypeptide. Concentration of detection reagent at the polypeptide indicates the presence of anti-M tuberculosis antibodies in the sample. Typically, the concentration of detection reagent at that site generates a pattern, such as a line, that can be read visually. The absence of such a pattern indicates a negative result. In general, the amount of polypeptide immobilized on the membrane is selected to generate a visually discernible pattern when the biological sample contains a level of antibodies that would be sufficient to generate a positive signal in an ELISA, as discussed above. Preferably, the amount of polypeptide immobilized on the membrane ranges from about 25 ng to about 1 μg, and more preferably from about 50 ng to about 500 ng. Such tests can typically be performed with a very small amount (e.g., one drop) of patient serum or blood.

Of course, numerous other assay protocols exist that are suitable for use with the polypeptides of the present invention. The above descriptions are intended to be exemplary only.

In yet another aspect, the present invention provides antibodies to the inventive polypeptides. Antibodies may be prepared by any of a variety of techniques known to those of ordinary skill in the art. See, e.g., Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, 1988. In one such technique, an immunogen comprising the antigenic polypeptide is initially injected into any of a wide variety of mammals (e.g., mice, rats, rabbits, sheep and goats). In this step, the polypeptides of this invention may serve as the immunogen without modification. Alternatively, particularly for relatively short polypeptides, a superior immune response may be elicited if the polypeptide is joined to a carrier protein, such as bovine serum albumin or keyhole limpet hemocyanin. The immunogen is injected into the animal host, preferably according to a predetermined schedule incorporating one or more booster immunizations, and the animals are bled periodically. Polyclonal antibodies specific for the polypeptide may then be purified from such antisera by, for example, affinity chromatography using the polypeptide coupled to a suitable solid support.

Monoclonal antibodies specific for the antigenic polypeptide of interest may be prepared, for example, using the technique of Kohler and Milstein, Eur. J. Immunol. 6:511-519, 1976, and improvements thereto. Briefly, these methods involve the preparation of immortal cell lines capable of producing antibodies having the desired specificity (i. e. , reactivity with the polypeptide of interest). Such cell lines may be produced, for example, from spleen cells obtained from an animal immunized as described above. The spleen cells are then immortalized by, for example, fusion with a myeloma cell fusion partner, preferably one that is syngeneic with the immunized animal. A variety of fusion techniques may be employed. For example, the spleen cells and myeloma cells may be combined with a nonionic detergent for a few minutes and then plated at low density on a selective medium that supports the growth of hybrid cells, but not myeloma cells. A preferred selection technique uses HAT (hypoxanthine, aminopterin, thymidine) selection. After a sufficient time, usually about 1 to 2 weeks, colonies of hybrids are observed. Single colonies are selected and tested for binding activity against the polypeptide. Hybridomas having high reactivity and specificity are preferred.

Monoclonal antibodies may be isolated from the supernatants of growing hybridoma colonies. In addition, various techniques may be employed to enhance the yield, such as injection of the hybridoma cell line into the peritoneal cavity of a suitable vertebrate host, such as a mouse. Monoclonal antibodies may then be harvested from the ascites fluid or the blood. Contaminants may be removed from the antibodies by conventional techniques, such as chromatography, gel filtration, precipitation, and extraction. The polypeptides of this invention may be used in the purification process in, for example, an affinity chromatography step.

Antibodies may be used in diagnostic tests to detect the presence of M. tuberculosis antigens using assays similar to those detailed above and other techniques well known to those of skill in the art, thereby providing a method for detecting M tuberculosis infection in a patient.

Diagnostic reagents of the present invention may also comprise DNA sequences encoding one or more of the above polypeptides, or one or more portions thereof. For example, at least two oligonucleotide primers may be employed in a polymerase chain reaction (PCR) based assay to amplify M. tuberculosis-specific cDNA derived from a biological sample, wherein at least one of the oligonucleotide primers is specific for a DNA molecule encoding a polypeptide of the present invention. The presence of the amplified cDNA is then detected using techniques well known in the art, such as gel electrophoresis. Similarly, oligonucleotide probes specific for a DNA molecule encoding a polypeptide of the present invention may be used in a hybridization assay to detect the presence of an inventive polypeptide in a biological sample.

As used herein, the term "oligonucleotide primer/probe specific for a DNA molecule" means an oligonucleotide sequence that has at least about 80%>, preferably at least about 90%) and more preferably at least about 95%>, identity to the DNA molecule in question. Oligonucleotide primers and/or probes which may be usefully employed in the inventive diagnostic methods preferably have at least about 10-40 nucleotides. In a preferred embodiment, the oligonucleotide primers comprise at least about 10 contiguous nucleotides of a DNA molecule encoding one of the polypeptides disclosed herein. Preferably, oligonucleotide probes for use in the inventive diagnostic methods comprise at least about 15 contiguous oligonucleotides of a DNA molecule encoding one of the polypeptides disclosed herein. Techniques for both PCR based assays and hybridization assays are well known in the art (see, for example, Mullis et al. Ibid; Ehrlich, Ibid). Primers or probes may thus be used to detect M tuberculosis-specific sequences in biological samples. DNA probes or primers comprising oligonucleotide sequences described above may be used alone, in combination with each other, or with previously identified sequences, such as the 38 kD antigen discussed above.

The following Examples are offered by way of illustration and not by way of limitation.

EXAMPLES

EXAMPLE 1 PURIFICATION AND CHARACTERIZATION OF POLYPEPTIDES

FROM M TUBERCULOSIS CULTURE FILTRATE

This example illustrates the preparation of M. tuberculosis soluble polypeptides from culture filtrate. Unless otherwise noted, all percentages in the following example are weight per volume. M. tuberculosis (either H37Ra, ATCC No. 25177, or H37Rv, ATCC No. 25618) was cultured in sterile GAS media at 37°C for fourteen days. The media was then vacuum filtered (leaving the bulk of the cells) through a 0.45 μ filter into a sterile 2.5 L bottle. The media was then filtered through a 0.2 μ filter into a sterile 4 L bottle. NaN₃ was then added to the culture filtrate to a concentration of 0.04%). The bottles were then placed in a 4°C cold room.

The culture filtrate was concentrated by placing the filtrate in a 12 L reservoir that had been autoclaved and feeding the filtrate into a 400 ml Amicon stir cell which had been rinsed with ethanol and contained a 10,000 kDa MWCO membrane. The pressure was maintained at 60 psi using nitrogen gas. This procedure reduced the 12 L volume to approximately 50 ml.

The culture filtrate was then dialyzed into 0.1% ammonium bicarbonate using a 8,000 kDa MWCO cellulose ester membrane, with two changes of ammonium bicarbonate solution. Protein concentration was then determined by a commercially available BCA assay (Pierce, Rockford, IL).

The dialyzed culture filtrate was then lyophilized, and the polypeptides resuspended in distilled water. The polypeptides were then dialyzed against 0.01 mM 1,3 bis[tris(hydroxymethyl)-methylamino]propane, pH 7.5 (Bis-Tris propane buffer), the initial conditions for anion exchange chromatography. Fractionation was performed using gel profusion chromatography on a POROS 146 II Q/M anion exchange column 4.6 mm x 100 mm (Perseptive BioSystems, Framingham, MA) equilibrated in 0.01 mM Bis-Tris propane buffer pH 7.5. Polypeptides were eluted with a linear 0-0.5 M NaCl gradient in the above buffer system. The column eluent was monitored at a wavelength of 220 nm.

The pools of polypeptides eluting from the ion exchange column were dialyzed against distilled water and lyophilized. The resulting material was dissolved in 0.1%) trifluoroacetic acid (TFA) pH 1.9 in water, and the polypeptides were purified on a Delta-Pak C18 column (Waters, Milford, MA) 300 Angstrom pore size, 5 micron particle size (3.9 x 150 mm). The polypeptides were eluted from the column with a linear gradient from 0-60%> dilution buffer (0.1%o TFA in acetonitrile). The flow rate was 0.75 ml/minute and the HPLC eluent was monitored at 214 nm. Fractions containing the eluted polypeptides were collected to maximize the purity of the individual samples. Approximately 200 purified polypeptides were obtained.

The purified polypeptides were then screened for the ability to induce T-cell proliferation in PBMC preparations. The PBMCs from donors known to be PPD skin test positive and whose T cells were shown to proliferate in response to PPD and crude soluble proteins from MTB were cultured in medium comprising RPMI 1640 supplemented with 10%) pooled human serum and 50 μg/ml gentamicin. Purified polypeptides were added in duplicate at concentrations of 0.5 to 10 μg/mL. After six days of culture in 96-well round- bottom plates in a volume of 200 μl, 50 μl of medium was removed from each well for determination of IFN-γ levels, as described below. The plates were then pulsed with 1 μCi/well of tritiated thymidine for a further 18 hours, harvested and tritium uptake determined using a gas scintillation counter. Fractions that resulted in proliferation in both replicates three fold greater than the proliferation observed in cells cultured in medium alone were considered positive. IFN-γ was measured using an enzyme-linked immunosorbent assay (ELISA).

ELISA plates were coated with a mouse monoclonal antibody directed to human IFN-γ (Chemicon) in PBS for four hours at room temperature. Wells were then blocked with PBS containing 5% (W/V) non-fat dried milk for 1 hour at room temperature. The plates were then washed six times in PBS/0.2%> TWEEN-20 and samples diluted 1 :2 in culture medium in the ELISA plates were incubated overnight at room temperature. The plates were again washed and a polyclonal rabbit anti-human IFN-γ serum diluted 1 :3000 in PBS/10%> normal goat serum was added to each well. The plates were then incubated for two hours at room temperature, washed and horseradish peroxidase-coupled anti-rabbit IgG (Jackson Labs.) was added at a 1 :2000 dilution in PBS/5%> non-fat dried milk. After a further two hour incubation at room temperature, the plates were washed and TMB substrate added. The reaction was stopped after 20 min with 1 N sulfuric acid. Optical density was determined at 450 nm using 570 nm as a reference wavelength. Fractions that resulted in both replicates giving an OD two fold greater than the mean OD from cells cultured in medium alone, plus 3 standard deviations, were considered positive. For sequencing, the polypeptides were individually dried onto Biobrene™ (Perkin Elmer/ Applied BioSystems Division, Foster City, CA) treated glass fiber filters. The filters with polypeptide were loaded onto a Perkin Elmer/ Applied BioSystems Division Procise 492 protein sequencer. The polypeptides were sequenced from the amino terminal and using traditional Edman chemistry. The amino acid sequence was determined for each polypeptide by comparing the retention time of the PTH amino acid derivative to the appropriate PTH derivative standards.

Using the procedure described above, antigens having the following N-terminal sequences were isolated: (a) Asp-Pro- Val-Asp- Ala- Val-Ile-Asn-Thr-Thr-Xaa- Asn-Tyr-Gly-Gln-

Val-Val-Ala-Ala-Leu (SEQ ID NO: 54);

(b) Ala-Val-Glu-Ser-Gly-Met-Leu-Ala-Leu-Gly-Thr-Pro-Ala-Pro-Ser (SEQ ID NO: 55);

(c) Ala-Ala-Met-Lys-Pro-Arg-Thr-Gly-Asp-Gly-Pro-Leu-Glu-Ala-Ala- Lys-Glu-Gly-Arg (SEQ ID NO: 56);

(d) Tyr-Tyr-Trp-Cys-Pro-Gly-Gln-Pro-Phe-Asp-Pro-Ala-Trp-Gly-Pro (SEQ ID NO: 57);

(e) Asp-Ile-Gly-Ser-Glu-Ser-Thr-Glu-Asp-Gln-Gln-Xaa-Ala-Val (SEQ ID NO: 58); (f) Ala-Glu-Glu-Ser-Ile-Ser-Thr-Xaa-Glu-Xaa-Ile-Val-Pro (SEQ ID

NO: 59); (g) Asp-Pro-Glu-Pro-Ala-Pro-Pro-Val-Pro-Thr- Ala- Ala- Ala-Ala-Pro-Pro- Ala (SEQ ID NO: 60); and (h) Ala-Pro-Lys-Thr-Tyr-Xaa-Glu-Glu-Leu-Lys-Gly-Thr-Asp-Thr-Gly (SEQ ID NO: 61); wherein Xaa may be any amino acid.

An additional antigen was isolated employing a microbore HPLC purification step in addition to the procedure described above. Specifically, 20 μl of a fraction comprising a mixture of antigens from the chromatographic purification step previously described, was purified on an Aquapore C18 column (Perkin Elmer/ Applied Biosystems Division, Foster City, CA) with a 7 micron pore size, column size 1 mm x 100 mm, in a Perkin Elmer/ Applied Biosy stems Division Model 172 HPLC. Fractions were eluted from the column with a linear gradient of l%>/minute of acetonitrile (containing 0.05%> TFA) in water (0.05% TFA) at a flow rate of 80 μl/minute. The eluent was monitored at 250 nm. The original fraction was separated into 4 major peaks plus other smaller components and a polypeptide was obtained which was shown to have a molecular weight of 12.054 Kd (by mass spectrometry) and the following N-terminal sequence:

(i) Asp-Pro-Ala-Ser-Ala-Pro-Asp-Val-Pro-Thr-Ala-Ala-Gln-Gln-Thr-Ser- Leu-Leu-Asn-Asn-Leu-Ala-Asp-Pro-Asp-Val-Ser-Phe-Ala-Asp (SEQ ID NO: 62).

This polypeptide was shown to induce proliferation and IFN-γ production in PBMC preparations using the assays described above.

Additional soluble antigens were isolated from M. tuberculosis culture filtrate as follows. M tuberculosis culture filtrate was prepared as described above. Following dialysis against Bis-Tris propane buffer, at pH 5.5, fractionation was performed using anion exchange chromatography on a Poros QE column 4.6 x 100 mm (Perseptive Biosystems) equilibrated in Bis-Tris propane buffer pH 5.5. Polypeptides were eluted with a linear 0-1.5 M NaCl gradient in the above buffer system at a flow rate of 10 ml/min. The column eluent was monitored at a wavelength of 214 nm. The fractions eluting from the ion exchange column were pooled and subjected to reverse phase chromatography using a Poros R2 column 4.6 x 100 mm (Perseptive Biosystems). Polypeptides were eluted from the column with a linear gradient from 0-100% acetonitrile (0.1% TFA) at a flow rate of 5 ml/min. The eluent was monitored at 214 nm. Fractions containing the eluted polypeptides were lyophilized and resuspended in 80 μl of aqueous 0.1 % TFA and further subjected to reverse phase chromatography on a Vydac C4 column 4.6 x 150 mm (Western Analytical, Temecula, CA) with a linear gradient of 0-100%) acetonitrile (0.1 % TFA) at a flow rate of 2 ml/min. Eluent was monitored at 214 nm. The fraction with biological activity was separated into one major peak plus other smaller components. Western blot of this peak onto PVDF membrane revealed three major bands of molecular weights 14 Kd, 20 Kd and 26 Kd. These polypeptides were determined to have the following N-terminal sequences, respectively: (j) Xaa-Asp-Ser-Glu-Lys-Ser-Ala-Thr-Ile-Lys-Val-Thr-Asp-Ala-Ser;

(SEQ ID NO: 130) and (1) Ala-Pro-Glu-Ser-Gly-Ala-Gly-Leu-Gly-Gly-Thr-Val-Gln-Ala-Gly; (SEQ ID NO: 131), wherein Xaa may be any amino acid.

Using the assays described above, these polypeptides were shown to induce proliferation and IFN-γ production in PBMC preparations. Figs. 1A and B show the results of such assays using PBMC preparations from a first and a second donor, respectively.

DNA sequences that encode the antigens designated as (a), (c), (d) and (g) above were obtained by screening a M. tuberculosis genomic library using ³²P end labeled degenerate oligonucleotides corresponding to the N-terminal sequence and containing

M tuberculosis codon bias. The screen performed using a probe corresponding to antigen (a) above identified a clone having the sequence provided in SEQ ID NO: 96. The polypeptide encoded by SEQ ID NO: 96 is provided in SEQ ID NO: 97. The screen performed using a probe corresponding to antigen (g) above identified a clone having the sequence provided in

SEQ ID NO: 52. The polypeptide encoded by SEQ ID NO: 52 is provided in SEQ ID

NO: 53. The screen performed using a probe corresponding to antigen (d) above identified a clone having the sequence provided in SEQ ID NO: 24, and the screen performed with a probe corresponding to antigen (c) identified a clone having the sequence provided in SEQ ID NO: 25.

The above amino acid sequences were compared to known amino acid sequences in the gene bank using the DNA STAR system. The database searched contains some 173,000 proteins and is a combination of the Swiss, PIR databases along with translated protein sequences (Version 87). No significant homologies to the amino acid sequences for antigens (a)-(h) and (1) were detected. The amino acid sequence for antigen (i) was found to be homologous to a sequence from M. leprae. The full length M leprae sequence was amplified from genomic

DNA using the sequence obtained from GENBANK. This sequence was then used to screen an M tuberculosis library and a full length copy of the M. tuberculosis homologue was obtained (SEQ ID NO: 94).

The amino acid sequence for antigen (j) was found to be homologous to a known M tuberculosis protein translated from a DNA sequence. To the best of the inventors' knowledge, this protein has not been previously shown to possess T-cell stimulatory activity. The amino acid sequence for antigen (k) was found to be related to a sequence from M leprae.

In the proliferation and IFN-γ assays described above, using three PPD positive donors, the results for representative antigens provided above are presented in Table 1 :

TABLE 1 RESULTS OF PBMC PROLIFERATION AND IFN-γ ASSAYS

In Table 1 , responses that gave a stimulation index (SI) of between 2 and 4 (compared to cells cultured in medium alone) were scored as +, as SI of 4-8 or 2-4 at a concentration of 1 μg or less was scored as ++ and an SI of greater than 8 was scored as +++.

The antigen of sequence (i) was found to have a high SI (+++) for one donor and lower SI

(++ and +) for the two other donors in both proliferation and IFN-γ assays. These results indicate that these antigens are capable of inducing proliferation and/or interferon-γ production.

EXAMPLE 2 USE OF PATIENT SERA TO ISOLATE M TUBERCULOSIS ANTIGENS

This example illustrates the isolation of antigens from M tuberculosis lysate by screening with serum from M tuberculosis-infected individuals.

Dessicated M tuberculosis H37Ra (Difco Laboratories) was added to a 2% NP40 solution, and alternately homogenized and sonicated three times. The resulting suspension was centrifuged at 13,000 rpm in micro fuge tubes and the supernatant put through a 0.2 micron syringe filter. The filtrate was bound to Macro Prep DEAE beads (BioRad,

Hercules, CA). The beads were extensively washed with 20 mM Tris pH 7.5 and bound proteins eluted with 1M NaCl. The NaCl elute was dialyzed overnight against 10 mM Tris, pH 7.5. Dialyzed solution was treated with DNase and RNase at 0.05 mg/ml for 30 min. at room temperature and then with α-D-mannosidase, 0.5 U/mg at pH 4.5 for 3-4 hours at room temperature. After returning to pH 7.5, the material was fractionated via FPLC over a Bio

Scale-Q-20 column (BioRad). Fractions were combined into nine pools, concentrated in a

Centriprep 10 (Amicon, Beverley, MA) and screened by Western blot for serological activity using a serum pool from M. tuberculosis-infected patients which was not immunoreactive with other antigens of the present invention.

The most reactive fraction was run in SDS-PAGE and transferred to PVDF. A band at approximately 85 Kd was cut out yielding the sequence:

(m) Xaa-Tyr-Ile-Ala-Tyr-Xaa-Thr-Thr-Ala-Gly-Ile-Val-Pro-Gly-Lys-Ile- Asn-Val-His-Leu-Val; (SEQ ID NO: 132), wherein Xaa may be any amino acid. Comparison of this sequence with those in the gene bank as described above, revealed no significant homologies to known sequences.

A DNA sequence that encodes the antigen designated as (m) above was obtained by screening a genomic M tuberculosis Erdman strain library using labeled degenerate oligonucleotides corresponding to the N-terminal sequence of SEQ ID NO: 137. A clone was identified having the DNA sequence provided in SEQ ID NO: 198. This sequence was found to encode the amino acid sequence provided in SEQ ID NO: 199. Comparison of these sequences with those in the genebank revealed some similarity to sequences previously identified in M tuberculosis and M bovis.

EXAMPLE 3 PREPARATION OF DNA SEQUENCES ENCODING M TUBERCULOSIS ANTIGENS

This example illustrates the preparation of DNA sequences encoding

M. tuberculosis antigens by screening a M tuberculosis expression library with sera obtained from patients infected with M tuberculosis, or with anti-sera raised against M. tuberculosis antigens.

A. PREPARATION OF M. TUBERCULOSIS SOLUBLE ANTIGENS USING RABBIT ANTI-SERA RAISED AGAINST M. TUBERCULOSIS SUPERNATANT

Genomic DNA was isolated from the M. tuberculosis strain H37Ra. The DNA was randomly sheared and used to construct an expression library using the Lambda ZAP expression system (Stratagene, La Jolla, CA). Rabbit anti-sera was generated against secretory proteins of the M tuberculosis strains H37Ra, H37Rv and Erdman by immunizing a rabbit with concentrated supernatant of the M. tuberculosis cultures. Specifically, the rabbit was first immunized subcutaneously with 200 μg of protein antigen in a total volume of 2 ml containing 100 μg muramyl dipeptide (Calbiochem, La Jolla, CA) and 1 ml of incomplete Freund's adjuvant. Four weeks later the rabbit was boosted subcutaneously with 100 μg antigen in incomplete Freund's adjuvant. Finally, the rabbit was immunized intravenously four weeks later with 50 μg protein antigen. The anti-sera were used to screen the expression library as described in Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratories, Cold Spring Harbor, NY, 1989. Bacteriophage plaques expressing immunoreactive antigens were purified. Phagemid from the plaques was rescued and the nucleotide sequences of the M tuberculosis clones deduced. Thirty two clones were purified. Of these, 25 represent sequences that have not been previously identified in M tuberculosis. Proteins were induced by IPTG and purified by gel elution, as described in Skeiky et al., J Exp. Med. 757:1527-1537, 1995. Representative partial sequences of DNA molecules identified in this screen are provided in SEQ ID NOS: 1-25. The corresponding predicted amino acid sequences are shown in SEQ ID NOS: 64-88.

On comparison of these sequences with known sequences in the gene bank using the databases described above, it was found that the clones referred to hereinafter as TbRA2A, TbRA16, TbRA18, and TbRA29 (SEQ ID NOS: 77, 69, 71, 76) show some homology to sequences previously identified in Mycobacterium leprae but not in M tuberculosis. TbRAl l, TbRA26, TbRA28 and TbDPEP (SEQ ID NOS: 66, 74, 75, 53) have been previously identified in M tuberculosis. No significant homologies were found to TbRAl, TbRA3, TbRA4, TbRA9, TbRAlO, TbRA13, TbRA17, TbRA19, TbRA29, TbRA32, TbRA36 and the overlapping clones TbRA35 and TbRA12 (SEQ ID NOS: 64, 78, 82, 83, 65, 68, 76, 72, 76, 79, 81, 80, 67, respectively). The clone TbRa24 is overlapping with clone TbRa29.

B. USE OF SERA FROM PATIENTS HAVING PULMONARY OR PLEURAL TUBERCULOSIS TO IDENTIFY DNA SEQUENCES ENCODING M. TUBERCULOSIS ANTIGENS The genomic DNA library described above, and an additional H37Rv library, were screened using pools of sera obtained from patients with active tuberculosis. To prepare the H37Rv library, M tuberculosis strain H37Rv genomic DNA was isolated, subjected to partial Sau3A digestion and used to construct an expression library using the Lambda Zap expression system (Stratagene, La Jolla, Ca). Three different pools of sera, each containing sera obtained from three individuals with active pulmonary or pleural disease, were used in the expression screening. The pools were designated TbL, TbM and TbH, referring to relative reactivity with H37Ra lysate (i.e., TbL - low reactivity, TbM = medium reactivity and TbH = high reactivity) in both ELISA and immunoblot format. A fourth pool of sera from seven patients with active pulmonary tuberculosis was also employed. All of the sera lacked increased reactivity with the recombinant 38 kD M tuberculosis H37Ra phosphate- binding protein.

All pools were pre-adsorbed with E. coli lysale and used to screen the H37Ra and H37Rv expression libraries, as described in Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratories, Cold Spring Harbor, NY, 1989.

Bacteriophage plaques expressing immunoreactive antigens were purified. Phagemid from the plaques was rescued and the nucleotide sequences of the M tuberculosis clones deduced.

Thirty two clones were purified. Of these, 31 represented sequences that had not been previously identified in human M tuberculosis. Representative sequences of the DNA molecules identified are provided in SEQ ID NOS:: 26-51 and 100. Of these, TbH-8-2 (SEQ. ID NO. 100) is a partial clone of TbH-8, and TbH-4 (SEQ. ID NO. 43) and TbH-4- FWD (SEQ. ID NO. 44) are non-contiguous sequences from the same clone. Amino acid sequences for the antigens hereinafter identified as Tb38-1, TbH-4, TbH-8, TbH-9, and TbH-12 are shown in SEQ ID NOS.: 89-93. Comparison of these sequences with known sequences in the gene bank using the databases identified above revealed no significant homologies to TbH-4, TbH-8, TbH-9 and TbM-3, although weak homologies were found to TbH-9. TbH-12 was found to be homologous to a 34 kD antigenic protein previously identified in M. paratuberculosis (Ace. No. S28515). Tb38-1 was found to be located 34 base pairs upstream of the open reading frame for the antigen ESAT-6 previously identified in M bovis (Ace. No. U34848) and in M tuberculosis (Sorensen et al., Infec. Immun. 63:1710-1717, 1995).

Probes derived from Tb38-1 and TbH-9, both isolated from an H37Ra library, were used to identify clones in an H37Rv library. Tb38-1 hybridized to Tb38-1F2, Tb38- 1F3, Tb38-1F5 and Tb38-1F6 (SEQ. ID NOS: 107, 108, 111, 113, and 114). (SEQ ID NOS: 107 and 108 are non-contiguous sequences from clone Tb38-1F2.) Two open reading frames were deduced in Tb38-IF2; one corresponds to Tb37FL (SEQ. ID. NO. 109), the second, a partial sequence, may be the homologue of Tb38-1 and is called Tb38-IN (SEQ. ID NO. 110). The deduced amino acid sequence of Tb38-1F3 is presented in SEQ. ID. NO. 112. A TbH-9 probe identified three clones in the H37Rv library: TbH-9-FL (SEQ. ID NO. 101), which may be the homologue of TbH-9 (R37Ra), TbH-9-1 (SEQ. ID NO. 103), and TbH-8-2 (SEQ. ID NO. 105) is a partial clone of TbH-8. The deduced amino acid sequences for these three clones are presented in SEQ ID NOS: 102, 104 and 106.

Further screening of the M. tuberculosis genomic DNA library, as described above, resulted in the recovery of ten additional reactive clones, representing seven different genes. One of these genes was identified as the 38 Kd antigen discussed above, one was determined to be identical to the 14Kd alpha crystallin heat shock protein previously shown to be present in M tuberculosis, and a third was determined to be identical to the antigen TbH-8 described above. The determined DNA sequences for the remaining five clones (hereinafter referred to as TbH-29, TbH-30, TbH-32 and TbH-33) are provided in SEQ ID NO: 133-136, respectively, with the corresponding predicted amino acid sequences being provided in SEQ ID NO: 137-140, respectively. The DNA and amino acid sequences for these antigens were compared with those in the gene bank as described above. No homologies were found to the 5' end of TbH-29 (which contains the reactive open reading frame), although the 3' end of TbH-29 was found to be identical to the M tuberculosis cosmid Y227. TbH-32 and TbH-33 were found to be identical to the previously identified M tuberculosis insertion element IS6110 and to the M tuberculosis cosmid Y50, respectively. No significant homologies to TbH-30 were found.

Positive phagemid from this additional screening were used to infect E. coli XL-1 Blue MRF', as described in Sambrook et al., supra. Induction of recombinant protein was accomplished by the addition of IPTG. Induced and uninduced lysates were run in duplicate on SDS-PAGE and transferred to nitrocellulose filters. Filters were reacted with human M. tuberculosis sera (1 :200 dilution) reactive with TbH and a rabbit sera (1 :200 or 1 :250 dilution) reactive with the N-terminal 4 Kd portion of lacZ. Sera incubations were performed for 2 hours at room temperature. Bound antibody was detected by addition of ¹²⁵I- labeled Protein A and subsequent exposure to film for variable times ranging from 16 hours to 11 days. The results of the immunoblots are summarized in Table 2. TABLE 2

Human M. tb Anti-lacZ

Antigen Sera Sera

TbH-29 45 Kd 45 Kd

TbH-30 No reactivity 29 Kd

TbH-32 12 Kd 12 Kd

TbH-33 16 Kd 16 Kd

Positive reaction of the recombinant human M tuberculosis antigens with both the human M tuberculosis sera and anti-lacZ sera indicate that reactivity of the human M tuberculosis sera is directed towards the fusion protein. Antigens reactive with the anti-lacZ sera but not with the human M. tuberculosis sera may be the result of the human M tuberculosis sera recognizing conformational epitopes, or the antigen-antibody binding kinetics may be such that the 2 hour sera exposure in the immunoblot is not sufficient.

Studies were undertaken to determine whether the antigens TbH-9 and Tb38-1 represent cellular proteins or are secreted into M. tuberculosis culture media. In the first study, rabbit sera were raised against A) secretory proteins of M. tuberculosis, B) the known secretory recombinant M tuberculosis antigen 85b, C) recombinant Tb38-1 and D) recombinant TbH-9, using protocols substantially as described in Example 3A. Total M tuberculosis lysate, concentrated supernatant of M tuberculosis cultures and the recombinant antigens 85b, TbH-9 and Tb38-1 were resolved on denaturing gels, immobilized on nitrocellulose membranes and duplicate blots were probed using the rabbit sera described above.

The results of this analysis using control sera (panel I) and antisera (panel II) against secretory proteins, recombinant 85b, recombinant Tb38-1 and recombinant TbH-9 are shown in Figures 2A-D, respectively, wherein the lane designations are as follows: 1) molecular weight protein standards; 2) 5 μg of M tuberculosis lysate; 3) 5 μg secretory proteins; 4) 50 ng recombinant Tb38-1; 5) 50 ng recombinant TbH-9; and 6) 50 ng recombinant 85b. The recombinant antigens were engineered with six terminal histidine residues and would therefore be expected to migrate with a mobility approximately 1 kD larger that the native protein. In Figure 2D, recombinant TbH-9 is lacking approximately 10 kD of the full-length 42 kD antigen, hence the significant difference in the size of the immunoreactive native TbH-9 antigen in the lysate lane (indicated by an arrow). These results demonstrate that Tb38-1 and TbH-9 are intracellular antigens and are not actively secreted by M tuberculosis.

The finding that TbH-9 is an intracellular antigen was confirmed by determining the reactivity of TbH-9-specific human T cell clones to recombinant TbH-9, secretory M tuberculosis proteins and PPD. A TbH-9-specific T cell clone (designated 131TbH-9) was generated from PBMC of a healthy PPD-positive donor. The proliferative response of 131TbH-9 to secretory proteins, recombinant TbH-9 and a control M. tuberculosis antigen, TbRal 1, was determined by measuring uptake of tritiated thymidine, as described in Example 1. As shown in Figure 3 A, the clone 131TbH-9 responds specifically to TbH-9, showing that TbH-9 is not a significant component of M. tuberculosis secretory proteins. Figure 3B shows the production of IFN-γ by a second TbH-9-specific T cell clone (designated PPD 800-10) prepared from PBMC from a healthy PPD-positive donor, following stimulation of the T cell clone with secretory proteins, PPD or recombinant TbH-9. These results further confirm that TbH-9 is not secreted by M tuberculosis.

C. USE OF SERA FROM PATIENTS HAVING EXTRAPULMONARY TUBERCULOSIS TO IDENTIFY DNA SEQUENCES ENCODING M TUBERCULOSIS ANTIGENS

Genomic DNA was isolated from M tuberculosis Erdman strain, randomly sheared and used to construct an expression library employing the Lambda ZAP expression system (Stratagene, La Jolla, CA). The resulting library was screened using pools of sera obtained from individuals with extrapulmonary tuberculosis, as described above in Example 3B, with the secondary antibody being goat anti-human IgG + A + M (H+L) conjugated with alkaline phosphatase.

Eighteen clones were purified. Of these, 4 clones (hereinafter referred to as XP14, XP24, XP31 and XP32) were found to bear some similarity to known sequences. The determined DNA sequences for XP14, XP24 and XP31 are provided in SEQ ID NOS: 151- 153, respectively, with the 5' and 3' DNA sequences for XP32 being provided in SEQ ID NOS: 154 and 155, respectively. The predicted amino acid sequence for XP14 is provided in SEQ ID NO: 156. The reverse complement of XP14 was found to encode the amino acid sequence provided in SEQ ID NO: 157. Comparison of the sequences for the remaining 14 clones (hereinafter referred to as XP1-XP6, XP17-XP19, XP22, XP25, XP27, XP30 and XP36) with those in the genebank as described above, revealed no homologies with the exception of the 3 ' ends of XP2 and XP6 which were found to bear some homology to known M tuberculosis cosmids. The DNA sequences for XP27 and XP36 are shown in SEQ ID NOS: 158 and 159, respectively, with the 5' sequences for XP4, XP5, XP17 and XP30 being shown in SEQ ID NOS: 160-163, respectively, and the 5' and 3' sequences for XP2, XP3, XP6, XP18, XP19, XP22 and XP25 being shown in SEQ ID NOS: 164 and 165; 166 and 167; 168 and 169; 170 and 171; 172 and 173; 174 and 175; and 176 and 177, respectively. XP1 was found to overlap with the DNA sequences for TbH4, disclosed above. The full-length DNA sequence for TbH4-XPl is provided in SEQ ID NO: 178. This DNA sequence was found to contain an open reading frame encoding the amino acid sequence shown in SEQ ID NO: 179. The reverse complement of TbH4-XPl was found to contain an open reading frame encoding the amino acid sequence shown in SEQ ID NO: 180. The DNA sequence for XP36 was found to contain two open reading frames encoding the amino acid sequence shown in SEQ ID NOS: 181 and 182, with the reverse complement containing an open reading frame encoding the amino acid sequence shown in SEQ ID NO: 183.

Recombinant XP1 protein was prepared as described above in Example 3B, with a metal ion affinity chromatography column being employed for purification. Recombinant XP1 was found to stimulate cell proliferation and IFN-γ production in T cells isolated from an M. tuberculosis-immune donors.

D. PREPARATION OF M. TUBERCULOSIS SOLUBLE ANTIGENS USING RABBIT ANTI-SERA RAISED AGAINST M. TUBERCULOSIS FRACTIONATED PROTEINS

M. tuberculosis lysate was prepared as described above in Example 2. The resulting material was fractionated by HPLC and the fractions screened by Western blot for serological activity with a serum pool from M. tuberculosis-infected patients which showed little or no immunoreactivity with other antigens of the present invention. Rabbit anti-sera was generated against the most reactive fraction using the method described in Example 3 A . The anti-sera was used to screen an M tuberculosis Erdman strain genomic DNA expression library prepared as described above. Bacteriophage plaques expressing immunoreactive antigens were purified. Phagemid from the plaques was rescued and the nucleotide sequences of the M. tuberculosis clones determined.

Ten different clones were purified. Of these, one was found to be TbRa35, described above, and one was found to be the previously identified M tuberculosis antigen, HSP60. Of the remaining eight clones, six (hereinafter referred to as RDIF2, RDIF5, RDIF8, RDIF 10, RDIF 11 and RDIF 12) were found to bear some similarity to previously identified M. tuberculosis sequences. The determined DNA sequences for RDIF2, RDIF5, RDIF8, RDIF10 and RDIF 11 are provided in SEQ ID NOS: 184-188, respectively, with the corresponding predicted amino acid sequences being provided in SEQ ID NOS: 189-193, respectively. The 5^" and 3' DNA sequences for RDIF 12 are provided in SEQ ID NOS: 194 and 195, respectively. No significant homologies were found to the antigen RDIF-7. The determined DNA and predicted amino acid sequences for RDIF7 are provided in SEQ ID NOS: 196 and 197, respectively. One additional clone, referred to as RDIF6 was isolated, however, this was found to be identical to RDIF5. Recombinant RDIF6, RDIF8, RDIF 10 and RDIF 11 were prepared as described above. These antigens were found to stimulate cell proliferation and IFN-γ production in T cells isolated from M. tuberculosis-immune donors.

EXAMPLE 4

PURIFICATION AND CHARACTERIZATION OF A POLYPEPTIDE FROM TUBERCULIN PURIFIED

PROTEIN DERIVATIVE

An M. tuberculosis polypeptide was isolated from tuberculin purified protein derivative (PPD) as follows. PPD was prepared as published with some modification (Seibert, F. et al., Tuberculin purified protein derivative. Preparation and analyses of a large quantity for standard. The American Review of Tuberculosis 44:9-25, 1941). M. tuberculosis Rv strain was grown for 6 weeks in synthetic medium in roller bottles at 37°C. Bottles containing the bacterial growth were then heated to 100°C in water vapor for 3 hours. Cultures were sterile filtered using a 0.22 μ filter and the liquid phase was concentrated 20 times using a 3 kD cutoff membrane. Proteins were precipitated once with 50% ammonium sulfate solution and eight times with 25% ammonium sulfate solution. The resulting proteins (PPD) were fractionated by reverse phase liquid chromatography (RP-HPLC) using a C18 column (7.8 x 300 mM; Waters, Milford, MA) in a Biocad HPLC system (Perseptive Biosystems, Framingham, MA). Fractions were eluted from the column with a linear gradient from 0- 100%) buffer (0.1%o TFA in acetonitrile). The flow rate was 10 ml/minute and eluent was monitored at 214 nm and 280 nm.

Six fractions were collected, dried, suspended in PBS and tested individually in M tuberculosis-infected guinea pigs for induction of delayed type hypersensitivity (DTH) reaction. One fraction was found to induce a strong DTH reaction and was subsequently fractionated further by RP-HPLC on a microbore Vydac C18 column (Cat. No. 218TP5115) in a Perkin Elmer/ Applied Biosystems Division Model 172 HPLC. Fractions were eluted with a linear gradient from 5-100% buffer (0.05%) TFA in acetonitrile) with a flow rate of 80 μl/minute. Eluent was monitored at 215 nm. Eight fractions were collected and tested for induction of DTH in M. tuberculosis-infected guinea pigs. One fraction was found to induce strong DTH of about 16 mm induration. The other fractions did not induce detectable DTH. The positive fraction was submitted to SDS-PAGE gel electrophoresis and found to contain a single protein band of approximately 12 kD molecular weight. This polypeptide, herein after referred to as DPPD, was sequenced from the amino terminal using a Perkin Elmer/Applied Biosystems Division Procise 492 protein sequencer as described above and found to have the N-terminal sequence shown in SEQ ID NO:: 124. Comparison of this sequence with known sequences in the gene bank as described above revealed no known homologies. Four cyanogen bromide fragments of DPPD were isolated and found to have the sequences shown in SEQ ID NOS: 125-128. EXAMPLE 5 SYNTHESIS OF SYNTHETIC POLYPEPTIDES

Polypeptides may be synthesized on a Millipore 9050 peptide synthesizer using FMOC chemistry with HPTU (0-Benzotriazole-N,N,N',N'-tetramethyluronium hexafluorophosphate) activation. A Gly-Cys-Gly sequence may be attached to the amino terminus of the peptide to provide a method of conjugation or labeling of the peptide. Cleavage of the peptides from the solid support may be carried out using the following cleavage mixture: trifluoroacetic acid:ethanedithiol:thioanisole:water:phenol (40:1 :2:2:3). After cleaving for 2 hours, the peptides may be precipitated in cold methyl-t-butyl-efher. The peptide pellets may then be dissolved in water containing 0.1% trifluoroacetic acid (TFA) and lyophilized prior to purification by C18 reverse phase HPLC. A gradient of 0-60%o acetonitrile (containing 0.1 %> TFA) in water (containing 0.1 %> TFA) may be used to elute the peptides. Following lyophilization of the pure fractions, the peptides may be characterized using electrospray mass spectrometry and by amino acid analysis.

This procedure was used to synthesize a TbM-1 peptide that contains one and a half repeats of a TbM-1 sequence. The TbM-1 peptide has the sequence GCGDRSGGNLDQIRLRRDRSGGNL (SEQ ID NO: 63).

EXAMPLE 6 USE OF REPRESENTATIVE ANTIGENS FOR SERODIAGNOSIS OF TUBERCULOSIS

This Example illustrates the diagnostic properties of several representative antigens.

Assays were performed in 96-well plates were coated with 200 ng antigen diluted to 50 μL in carbonate coating buffer, pH 9.6. The wells were coated overnight at 4°C (or 2 hours at 37°C). The plate contents were then removed and the wells were blocked for 2 hours with 200 μL of PBS/1 % BSA. After the blocking step, the wells were washed five times with PBS/0.1% Tween 20™. 50 μL sera, diluted 1 :100 in PBS/0.1% Tween 20™/0.1% BSA, was then added to each well and incubated for 30 minutes at room temperature. The plates were then washed again five times with PBS/0.1% Tween 20™.

The enzyme conjugate (horseradish peroxidase - Protein A, Zymed, San Francisco, CA) was then diluted 1 : 10,000 in PBS/0.1 % Tween 20™/0.1 % BSA, and 50 μL of the diluted conjugate was added to each well and incubated for 30 minutes at room temperature. Following incubation, the wells were washed five times with PBS/0.1% Tween 20™. 100 μL of tetramethylbenzidine peroxidase (TMB) substrate (Kirkegaard and Perry Laboratories, Gaithersburg, MD) was added, undiluted, and incubated for about 15 minutes. The reaction was stopped with the addition of 100 μL of 1 N H₂SO₄ to each well, and the plates were read at 450 nm.

Figure 4 shows the ELISA reactivity of two recombinant antigens isolated using method A in Example 3 (TbRa3 and TbRa9) with sera from M tuberculosis positive and negative patients. The reactivity of these antigens is compared to that of bacterial lysate isolated from M tuberculosis strain H37Ra (Difco, Detroit, MI). In both cases, the recombinant antigens differentiated positive from negative sera. Based on cut-off values obtained from receiver-operator curves, TbRa3 detected 56 out of 87 positive sera, and TbRa9 detected 111 out of 165 positive sera.

Figure 5 illustrates the ELISA reactivity of representative antigens isolated using method B of Example 3. The reactivity of the recombinant antigens TbH4, TbH 12, Tb38-1 and the peptide TbM-1 (as described in Example 4) is compared to that of the 38 kD antigen described by Andersen and Hansen, Infect. Immun. 57:2481-2488, 1989. Again, all of the polypeptides tested differentiated positive from negative sera. Based on cut-off values obtained from receiver-operator curves, TbH4 detected 67 out of 126 positive sera, TbH 12 detected 50 out of 125 positive sera, 38-1 detected 61 out of 101 positive sera and the TbM-1 peptide detected 25 out of 30 positive sera.

The reactivity of four antigens (TbRa3, TbRa9, TbH4 and TbH 12) with sera from a group of M. tuberculosis infected patients with differing reactivity in the acid fast stain of sputum (Smithwick and David, Tubercle 52:226, 1971) was also examined, and compared to the reactivity of M tuberculosis lysate and the 38 kD antigen. The results are presented in Table 3, below:

TABLE 3 REACTIVITY OF ANTIGENS WITH SERA FROM M. TUBERCULOSIS PATIENTS

Based on cut-off values obtained from receiver-operator curves, TbRa3 detected 23 out of 27 positive sera, TbRa9 detected 22 out of 27, TbH4 detected 18 out of 27 and TbH 12 detected 15 out of 27. If used in combination, these four antigens would have a theoretical sensitivity of 27 out of 27, indicating that these antigens should complement each other in the serological detection of M tuberculosis infection. In addition, several of the recombinant antigens detected positive sera that were not detected using the 38 kD antigen, indicating that these antigens may be complementary to the 38 kD antigen. The reactivity of the recombinant antigen TbRal 1 with sera from M. tuberculosis patients shown to be negative for the 38 kD antigen, as well as with sera from PPD positive and normal donors, was determined by ELISA as described above. The results are shown in Figure 6 which indicates that TbRal 1, while being negative with sera from PPD positive and normal donors, detected sera that were negative with the 38 kD antigen. Of the thirteen 38 kD negative sera tested, nine were positive with TbRal 1, indicating that this antigen may be reacting with a sub-group of 38 kD antigen negative sera. In contrast, in a group of 38 kD positive sera where TbRal 1 was reactive, the mean OD 450 for TbRal 1 was lower than that for the 38 kD antigen. The data indicate an inverse relationship between the presence of TbRal 1 activity and 38 kD positivity.

The antigen TbRa2A was tested in an indirect ELISA using initially 50 μl of serum at 1 :100 dilution for 30 minutes at room temperature followed by washing in PBS Tween and incubating for 30 minutes with biotinylated Protein A (Zymed, San Francisco, CA) at a 1 : 10,000 dilution. Following washing, 50 μl of streptavidin-horseradish peroxidase (Zymed) at 1 :10,000 dilution was added and the mixture incubated for 30 minutes. After washing, the assay was developed with TMB substrate as described above. The reactivity of TbRa2A with sera from M tuberculosis patients and normal donors in shown in Table 4. The mean value for reactivity of TbRa2A with sera from M tuberculosis patients was 0.444 with a standard deviation of 0.309. The mean for reactivity with sera from normal donors was 0.109 with a standard deviation of 0.029. Testing of 38 kD negative sera (Figure 7) also indicated that the TbRa2A antigen was capable of detecting sera in this category.

TABLE 4 REACTIVITY OF TBRA2A WITH SERA FROM M TUBERCULOSIS PATIENTS AND FROM NORMAL

DONORS

The reactivity of the recombinant antigen (g) (SEQ ID NO: 60) with sera from

M. tuberculosis patients and normal donors was determined by ELISA as described above.

Figure 8 shows the results of the titration of antigen (g) with four M tuberculosis positive sera that were all reactive with the 38 kD antigen and with four donor sera. All four positive sera were reactive with antigen (g).

The reactivity of the recombinant antigen TbH-29 (SEQ ID NO: 137) with sera from M. tuberculosis patients, PPD positive donors and normal donors was determined by indirect ELISA as described above. The results are shown in Figure 9. TbH-29 detected 30 out of 60 M tuberculosis sera, 2 out of 8 PPD positive sera and 2 out of 27 normal sera.

Figure 10 shows the results of ELISA tests (both direct and indirect) of the antigen TbH-33 (SEQ ID NO: 140) with sera from M tuberculosis patients and from normal donors and with a pool of sera from M. tuberculosis patients. The mean OD 450 was demonstrated to be higher with sera from M. tuberculosis patients than from normal donors, with the mean OD 450 being significantly higher in the indirect ELISA than in the direct ELISA. Figure 11 is a titration curve for the reactivity of recombinant TbH-33 with sera from M tuberculosis patients and from normal donors showing an increase in OD 450 with increasing concentration of antigen.

The reactivity of the recombinant antigens RDIF6, RDIF8 and RDIF 10 (SEQ ID NOS: 184-187, respectively) with sera from M tuberculosis patients and normal donors was determined by ELISA as described above. RDIF6 detected 6 out of 32 M tuberculosis sera and 0 out of 15 normal sera; RDIF8 detected 14 out of 32 M tuberculosis sera and 0 out of 15 normal sera; and RDIF 10 detected 4 out of 27 M tuberculosis sera and 1 out of 15 normal sera. In addition, RDIF 10 was found to detect 0 out of 5 sera from PPD-positive donors.

EXAMPLE 7

PREPARATION AND CHARACTERIZATION OF M TUBERCULOSIS FUSION PROTEINS

A fusion protein containing TbRa3, the 38 kD antigen and Tb38-1 was prepared as follows. Each of the DNA constructs TbRa3 , 38 kD and Tb38- 1 were modified by PCR in order to facilitate their fusion and the subsequent expression of the fusion protein TbRa3- 38 kD-Tb38-l. TbRa3, 38 kD and Tb38-1 DNA was used to perform PCR using the primers PDM-64 and PDM-65 (SEQ ID NO: 141 and 142), PDM-57 and PDM-58 (SEQ ID NO: 143 and 144), and PDM-69 and PDM-60 (SEQ ID NO: 145-146), respectively. In each case, the DNA amplification was performed using 10 μl 10X Pfu buffer, 2 μl 10 mM dNTPs, 2 μl each of the PCR primers at 10 μM concentration, 81.5 μl water, 1.5 μl Pfu DNA polymerase (Stratagene, La Jolla, CA) and 1 μl DNA at either 70 ng/μl (for TbRa3) or 50 ng/μl (for 38 kD and Tb38-1). For TbRa3, denaturation at 94°C was performed for 2 min, followed by 40 cycles of 96°C for 15 sec and 72°C for 1 min, and lastly by 72°C for 4 min. For 38 kD, denaturation at 96°C was performed for 2 min, followed by 40 cycles of 96°C for 30 sec, 68°C for 15 sec and 72°C for 3 min, and finally by 72°C for 4 min. For Tb38-1 denaturation at 94°C for 2 min was followed by 10 cycles of 96°C for 15 sec, 68°C for 15 sec and 72°C for 1.5 min, 30 cycles of 96°C for 15 sec, 64°C for 15 sec and 72°C for 1.5, and finally by 72°C for 4 min. The TbRa3 PCR fragment was digested with Ndel and EcoRI and cloned directly into pT7^ΛL2 IL 1 vector using Ndel and EcoRI sites. The 38 kD PCR fragment was digested with Sse8387I, treated with T4 DNA polymerase to make blunt ends and then digested with EcoRI for direct cloning into the pT7^ΛL2Ra3-l vector which was digested with Stul and EcoRI. The 38-1 PCR fragment was digested with Eco47III and EcoRI and directly subcloned into pT7^ΛL2Ra3/38kD-17 digested with the same enzymes. The whole fusion was then transferred to pET28b using Ndel and EcoRI sites. The fusion construct was confirmed by DNA sequencing.

The expression construct was transformed to BLR pLys S E. coli (Novagen, Madison, WI) and grown overnight in LB broth with kanamycin (30 μg/ml) and chloramphenicol (34 μg/ml). This culture (12 ml) was used to inoculate 500 ml 2XYT with the same antibiotics and the culture was induced with IPTG at an OD560 of 0.44 to a final concentration of 1.2 mM. Four hours post-induction, the bacteria were harvested and sonicated in 20 mM Tris (8.0), 100 mM NaCl, 0.1% DOC, 20 μg/ml Leupeptin, 20 mM PMSF followed by centrifugation at 26,000 X g. The resulting pellet was resuspended in 8 M urea, 20 mM Tris (8.0), 100 mM NaCl and bound to Pro-bond nickel resin (Invitrogen, Carlsbad, CA). The column was washed several times with the above buffer then eluted with an imidazole gradient (50 mM, 100 mM, 500 mM imidazole was added to 8 M urea, 20 mM Tris (8.0), 100 mM NaCl). The eluates containing the protein of interest were then dialzyed against 10 mM Tris (8.0). The DNA and amino acid sequences for the resulting fusion protein

(hereinafter referred to as TbRa3-38 kD-Tb38-l) are provided in SEQ ID NO: 147 and 148, respectively.

A fusion protein containing the two antigens TbH-9 and Tb38-1 (hereinafter referred to as TbH9-Tb38-l) without a hinge sequence, was prepared using a similar procedure to that described above. The DNA sequence for the TbH9-Tb38-l fusion protein is provided in SEQ ID NO: 151.

A fusion protein containing TbRa3, the antigen 38kD, Tb38-1 and DPEP was prepared as follows. Each of the DNA constructs TbRa3, 38 kD and Tb38-1 were modified by PCR and cloned into vectors essentially as described above, with the primers PDM-69 (SEQ ID NO:145 and PDM-83 (SEQ ID NO: 200) being used for amplification of the Tb38-1A fragment. Tb38-1A differs from Tb38-1 by a Dral site at the 3' end of the coding region that keeps the final amino acid intact while creating a blunt restriction site that is in frame. The TbRa3/38kD/Tb38-lA fusion was then transferred to pET28b using Ndel and EcoRI sites.

DPEP DNA was used to perform PCR using the primers PDM-84 and PDM- 85 (SEQ ID NO: 201 and 202, respectively) and 1 μl DNA at 50 ng/μl. Denaturation at 94 °C was performed for 2 min, followed by 10 cycles of 96 °C for 15 sec, 68 °C for 15 sec and 72 °C for 1.5 min; 30 cycles of 96 °C for 15 sec, 64 °C for 15 sec and 72 °C for 1.5 min; and finally by 72 °C for 4 min. The DPEP PCR fragment was digested with EcoRI and Eco72I and clones directly into the pET28Ra3/38kD/38-lA construct which was digested with Dral and EcoRI. The fusion construct was confirmed to be correct by DNA sequencing. Recombinant protein was prepared as described above. The DNA and amino acid sequences for the resulting fusion protein (hereinafter referred to as TbF-2) are provided in SEQ ID NO: 203 and 204, respectively.

EXAMPLE 8

USE OF M TUBERCULOSIS FUSION PROTEINS FOR SERODIAGNOSIS OF TUBERCULOSIS

The effectiveness of the fusion protein TbRa3-38 kD-Tb38-l, prepared as described above, in the serodiagnosis of tuberculosis infection was examined by ELISA.

The ELISA protocol was as described above in Example 6, with the fusion protein being coated at 200 ng/well. A panel of sera was chosen from a group of tuberculosis patients previously shown, either by ELISA or by western blot analysis, to react with each of the three antigens individually or in combination. Such a panel enabled the dissection of the serological reactivity of the fusion protein to determine if all three epitopes functioned with the fusion protein. As shown in Table 5, all four sera that reacted with TbRa3 only were detectable with the fusion protein. Three sera that reacted only with Tb38-1 were also detectable, as were two sear that reacted with 38 kD alone. The remaining 15 sera were all positive with the fusion protein based on a cut-off in the assay of mean negatives +3 standard deviations. This data demonstrates the functional activity of all three epitopes in the fusion protein.

TABLE 5

REACTIVITY OF TRI-PEPTIDE FUSION PROTEIN WITH SERA FROM M TUBERCULOSIS PATIENTS

The reactivity of the fusion protein TbF-2 with sera from M tuberculosis- infected patients was examined by ELISA using the protocol described above. The results of these studies (Table 6) demonstrate that all four antigens function independently in the fusion protein. TABLE 6 REACTIVITY OF TBF-2 FUSION PROTEIN WITH TB AND NORMAL SERA

One of skill in the art will appreciate that the order of the individual antigens within the fusion protein may be changed and that comparable activity would be expected provided each of the epitopes is still functionally available. In addition, truncated forms of the proteins containing active epitopes may be used in the construction of fusion proteins.

From the foregoing, it will be appreciated that, although specific embodiments of the invention have been described herein for the purpose of illustration, various modifications may be made without deviating from the spirit and scope of the invention.

SEQUENCE LISTING

(1) GENERAL INFORMATION:

(l) APPLICANTS: Reed, Steven G.

S eiky, Yasir A.W. Dillon, Davin C Campos-Neto, Antonia Houghton, Raymond Vedvick, Thomas S. Twardzik, Daniel R. Lodes, Michael J.

(n) TITLE OF INVENTION: COMPOUNDS AND METHODS FOR DIAGNOSIS OF

TUBERCULOSIS

(ill) NUMBER OF SEQUENCES: 209

(IV) CORRESPONDENCE ADDRESS:

(A) ADDRESSEE: SEED and BERRY LLP

(B) STREET: 6300 Columbia Center, 701 Fifth Avenue

(C) CITY: Seattle

(D) STATE: Washington

(E) COUNTRY: USA

(F) ZIP: 98104-7092

(v) COMPUTER READABLE FORM:

(A) MEDIUM TYPE: Floppy disk

(B) COMPUTER: IBM PC compatible

(C) OPERATING SYSTEM: PC-DOS/MS-DOS

(D) SOFTWARE: Patentln Release #1.0, Version #1.30

(vi) CURRENT APPLICATION DATA:

(A) APPLICATION NUMBER:

(B) FILING DATE: 01-OCT-1997

(C) CLASSIFICATION:

(vm) ATTORNEY/AGENT INFORMATION:

(A) NAME: Maki, David J.

(B) REGISTRATION NUMBER: 31,392

(C) REFERENCE/DOCKET NUMBER: 210121.417C7

(IX) TELECOMMUNICATION INFORMATION:

(A) TELEPHONE: (206) 622-4900

(B) TELEFAX: (206) 682-6031

(2) INFORMATION FOR SEQ ID NO:l:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 766 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:l:

CGAGGCACCG GTAGTTTGAA CCAAACGCAC AATCGACGGG CAAACGAACG GAAGAACACA 60

ACCATGAAGA TGGTGAAATC GATCGCCGCA GGTCTGACCG CCGCGGCTGC AATCGGCGCC 120

GCTGCGGCCG GTGTGACTTC GATCATGGCT GGCGGCCCGG TCGTATACCA GATGCAGCCG 180

GTCGTCTTCG GCGCGCCACT GCCGTTGGAC CCGGCATCCG CCCCTGACGT CCCGACCGCC 240

GCCCAGTTGA CCAGCCTGCT CAACAGCCTC GCCGATCCCA ACGTGTCGTT TGCGAACAAG 300

GGCAGTCTGG TCGAGGGCGG CATCGGGGGC ACCGAGGCGC GCATCGCCGA CCACAAGCTG 360

AAGAAGGCCG CCGAGCACGG GGATCTGCCG CTGTCGTTCA GCGTGACGAA CATCCAGCCG 420

GCGGCCGCCG GTTCGGCCAC CGCCGACGTT TCCGTCTCGG GTCCGAAGCT CTCGTCGCCG 480

GTCACGCAGA ACGTCACGTT CGTGAATCAA GGCGGCTGGA TGCTGTCACG CGCATCGGCG 540

ATGGAGTTGC TGCAGGCCGC AGGGNAACTG ATTGGCGGGC CGGNTTCAGC CCGCTGTTCA 600

GCTACGCCGC CCGCCTGGTG ACGCGTCCAT GTCGAACACT CGCGCGTGTA GCACGGTGCG 660

GTNTGCGCAG GGNCGCACGC ACCGCCCGGT GCAAGCCGTC CTCGAGATAG GTGGTGNCTC 720

GNCACCAGNG ANCACCCCCN NNTCGNCNNT TCTCGNTGNT GNATGA 766

(2) INFORMATION FOR SEQ ID NO : 2 :

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 752 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:2:

ATGCATCACC ATCACCATCA CGATGAAGTC ACGGTAGAGA CGACCTCCGT CTTCCGCGCA 60

GACTTCCTCA GCGAGCTGGA CGCTCCTGCG CAAGCGGGTA CGGAGAGCGC GGTCTCCGGG 120

GTGGAAGGGC TCCCGCCGGG CTCGGCGTTG CTGGTAGTCA AACGAGGCCC CAACGCCGGG 180

TCCCGGTTCC TACTCGACCA AGCCATCACG TCGGCTGGTC GGCATCCCGA CAGCGACATA 240 TTTCTCGACG ACGTGACCGT GAGCCGTCGC CATGCTGAAT TCCGGTTGGA AAACAACGAA 300

TTCAATGTCG TCGATGTCGG GAGTCTCAAC GGCACCTACG TCAACCGCGA GCCCGTGGAT 360

TCGGCGGTGC TGGCGAACGG CGACGAGGTC CAGATCGGCA AGCTCCGGTT GGTGTTCTTG 420

ACCGGACCCA AGCAAGGCGA GGATGACGGG AGTACCGGGG GCCCGTGAGC GCACCCGATA 480

GCCCCGCGCT GGCCGGGATG TCGATCGGGG CGGTCCTCCG ACCTGCTACG ACCGGATTTT 540

CCCTGATGTC CACCATCTCC AAGATTCGAT TCTTGGGAGG CTTGAGGGTC NGGGTGACCC 600

CCCCGCGGGC CTCATTCNGG GGTNTCGGCN GGTTTCACCC CNTACCNACT GCCNCCCGGN 660

TTGCNAATTC NTTCTTCNCT GCCCNNAAAG GGACCNTTAN CTTGCCGCTN GAAANGGTNA 720

TCCNGGGCCC NTCCTNGAAN CCCCNTCCCC CT 752 (2) INFORMATION FOR SEQ ID NO : 3 :

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 813 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:3:

CATATGCATC ACCATCACCA TCACACTTCT AACCGCCCAG CGCGTCGGGG GCGTCGAGCA 60

CCACGCGACA CCGGGCCCGA TCGATCTGCT AGCTTGAGTC TGGTCAGGCA TCGTCGTCAG 120

CAGCGCGATG CCCTATGTTT GTCGTCGACT CAGATATCGC GGCAATCCAA TCTCCCGCCT 180

GCGGCCGGCG GTGCTGCAAA CTACTCCCGG AGGAATTTCG ACGTGCGCAT CAAGATCTTC 240

ATGCTGGTCA CGGCTGTCGT TTTGCTCTGT TGTTCGGGTG TGGCCACGGC CGCGCCCAAG 300

ACCTACTGCG AGGAGTTGAA AGGCACCGAT ACCGGCCAGG CGTGCCAGAT TCAAATGTCC 360

GACCCGGCCT ACAACATCAA CATCAGCCTG CCCAGTTACT ACCCCGACCA GAAGTCGCTG 420

GAAAATTACA TCGCCCAGAC GCGCGACAAG TTCCTCAGCG CGGCCACATC GTCCACTCCA 480

CGCGAAGCCC CCTACGAATT GAATATCACC TCGGCCACAT ACCAGTCCGC GATACCGCCG 540

CGTGGTACGC AGGCCGTGGT GCTCAMGGTC TACCACAACG CCGGCGGCAC GCACCCAACG 600

ACCACGTACA AGGCCTTCGA TTGGGACCAG GCCTATCGCA AGCCAATCAC CTATGACACG 660

CTGTGGCAGG CTGACACCGA TCCGCTGCCA GTCGTCTTCC CCATTGTTGC AAGGTGAACT 720 GAGCAACGCA GACCGGGACA ACWGGTATCG ATAGCCGCCN AATGCCGGCT TGGAACCCNG 780 TGAAATTATC ACAACTTCGC AGTCACNAAA NAA 813

(2) INFORMATION FOR SEQ ID NO: 4:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 447 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 4:

CGGTATGAAC ACGGCCGCGT CCGATAACTT CCAGCTGTCC CAGGGTGGGC AGGGATTCGC 60

CATTCCGATC GGGCAGGCGA TGGCGATCGC GGGCCAGATC CGATCGGGTG GGGGGTCACC 120

CACCGTTCAT ATCGGGCCTA CCGCCTTCCT CGGCTTGGGT GTTGTCGACA ACAACGGCAA 180

CGGCGCACGA GTCCAACGCG TGGTCGGGAG CGCTCCGGCG GCAAGTCTCG GCATCTCCAC 240

CGGCGACGTG ATCACCGCGG TCGACGGCGC TCCGATCAAC TCGGCCACCG CGATGGCGGA 300

CGCGCTTAAC GGGCATCATC CCGGTGACGT CATCTCGGTG AACTGGCAAA CCAAGTCGGG 360

CGGCACGCGT ACAGGGAACG TGACATTGGC CGAGGGACCC CCGGCCTGAT TTCGTCGYGG 420

ATACCACCCG CCGGCCGGCC AATTGGA 447 (2) INFORMATION FOR SEQ ID NO : 5 :

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 604 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO : 5 :

GTCCCACTGC GGTCGCCGAG TATGTCGCCC AGCAAATGTC TGGCAGCCGC CCAACGGAAT 60

CCGGTGATCC GACGTCGCAG GTTGTCGAAC CCGCCGCCGC GGAAGTATCG GTCCATGCCT 120

AGCCCGGCGA CGGCGAGCGC CGGAATGGCG CGAGTGAGGA GGCGGGCAAT TTGGCGGGGC 180 CCGGCGACGG NGAGCGCCGG AATGGCGCGA GTGAGGAGGT GGNCAGTCAT GCCCAGNGTG 240

ATCCAATCAA CCTGNATTCG GNCTGNGGGN CCATTTGACA ATCGAGGTAG TGAGCGCAAA 300

TGAATGATGG AAAACGGGNG GNGACGTCCG NTGTTCTGGT GGTGNTAGGT GNCTGNCTGG 360

NGTNGNGGNT ATCAGGATGT TCTTCGNCGA AANCTGATGN CGAGGAACAG GGTGTNCCCG 420

NNANNCCNAN GGNGTCCNAN CCCNNNNTCC TCGNCGANAT CANANAGNCG NTTGATGNGA 480

NAAAAGGGTG GANCAGNNNN AANTNGNGGN CCNAANAANC NNNANNGNNG NNAGNTNGNT 540

NNNTNTTNNC ANNNNNNNTG NNGNNGNNCN NNNCAANCNN NTNNNNGNAA NNGGNTTNTT 600

NAAT 604 (2) INFORMATION FOR SEQ ID NO : 6 :

( ) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 633 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 6:

TTGCANGTCG AACCACCTCA CTAAAGGGAA CAAAAGCTNG AGCTCCACCG CGGTGGCGGC 60

CGCTCTAGAA CTAGTGKATM YYYCKGGCTG CAGSAATYCG GYACGAGCAT TAGGACAGTC 120

TAACGGTCCT GTTACGGTGA TCGAATGACC GACGACATCC TGCTGATCGA CACCGACGAA 180

CGGGTGCGAA CCCTCACCCT CAACCGGCCG CAGTCCCGYA ACGCGCTCTC GGCGGCGCTA 240

CGGGATCGGT TTTTCGCGGY GTTGGYCGAC GCCGAGGYCG ACGACGACAT CGACGTCGTC 300

ATCCTCACCG GYGCCGATCC GGTGTTCTGC GCCGGACTGG ACCTCAAGGT AGCTGGCCGG 360

GCAGACCGCG CTGCCGGACA TCTCACCGCG GTGGGCGGCC ATGACCAAGC CGGTGATCGG 420

CGCGATCAAC GGCGCCGCGG TCACCGGCGG GCTCGAACTG GCGCTGTACT GCGACATCCT 480

GATCGCCTCC GAGCACGCCC GCTTCGNCGA CACCCACGCC CGGGTGGGGC TGCTGCCCAC 540

CTGGGGACTC AGTGTGTGCT TGCCGCAAAA GGTCGGCATC GGNCTGGGCC GGTGGATGAG 600

CCTGACCGGC GACTACCTGT CCGTGACCGA CGC 633 (2) INFORMATION FOR SEQ ID NO: 7:

(l) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1362 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 7:

CGACGACGAC GGCGCCGGAG AGCGGGCGCG AACGGCGATC GACGCGGCCC TGGCCAGAGT 60

CGGCACCACC CAGGAGGGAG TCGAATCATG AAATTTGTCA ACCATATTGA GCCCGTCGCG 120

CCCCGCCGAG CCGGCGGCGC GGTCGCCGAG GTCTATGCCG AGGCCCGCCG CGAGTTCGGC 180

CGGCTGCCCG AGCCGCTCGC CATGCTGTCC CCGGACGAGG GACTGCTCAC CGCCGGCTGG 240

GCGACGTTGC GCGAGACACT GCTGGTGGGC CAGGTGCCGC GTGGCCGCAA GGAAGCCGTC 300

GCCGCCGCCG TCGCGGCCAG CCTGCGCTGC CCCTGGTGCG TCGACGCACA CACCACCATG 360

CTGTACGCGG CAGGCCAAAC CGACACCGCC GCGGCGATCT TGGCCGGCAC AGCACCTGCC 420

GCCGGTGACC CGAACGCGCC GTATGTGGCG TGGGCGGCAG GAACCGGGAC ACCGGCGGGA 480

CCGCCGGCAC CGTTCGGCCC GGATGTCGCC GCCGAATACC TGGGCACCGC GGTGCAATTC 540

CACTTCATCG CACGCCTGGT CCTGGTGCTG CTGGACGAAA CCTTCCTGCC GGGGGGCCCG 600

CGCGCCCAAC AGCTCATGCG CCGCGCCGGT GGACTGGTGT TCGCCCGCAA GGTGCGCGCG 660

GAGCATCGGC CGGGCCGCTC CACCCGCCGG CTCGAGCCGC GAACGCTGCC CGACGATCTG 720

GCATGGGCAA CACCGTCCGA GCCCATAGCA ACCGCGTTCG CCGCGCTCAG CCACCACCTG 780

GACACCGCGC CGCACCTGCC GCCACCGACT CGTCAGGTGG TCAGGCGGGT CGTGGGGTCG 840

TGGCACGGCG AGCCAATGCC GATGAGCAGT CGCTGGACGA ACGAGCACAC CGCCGAGCTG 900

CCCGCCGACC TGCACGCGCC CACCCGTCTT GCCCTGCTGA CCGGCCTGGC CCCGCATCAG 960

GTGACCGACG ACGACGTCGC CGCGGCCCGA TCCCTGCTCG ACACCGATGC GGCGCTGGTT 1020

GGCGCCCTGG CCTGGGCCGC CTTCACCGCC GCGCGGCGCA TCGGCACCTG GATCGGCGCC 1080

GCCGCCGAGG GCCAGGTGTC GCGGCAAAAC CCGACTGGGT GAGTGTGCGC GCCCTGTCGG 1140

TAGGGTGTCA TCGCTGGCCC GAGGGATCTC GCGGCGGCGA ACGGAGGTGG CGACACAGGT 1200

GGAAGCTGCG CCCACTGGCT TGCGCCCCAA CGCCGTCGTG GGCGTTCGGT TGGCCGCACT 1260

GGCCGATCAG GTCGGCGCCG GCCCTTGGCC GAAGGTCCAG CTCAACGTGC CGTCACCGAA 1320 GGACCGGACG GTCACCGGGG GTCACCCTGC GCGCCCAAGG AA 1362

(2) INFORMATION FOR SEQ ID NO : 8 :

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1458 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 8:

GCGACGACCC CGATATGCCG GGCACCGTAG CGAAAGCCGT CGCCGACGCA CTCGGGCGCG 60

GTATCGCTCC CGTTGAGGAC ATTCAGGACT GCGTGGAGGC CCGGCTGGGG GAAGCCGGTC 120

TGGATGACGT GGCCCGTGTT TACATCATCT ACCGGCAGCG GCGCGCCGAG CTGCGGACGG 180

CTAAGGCCTT GCTCGGCGTG CGGGACGAGT TAAAGCTGAG CTTGGCGGCC GTGACGGTAC 240

TGCGCGAGCG CTATCTGCTG CACGACGAGC AGGGCCGGCC GGCCGAGTCG ACCGGCGAGC 300

TGATGGACCG ATCGGCGCGC TGTGTCGCGG CGGCCGAGGA CCAGTATGAG CCGGGCTCGT 360

CGAGGCGGTG GGCCGAGCGG TTCGCCACGC TATTACGCAA CCTGGAATTC CTGCCGAATT 420

CGCCCACGTT GATGAACTCT GGCACCGACC TGGGACTGCT CGCCGGCTGT TTTGTTCTGC 480

CGATTGAGGA TTCGCTGCAA TCGATCTTTG CGACGCTGGG ACAGGCCGCC GAGCTGCAGC 540

GGGCTGGAGG CGGCACCGGA TATGCGTTCA GCCACCTGCG ACCCGCCGGG GATCGGGTGG 600

CCTCCACGGG CGGCACGGCC AGCGGACCGG TGTCGTTTCT ACGGCTGTAT GACAGTGCCG 660

CGGGTGTGGT CTCCATGGGC GGTCGCCGGC GTGGCGCCTG TATGGCTGTG CTTGATGTGT 720

CGCACCCGGA TATCTGTGAT TTCGTCACCG CCAAGGCCGA ATCCCCCAGC GAGCTCCCGC 780

ATTTCAACCT ATCGGTTGGT GTGACCGACG CGTTCCTGCG GGCCGTCGAA CGCAACGGCC 840

TACACCGGCT GGTCAATCCG CGAACCGGCA AGATCGTCGC GCGGATGCCC GCCGCCGAGC 900

TGTTCGACGC CATCTGCAAA GCCGCGCACG CCGGTGGCGA TCCCGGGCTG GTGTTTCTCG 960

ACACGATCAA TAGGGCAAAC CCGGTGCCGG GGAGAGGCCG CATCGAGGCG ACCAACCCGT 1020

GCGGGGAGGT CCCACTGCTG CCTTACGAGT CATGTAATCT CGGCTCGATC AACCTCGCCC 1080

GGATGCTCGC CGACGGTCGC GTCGACTGGG ACCGGCTCGA GGAGGTCGCC GGTGTGGCGG 1140

TGCGGTTCCT TGATGACGTC ATCGATGTCA GCCGCTACCC CTTCCCCGAA CTGGGTGAGG 1200 CGGCCCGCGC CACCCGCAAG ATCGGGCTGG GAGTCATGGG TTTGGCGGAA CTGCTTGCCG 1260

CACTGGGTAT TCCGTACGAC AGTGAAGAAG CCGTGCGGTT AGCCACCCGG CTCATGCGTC 1320

GCATACAGCA GGCGGCGCAC ACGGCATCGC GGAGGCTGGC CGAAGAGCGG GGCGCATTCC 1380

CGGCGTTCAC CGATAGCCGG TTCGCGCGGT CGGGCCCGAG GCGCAACGCA CAGGTCACCT 1440

CCGTCGCTCC GACGGGCA 1458 (2) INFORMATION FOR SEQ ID NO: 9:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 862 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 9:

ACGGTGTAAT CGTGCTGGAT CTGGAACCGC GTGGCCCGCT ACCTACCGAG ATCTACTGGC 60

GGCGCAGGGG GCTGGCCCTG GGCATCGCGG TCGTCGTAGT CGGGATCGCG GTGGCCATCG 120

TCATCGCCTT CGTCGACAGC AGCGCCGGTG CCAAACCGGT CAGCGCCGAC AAGCCGGCCT 180

CCGCCCAGAG CCATCCGGGC TCGCCGGCAC CCCAAGCACC CCAGCCGGCC GGGCAAACCG 240

AAGGTAACGC CGCCGCGGCC CCGCCGCAGG GCCAAAACCC CGAGACACCC ACGCCCACCG 300

CCGCGGTGCA GCCGCCGCCG GTGCTCAAGG AAGGGGACGA TTGCCCCGAT TCGACGCTGG 360

CCGTCAAAGG TTTGACCAAC GCGCCGCAGT ACTACGTCGG CGACCAGCCG AAGTTCACCA 420

TGGTGGTCAC CAACATCGGC CTGGTGTCCT GTAAACGCGA CGTTGGGGCC GCGGTGTTGG 480

CCGCCTACGT TTACTCGCTG GACAACAAGC GGTTGTGGTC CAACCTGGAC TGCGCGCCCT 540

CGAATGAGAC GCTGGTCAAG ACGTTTTCCC CCGGTGAGCA GGTAACGACC GCGGTGACCT 600

GGACCGGGAT GGGATCGGCG CCGCGCTGCC CATTGCCGCG GCCGGCGATC GGGCCGGGCA 660

CCTACAATCT CGTGGTACAA CTGGGCAATC TGCGCTCGCT GCCGGTTCCG TTCATCCTGA 720

ATCAGCCGCC GCCGCCGCCC GGGCCGGTAC CCGCTCCGGG TCCAGCGCAG GCGCCTCCGC 780

CGGAGTCTCC CGCGCAAGGC GGATAATTAT TGATCGCTGA TGGTCGATTC CGCCAGCTGT 840

GACAACCCCT CGCCTCGTGC CG 862 (2) INFORMATION FOR SEQ ID NO: 10:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 622 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 10:

TTGATCAGCA CCGGCAAGGC GTCACATGCC TCCCTGGGTG TGCAGGTGAC CAATGACAAA 60

GACACCCCGG GCGCCAAGAT CGTCGAAGTA GTGGCCGGTG GTGCTGCCGC GAACGCTGGA 120

GTGCCGAAGG GCGTCGTTGT CACCAAGGTC GACGACCGCC CGATCAACAG CGCGGACGCG 180

TTGGTTGCCG CCGTGCGGTC CAAAGCGCCG GGCGCCACGG TGGCGCTAAC CTTTCAGGAT 240

CCCTCGGGCG GTAGCCGCAC AGTGCAAGTC ACCCTCGGCA AGGCGGAGCA GTGATGAAGG 300

TCGCCGCGCA GTGTTCAAAG CTCGGATATA CGGTGGCACC CATGGAACAG CGTGCGGAGT 360

TGGTGGTTGG CCGGGCACTT GTCGTCGTCG TTGACGATCG CACGGCGCAC GGCGATGAAG 420

ACCACAGCGG GCCGCTTGTC ACCGAGCTGC TCACCGAGGC CGGGTTTGTT GTCGACGGCG 480

TGGTGGCGGT GTCGGCCGAC GAGGTCGAGA TCCGAAATGC GCTGAACACA GCGGTGATCG 540

GCGGGGTGGA CCTGGTGGTG TCGGTCGGCG GGACCGGNGT GACGNCTCGC GATGTCACCC 600

CGGAAGCCAC CCGNGACATT CT 622 (2) INFORMATION FOR SEQ ID NO: 11:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1200 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 11:

GGCGCAGCGG TAAGCCTGTT GGCCGCCGGC ACACTGGTGT TGACAGCATG CGGCGGTGGC 60

ACCAACAGCT CGTCGTCAGG CGCAGGCGGA ACGTCTGGGT CGGTGCACTG CGGCGGCAAG 120

AAGGAGCTCC ACTCCAGCGG CTCGACCGCA CAAGAAAATG CCATGGAGCA GTTCGTCTAT 180 GCCTACGTGC GATCGTGCCC GGGCTACACG TTGGACTACA ACGCCAACGG GTCCGGTGCC 240

GGGGTGACCC AGTTTCTCAA CAACGAAACC GATTTCGCCG GCTCGGATGT CCCGTTGAAT 300

CCGTCGACCG GTCAACCTGA CCGGTCGGCG GAGCGGTGCG GTTCCCCGGC ATGGGACCTG 360

CCGACGGTGT TCGGCCCGAT CGCGATCACC TACAATATCA AGGGCGTGAG CACGCTGAAT 420

CTTGACGGAC CCACTACCGC CAAGATTTTC AACGGCACCA TCACCGTGTG GAATGATCCA 480

CAGATCCAAG CCCTCAACTC CGGCACCGAC CTGCCGCCAA CACCGATTAG CGTTATCTTC 540

CGCAGCGACA AGTCCGGTAC GTCGGACAAC TTCCAGAAAT ACCTCGACGG TGTATCCAAC 600

GGGGCGTGGG GCAAAGGCGC CAGCGAAACG TTCAGCGGGG GCGTCGGCGT CGGCGCCAGC 660

GGGAACAACG GAACGTCGGC CCTACTGCAG ACGACCGACG GGTCGATCAC CTACAACGAG 720

TGGTCGTTTG CGGTGGGTAA GCAGTTGAAC ATGGCCCAGA TCATCACGTC GGCGGGTCCG 780

GATCCAGTGG CGATCACCAC CGAGTCGGTC GGTAAGACAA TCGCCGGGGC CAAGATCATG 840

GGACAAGGCA ACGACCTGGT ATTGGACACG TCGTCGTTCT ACAGACCCAC CCAGCCTGGC 900

TCTTACCCGA TCGTGCTGGC GACCTATGAG ATCGTCTGCT CGAAATACCC GGATGCGACG 960

ACCGGTACTG CGGTAAGGGC GTTTATGCAA GCCGCGATTG GTCCAGGCCA AGAAGGCCTG 1020

GACCAATACG GCTCCATTCC GTTGCCCAAA TCGTTCCAAG CAAAATTGGC GGCCGCGGTG 1080

AATGCTATTT CTTGACCTAG TGAAGGGAAT TCGACGGTGA GCGATGCCGT TCCGCAGGTA 1140

GGGTCGCAAT TTGGGCCGTA TCAGCTATTG CGGCTGCTGG GCCGAGGCGG GATGGGCGAG 1200

(2) INFORMATION FOR SEQ ID NO: 12:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1155 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 12:

GCAAGCAGCT GCAGGTCGTG CTGTTCGACG AACTGGGCAT GCCGAAGACC AAACGCACCA 60

AGACCGGCTA CACCACGGAT GCCGACGCGC TGCAGTCGTT GTTCGACAAG ACCGGGCATC 120

CGTTTCTGCA ACATCTGCTC GCCCACCGCG ACGTCACCCG GCTCAAGGTC ACCGTCGACG 180 GGTTGCTCCA AGCGGTGGCC GCCGACGGCC GCATCCACAC CACGTTCAAC CAGACGATCG 240

CCGCGACCGG CCGGCTCTCC TCGACCGAAC CCAACCTGCA GAACATCCCG ATCCGCACCG 300

ACGCGGGCCG GCGGATCCGG GACGCGTTCG TGGTCGGGGA CGGTTACGCC GAGTTGATGA 360

CGGCCGACTA CAGCCAGATC GAGATGCGGA TCATGGGGCA CCTGTCCGGG GACGAGGGCC 420

TCATCGAGGC GTTCAACACC GGGGAGGACC TGTATTCGTT CGTCGCGTCC CGGGTGTTCG 480

GTGTGCCCAT CGACGAGGTC ACCGGCGAGT TGCGGCGCCG GGTCAAGGCG ATGTCCTACG 540

GGCTGGTTTA CGGGTTGAGC GCCTACGGCC TGTCGCAGCA GTTGAAAATC TCCACCGAGG 600

AAGCCAACGA GCAGATGGAC GCGTATTTCG CCCGATTCGG CGGGGTGCGC GACTACCTGC 660

GCGCCGTAGT CGAGCGGGCC CGCAAGGACG GCTACACCTC GACGGTGCTG GGCCGTCGCC 720

GCTACCTGCC CGAGCTGGAC AGCAGCAACC GTCAAGTGCG GGAGGCCGCC GAGCGGGCGG 780

CGCTGAACGC GCCGATCCAG GGCAGCGCGG CCGACATCAT CAAGGTGGCC ATGATCCAGG 840

TCGACAAGGC GCTCAACGAG GCACAGCTGG CGTCGCGCAT GCTGCTGCAG GTCCACGACG 900

AGCTGCTGTT CGAAATCGCC CCCGGTGAAC GCGAGCGGGT CGAGGCCCTG GTGCGCGACA 960

AGATGGGCGG CGCTTACCCG CTCGACGTCC CGCTGGAGGT GTCGGTGGGC TACGGCCGCA 1020

GCTGGGACGC GGCGGCGCAC TGAGTGCCGA GCGTGCATCT GGGGCGGGAA TTCGGCGATT 1080

TTTCCGCCCT GAGTTCACGC TCGGCGCAAT CGGGACCGAG TTTGTCCAGC GTGTACCCGT 1140

CGAGTAGCCT CGTCA 1155 (2) INFORMATION FOR SEQ ID NO: 13:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1771 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 13:

GAGCGCCGTC TGGTGTTTGA ACGGTTTTAC CGGTCGGCAT CGGCACGGGC GTTGCCGGGT 60

TCGGGCCTCG GGTTGGCGAT CGTCAAACAG GTGGTGCTCA ACCACGGCGG ATTGCTGCGC 120

ATCGAAGACA CCGACCCAGG CGGCCAGCCC CCTGGAACGT CGATTTACGT GCTGCTCCCC 180 GGCCGTCGGA TGCCGATTCC GCAGCTTCCC GGTGCGACGG CTGGCGCTCG GAGCACGGAC 240

ATCGAGAACT CTCGGGGTTC GGCGAACGTT ATCTCAGTGG AATCTCAGTC CACGCGCGCA 300

ACCTAGTTGT GCAGTTACTG TTGAAAGCCA CACCCATGCC AGTCCACGCA TGGCCAAGTT 360

GGCCCGAGTA GTGGGCCTAG TACAGGAAGA GCAACCTAGC GACATGACGA ATCACCCACG 420

GTATTCGCCA CCGCCGCAGC AGCCGGGAAC CCCAGGTTAT GCTCAGGGGC AGCAGCAAAC 480

GTACAGCCAG CAGTTCGACT GGCGTTACCC ACCGTCCCCG CCCCCGCAGC CAACCCAGTA 540

CCGTCAACCC TACGAGGCGT TGGGTGGTAC CCGGCCGGGT CTGATACCTG GCGTGATTCC 600

GACCATGACG CCCCCTCCTG GGATGGTTCG CCAACGCCCT CGTGCAGGCA TGTTGGCCAT 660

CGGCGCGGTG ACGATAGCGG TGGTGTCCGC CGGCATCGGC GGCGCGGCCG CATCCCTGGT 720

CGGGTTCAAC CGGGCACCCG CCGGCCCCAG CGGCGGCCCA GTGGCTGCCA GCGCGGCGCC 780

AAGCATCCCC GCAGCAAACA TGCCGCCGGG GTCGGTCGAA CAGGTGGCGG CCAAGGTGGT 840

GCCCAGTGTC GTCATGTTGG AAACCGATCT GGGCCGCCAG TCGGAGGAGG GCTCCGGCAT 900

CATTCTGTCT GCCGAGGGGC TGATCTTGAC CAACAACCAC GTGATCGCGG CGGCCGCCAA 960

GCCTCCCCTG GGCAGTCCGC CGCCGAAAAC GACGGTAACC TTCTCTGACG GGCGGACCGC 1020

ACCCTTCACG GTGGTGGGGG CTGACCCCAC CAGTGATATC GCCGTCGTCC GTGTTCAGGG 1080

CGTCTCCGGG CTCACCCCGA TCTCCCTGGG TTCCTCCTCG GACCTGAGGG TCGGTCAGCC 1140

GGTGCTGGCG ATCGGGTCGC CGCTCGGTTT GGAGGGCACC GTGACCACGG GGATCGTCAG 1200

CGCTCTCAAC CGTCCAGTGT CGACGACCGG CGAGGCCGGC AACCAGAACA CCGTGCTGGA 1260

CGCCATTCAG ACCGACGCCG CGATCAACCC CGGTAACTCC GGGGGCGCGC TGGTGAACAT 1320

GAACGCTCAA CTCGTCGGAG TCAACTCGGC CATTGCCACG CTGGGCGCGG ACTCAGCCGA 1380

TGCGCAGAGC GGCTCGATCG GTCTCGGTTT TGCGATTCCA GTCGACCAGG CCAAGCGCAT 1440

CGCCGACGAG TTGATCAGCA CCGGCAAGGC GTCACATGCC TCCCTGGGTG TGCAGGTGAC 1500

CAATGACAAA GACACCCCGG GCGCCAAGAT CGTCGAAGTA GTGGCCGGTG GTGCTGCCGC 1560

GAACGCTGGA GTGCCGAAGG GCGTCGTTGT CACCAAGGTC GACGACCGCC CGATCAACAG 1620

CGCGGACGCG TTGGTTGCCG CCGTGCGGTC CAAAGCGCCG GGCGCCACGG TGGCGCTAAC 1680

CTTTCAGGAT CCCTCGGGCG GTAGCCGCAC AGTGCAAGTC ACCCTCGGCA AGGCGGAGCA 1740

GTGATGAAGG TCGCCGCGCA GTGTTCAAAG C 1771 (2) INFORMATION FOR SEQ ID NO: 14: (l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1058 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 14:

CTCCACCGCG GTGGCGGCCG CTCTAGAACT AGTGGATCCC CCGGGCTGCA GGAATTCGGC 60

ACGAGGATCC GACGTCGCAG GTTGTCGAAC CCGCCGCCGC GGAAGTATCG GTCCATGCCT 120

AGCCCGGCGA CGGCGAGCGC CGGAATGGCG CGAGTGAGGA GGCGGGCAAT TTGGCGGGGC 180

CCGGCGACGG CGAGCGCCGG AATGGCGCGA GTGAGGAGGC GGGCAGTCAT GCCCAGCGTG 240

ATCCAATCAA CCTGCATTCG GCCTGCGGGC CCATTTGACA ATCGAGGTAG TGAGCGCAAA 300

TGAATGATGG AAAACGGGCG GTGACGTCCG CTGTTCTGGT GGTGCTAGGT GCCTGCCTGG 360

CGTTGTGGCT ATCAGGATGT TCTTCGCCGA AACCTGATGC CGAGGAACAG GGTGTTCCCG 420

TGAGCCCGAC GGCGTCCGAC CCCGCGCTCC TCGCCGAGAT CAGGCAGTCG CTTGATGCGA 480

CAAAAGGGTT GACCAGCGTG CACGTAGCGG TCCGAACAAC CGGGAAAGTC GACAGCTTGC 540

TGGGTATTAC CAGTGCCGAT GTCGACGTCC GGGCCAATCC GCTCGCGGCA AAGGGCGTAT 600

GCACCTACAA CGACGAGCAG GGTGTCCCGT TTCGGGTACA AGGCGACAAC ATCTCGGTGA 660

AACTGTTCGA CGACTGGAGC AATCTCGGCT CGATTTCTGA ACTGTCAACT TCACGCGTGC 720

TCGATCCTGC CGCTGGGGTG ACGCAGCTGC TGTCCGGTGT CACGAACCTC CAAGCGCAAG 780

GTACCGAAGT GATAGACGGA ATTTCGACCA CCAAAATCAC CGGGACCATC CCCGCGAGCT 840

CTGTCAAGAT GCTTGATCCT GGCGCCAAGA GTGCAAGGCC GGCGACCGTG TGGATTGCCC 900

AGGACGGCTC GCACCACCTC GTCCGAGCGA GCATCGACCT CGGATCCGGG TCGATTCAGC 960

TCACGCAGTC GAAATGGAAC GAACCCGTCA ACGTCGACTA GGCCGAAGTT GCGTCGACGC 1020

GTTGNTCGAA ACGCCCTTGT GAACGGTGTC AACGGNAC 1058 (2) INFORMATION FOR SEQ ID NO: 15:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 542 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single (D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 15:

GAATTCGGCA CGAGAGGTGA TCGACATCAT CGGGACCAGC CCCACATCCT GGGAACAGGC 60

GGCGGCGGAG GCGGTCCAGC GGGCGCGGGA TAGCGTCGAT GACATCCGCG TCGCTCGGGT 120

CATTGAGCAG GACATGGCCG TGGACAGCGC CGGCAAGATC ACCTACCGCA TCAAGCTCGA 180

AGTGTCGTTC AAGATGAGGC CGGCGCAACC GCGCTAGCAC GGGCCGGCGA GCAAGACGCA 240

AAATCGCACG GTTTGCGGTT GATTCGTGCG ATTTTGTGTC TGCTCGCCGA GGCCTACCAG 300

GCGCGGCCCA GGTCCGCGTG CTGCCGTATC CAGGCGTGCA TCGCGATTCC GGCGGCCACG 360

CCGGAGTTAA TGCTTCGCGT CGACCCGAAC TGGGCGATCC GCCGGNGAGC TGATCGATGA 420

CCGTGGCCAG CCCGTCGATG CCCGAGTTGC CCGAGGAAAC GTGCTGCCAG GCCGGTAGGA 480

AGCGTCCGTA GGCGGCGGTG CTGACCGGCT CTGCCTGCGC CCTCAGTGCG GCCAGCGAGC 540

GG 542 (2) INFORMATION FOR SEQ ID NO: 16:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 913 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 16:

CGGTGCCGCC CGCGCCTCCG TTGCCCCCAT TGCCGCCGTC GCCGATCAGC TGCGCATCGC 60

CACCATCACC GCCTTTGCCG CCGGCACCGC CGGTGGCGCC GGGGCCGCCG ATGCCACCGC 120

TTGACCCTGG CCGCCGGCGC CGCCATTGCC ATACAGCACC CCGCCGGGGG CACCGTTACC 180

GCCGTCGCCA CCGTCGCCGC CGCTGCCGTT TCAGGCCGGG GAGGCCGAAT GAACCGCCGC 240

CAAGCCCGCC GCCGGCACCG TTGCCGCCTT TTCCGCCCGC CCCGCCGGCG CCGCCAATTG 300

CCGAACAGCC AMGCACCGTT GCCGCCAGCC CCGCCGCCGT TAACGGCGCT GCCGGGCGCC 360

GCCGCCGGAC CCGCCATTAC CGCCGTTCCC GTTCGGTGCC CCGCCGTTAC CGGCGCCGCC 420 GTTTGCCGCC AATATTCGGC GGGCACCGCC AGACCCGCCG GGGCCACCAT TGCCGCCGGG 480

CACCGAAACA ACAGCCCAAC GGTGCCGCCG GCCCCGCCGT TTGCCGCCAT CACCGGCCAT 540

TCACCGCCAG CACCGCCGTT AATGTTTATG AACCCGGTAC CGCCAGCGCG GCCCCTATTG 600

CCGGGCGCCG GAGNGCGTGC CCGCCGGCGC CGCCAACGCC CAAAAGCCCG GGGTTGCCAC 660

CGGCCCCGCC GGACCCACCG GTCCCGCCGA TCCCCCCGTT GCCGCCGGTG CCGCCGCCAT 720

TGGTGCTGCT GAAGCCGTTA GCGCCGGTTC CGCSGGTTCC GGCGGTGGCG CCNTGGCCGC 780

CGGCCCCGCC GTTGCCGTAC AGCCACCCCC CGGTGGCGCC GTTGCCGCCA TTGCCGCCAT 840

TGCCGCCGTT GCCGCCATTG CCGCCGTTCC CGCCGCCACC GCCGGNTTGG CCGCCGGCGC 900

CGCCGGCGGC CGC 913 (2) INFORMATION FOR SEQ ID NO: 17:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1872 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 17:

GACTACGTTG GTGTAGAAAA ATCCTGCCGC CCGGACCCTT AAGGCTGGGA CAATTTCTGA 60

TAGCTACCCC GACACAGGAG GTTACGGGAT GAGCAATTCG CGCCGCCGCT CACTCAGGTG 120

GTCATGGTTG CTGAGCGTGC TGGCTGCCGT CGGGCTGGGC CTGGCCACGG CGCCGGCCCA 180

GGCGGCCCCG CCGGCCTTGT CGCAGGACCG GTTCGCCGAC TTCCCCGCGC TGCCCCTCGA 240

CCCGTCCGCG ATGGTCGCCC AAGTGGCGCC ACAGGTGGTC AACATCAACA CCAAACTGGG 300

CTACAACAAC GCCGTGGGCG CCGGGACCGG CATCGTCATC GATCCCAACG GTGTCGTGCT 360

GACCAACAAC CACGTGATCG CGGGCGCCAC CGACATCAAT GCGTTCAGCG TCGGCTCCGG 420

CCAAACCTAC GGCGTCGATG TGGTCGGGTA TGACCGCACC CAGGATGTCG CGGTGCTGCA 480

GCTGCGCGGT GCCGGTGGCC TGCCGTCGGC GGCGATCGGT GGCGGCGTCG CGGTTGGTGA 540

GCCCGTCGTC GCGATGGGCA ACAGCGGTGG GCAGGGCGGA ACGCCCCGTG CGGTGCCTGG 600

CAGGGTGGTC GCGCTCGGCC AAACCGTGCA GGCGTCGGAT TCGCTGACCG GTGCCGAAGA 660 GACATTGAAC GGGTTGATCC AGTTCGATGC CGCAATCCAG CCCGGTGATT CGGGCGGGCC 720

CGTCGTCAAC GGCCTAGGAC AGGTGGTCGG TATGAACACG GCCGCGTCCG ATAACTTCCA 780

GCTGTCCCAG GGTGGGCAGG GATTCGCCAT TCCGATCGGG CAGGCGATGG CGATCGCGGG 840

CCAAATCCGA TCGGGTGGGG GGTCACCCAC CGTTCATATC GGGCCTACCG CCTTCCTCGG 900

CTTGGGTGTT GTCGACAACA ACGGCAACGG CGCACGAGTC CAACGCGTGG TCGGAAGCGC 960

TCCGGCGGCA AGTCTCGGCA TCTCCACCGG CGACGTGATC ACCGCGGTCG ACGGCGCTCC 1020

GATCAACTCG GCCACCGCGA TGGCGGACGC GCTTAACGGG CATCATCCCG GTGACGTCAT 1080

CTCGGTGAAC TGGCAAACCA AGTCGGGCGG CACGCGTACA GGGAACGTGA CATTGGCCGA 1140

GGGACCCCCG GCCTGATTTG TCGCGGATAC CACCCGCCGG CCGGCCAATT GGATTGGCGC 1200

CAGCCGTGAT TGCCGCGTGA GCCCCCGAGT TCCGTCTCCC GTGCGCGTGG CATTGTGGAA 1260

GCAATGAACG AGGCAGAACA CAGCGTTGAG CACCCTCCCG TGCAGGGCAG TTACGTCGAA 1320

GGCGGTGTGG TCGAGCATCC GGATGCCAAG GACTTCGGCA GCGCCGCCGC CCTGCCCGCC 1380

GATCCGACCT GGTTTAAGCA CGCCGTCTTC TACGAGGTGC TGGTCCGGGC GTTCTTCGAC 1440

GCCAGCGCGG ACGGTTCCGN CGATCTGCGT GGACTCATCG ATCGCCTCGA CTACCTGCAG 1500

TGGCTTGGCA TCGACTGCAT CTGTTGCCGC CGTTCCTACG ACTCACCGCT GCGCGACGGC 1560

GGTTACGACA TTCGCGACTT CTACAAGGTG CTGCCCGAAT TCGGCACCGT CGACGATTTC 1620

GTCGCCCTGG TCGACACCGC TCACCGGCGA GGTATCCGCA TCATCACCGA CCTGGTGATG 1680

AATCACACCT CGGAGTCGCA CCCCTGGTTT CAGGAGTCCC GCCGCGACCC AGACGGACCG 1740

TACGGTGACT ATTACGTGTG GAGCGACACC AGCGAGCGCT ACACCGACGC CCGGATCATC 1800

TTCGTCGACA CCGAAGAGTC GAACTGGTCA TTCGATCCTG TCCGCCGACA GTTNCTACTG 1860

GCACCGATTC TT 1872 (2) INFORMATION FOR SEQ ID NO: 18:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1482 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 18: CTTCGCCGAA ACCTGATGCC GAGGAACAGG GTGTTCCCGT GAGCCCGACG GCGTCCGACC 60

CCGCGCTCCT CGCCGAGATC AGGCAGTCGC TTGATGCGAC AAAAGGGTTG ACCAGCGTGC 120

ACGTAGCGGT CCGAACAACC GGGAAAGTCG ACAGCTTGCT GGGTATTACC AGTGCCGATG 180

TCGACGTCCG GGCCAATCCG CTCGCGGCAA AGGGCGTATG CACCTACAAC GACGAGCAGG 240

GTGTCCCGTT TCGGGTACAA GGCGACAACA TCTCGGTGAA ACTGTTCGAC GACTGGAGCA 300

ATCTCGGCTC GATTTCTGAA CTGTCAACTT CACGCGTGCT CGATCCTGCC GCTGGGGTGA 360

CGCAGCTGCT GTCCGGTGTC ACGAACCTCC AAGCGCAAGG TACCGAAGTG ATAGACGGAA 420

TTTCGACCAC CAAAATCACC GGGACCATCC CCGCGAGCTC TGTCAAGATG CTTGATCCTG 480

GCGCCAAGAG TGCAAGGCCG GCGACCGTGT GGATTGCCCA GGACGGCTCG CACCACCTCG 540

TCCGAGCGAG CATCGACCTC GGATCCGGGT CGATTCAGCT CACGCAGTCG AAATGGAACG 600

AACCCGTCAA CGTCGACTAG GCCGAAGTTG CGTCGACGCG TTGCTCGAAA CGCCCTTGTG 660

AACGGTGTCA ACGGCACCCG AAAACTGACC CCCTGACGGC ATCTGAAAAT TGACCCCCTA 720

GACCGGGCGG TTGGTGGTTA TTCTTCGGTG GTTCCGGCTG GTGGGACGCG GCCGAGGTCG 780

CGGTCTTTGA GCCGGTAGCT GTCGCCTTTG AGGGCGACGA CTTCAGCATG GTGGACGAGG 840

CGGTCGATCA TGGCGGCAGC AACGACGTCG TCGCCGCCGA AAACCTCGCC CCACCGGCCG 900

AAGGCCTTAT TGGACGTGAC GATCAAGCTG GCCCGCTCAT ACCGGGAGGA CACCAGCTGG 960

AAGAAGAGGT TGGCGGCCTC GGGCTCAAAC GGAATGTAAC CGACTTCGTC AACCACCAGG 1020

AGCGGATAGC GGCCAAACCG GGTGAGTTCG GCGTAGATGC GCCCGGCGTG GTGAGCCTCG 1080

GCGAACCGTG CTACCCATTC GGCGGCGGTG GCGAACAGCA CCCGATGACC GGCCTGACAC 1140

GCGCGTATCG CCAGGCCGAC CGCAAGATGA GTCTTCCCGG TGCCAGGCGG GGCCCAAAAA 1200

CACGACGTTA TCGCGGGCGG TGATGAAATC CAGGGTGCCC AGATGTGCGA TGGTGTCGCG 1260

TTTGAGGCCA CGAGCATGCT CAAAGTCGAA CTCTTCCAAC GACTTCCGAA CCGGGAAGCG 1320

GGCGGCGCGG ATGCGGCCCT CACCACCATG GGACTCCCGG GCTGACACTT CCCGCTGCAG 1380

GCAGGCGGCC AGGTATTCTT CGTGGCTCCA GTTCTCGGCG CGGGCGCGAT CGGCCAGCCG 1440

GGACACTGAC TCACGCAGGG TGGGAGCTTT CAATGCTCTT GT 1482

(2) INFORMATION FOR SEQ ID NO: 19:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 876 base pairs (B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 19:

GAATTCGGCA CGAGCCGGCG ATAGCTTCTG GGCCGCGGCC GACCAGATGG CTCGAGGGTT 60

CGTGCTCGGG GCCACCGCCG GGCGCACCAC CCTGACCGGT GAGGGCCTGC AACACGCCGA 120

CGGTCACTCG TTGCTGCTGG ACGCCACCAA CCCGGCGGTG GTTGCCTACG ACCCGGCCTT 180

CGCCTACGAA ATCGGCTACA TCGNGGAAAG CGGACTGGCC AGGATGTGCG GGGAGAACCC 240

GGAGAACATC TTCTTCTACA TCACCGTCTA CAACGAGCCG TACGTGCAGC CGCCGGAGCC 300

GGAGAACTTC GATCCCGAGG GCGTGCTGGG GGGTATCTAC CGNTATCACG CGGCCACCGA 360

GCAACGCACC AACAAGGNGC AGATCCTGGC CTCCGGGGTA GCGATGCCCG CGGCGCTGCG 420

GGCAGCACAG ATGCTGGCCG CCGAGTGGGA TGTCGCCGCC GACGTGTGGT CGGTGACCAG 480

TTGGGGCGAG CTAAACCGCG ACGGGGTGGT CATCGAGACC GAGAAGCTCC GCCACCCCGA 540

TCGGCCGGCG GGCGTGCCCT ACGTGACGAG AGCGCTGGAG AATGCTCGGG GCCCGGTGAT 600

CGCGGTGTCG GACTGGATGC GCGCGGTCCC CGAGCAGATC CGACCGTGGG TGCCGGGCAC 660

ATACCTCACG TTGGGCACCG ACGGGTTCGG TTTTTCCGAC ACTCGGCCCG CCGGTCGTCG 720

TTACTTCAAC ACCGACGCCG AATCCCAGGT TGGTCGCGGT TTTGGGAGGG GTTGGCCGGG 780

TCGACGGGTG AATATCGACC CATTCGGTGC CGGTCGTGGG CCGCCCGCCC AGTTACCCGG 840

ATTCGACGAA GGTGGGGGGT TGCGCCCGAN TAAGTT 876 (2) INFORMATION FOR SEQ ID NO: 20:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1021 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:20: ATCCCCCCGG GCTGCAGGAA TTCGGCACGA GAGACAAAAT TCCACGCGTT AATGCAGGAA 60 CAGATTCATA ACGAATTCAC AGCGGCACAA CAATATGTCG CGATCGCGGT TTATTTCGAC 120

AGCGAAGACC TGCCGCAGTT GGCGAAGCAT TTTTACAGCC AAGCGGTCGA GGAACGAAAC 180

CATGCAATGA TGCTCGTGCA ACACCTGCTC GACCGCGACC TTCGTGTCGA AATTCCCGGC 240

GTAGACACGG TGCGAAACCA GTTCGACAGA CCCCGCGAGG CACTGGCGCT GGCGCTCGAT 300

CAGGAACGCA CAGTCACCGA CCAGGTCGGT CGGCTGACAG CGGTGGCCCG CGACGAGGGC 360

GATTTCCTCG GCGAGCAGTT CATGCAGTGG TTCTTGCAGG AACAGATCGA AGAGGTGGCC 420

TTGATGGCAA CCCTGGTGCG GGTTGCCGAT CGGGCCGGGG CCAACCTGTT CGAGCTAGAG 480

AACTTCGTCG CACGTGAAGT GGATGTGGCG CCGGCCGCAT CAGGCGCCCC GCACGCTGCC 540

GGGGGCCGCC TCTAGATCCC TGGGGGGGAT CAGCGAGTGG TCCCGTTCGC CCGCCCGTCT 600

TCCAGCCAGG CCTTGGTGCG GCCGGGGTGG TGAGTACCAA TCCAGGCCAC CCCGACCTCC 660

CGGNAAAAGT CGATGTCCTC GTACTCATCG ACGTTCCAGG AGTACACCGC CCGGCCCTGA 720

GCTGCCGAGC GGTCAACGAG TTGCGGATAT TCCTTTAACG CAGGCAGTGA GGGTCCCACG 780

GCGGTTGGCC CGACCGCCGT GGCCGCACTG CTGGTCAGGT ATCGGGGGGT CTTGGCGAGC 840

AACAACGTCG GCAGGAGGGG TGGAGCCCGC CGGATCCGCA GACCGGGGGG GCGAAAACGA 900

CATCAACACC GCACGGGATC GATCTGCGGA GGGGGGTGCG GGAATACCGA ACCGGTGTAG 960

GAGCGCCAGC AGTTGTTTTT CCACCAGCGA AGCGTTTTCG GGTCATCGGN GGCNNTTAAG 1020

T 1021 (2) INFORMATION FOR SEQ ID NO: 21:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 321 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 21:

CGTGCCGACG AACGGAAGAA CACAACCATG AAGATGGTGA AATCGATCGC CGCAGGTCTG 60

ACCGCCGCGG CTGCAATCGG CGCCGCTGCG GCCGGTGTGA CTTCGATCAT GGCTGGCGGN 120

CCGGTCGTAT ACCAGATGCA GCCGGTCGTC TTCGGCGCGC CACTGCCGTT GGACCCGGNA 180 TCCGCCCCTG ANGTCCCGAC CGCCGCCCAG TGGACCAGNC TGCTCAACAG NCTCGNCGAT 240

CCCAACGTGT CGTTTGNGAA CAAGGGNAGT CTGGTCGAGG GNGGNATCGG NGGNANCGAG 300 GGNGNGNATC GNCGANCACA A 321

(2) INFORMATION FOR SEQ ID NO: 22:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 373 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:22:

TCTTATCGGT TCCGGTTGGC GACGGGTTTT GGGNGCGGGT GGTTAACCCG CTCGGCCAGC 60

CGATCGACGG GCGCGGAGAC GTCGACTCCG ATACTCGGCG CGCGCTGGAG CTCCAGGCGC 120

CCTCGGTGGT GNACCGGCAA GGCGTGAAGG AGCCGTTGNA GACCGGGATC AAGGCGATTG 180

ACGCGATGAC CCCGATCGGC CGCGGGCAGC GCCAGCTGAT CATCGGGGAC CGCAAGACCG 240

GCAAAAACCG CCGTCTGTGT CGGACACCAT CCTCAAACCA GCGGGAAGAA CTGGGAGTCC 300

GGTGGATCCC AAGAAGCAGG TGCGCTTGTG TATACGTTGG CCATCGGGCA AGAAGGGGAA 360

CTTACCATCG CCG 373 (2) INFORMATION FOR SEQ ID NO: 23:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 352 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 23:

GTGACGCCGT GATGGGATTC CTGGGCGGGG CCGGTCCGCT GGCGGTGGTG GATCAGCAAC 60

TGGTTACCCG GGTGCCGCAA GGCTGGTCGT TTGCTCAGGC AGCCGCTGTG CCGGTGGTGT 120

TCTTGACGGC CTGGTACGGG TTGGCCGATT TAGCCGAGAT CAAGGCGGGC GAATCGGTGC 180

TGATCCATGC CGGTACCGGC GGTGTGGGCA TGGCGGCTGT GCAGCTGGCT CGCCAGTGGG 240 GCGTGGAGGT TTTCGTCACC GCCAGCCGTG GNAAGTGGGA CACGCTGCGC GCCATNGNGT 300 TTGACGACGA NCCATATCGG NGATTCCCNC ACATNCGAAG TTCCGANGGA GA 352

(2) INFORMATION FOR SEQ ID NO: 24:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 726 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 24:

GAAATCCGCG TTCATTCCGT TCGACCAGCG GCTGGCGATA ATCGACGAAG TGATCAAGCC 60

GCGGTTCGCG GCGCTCATGG GTCACAGCGA GTAATCAGCA AGTTCTCTGG TATATCGCAC 120

CTAGCGTCCA GTTGCTTGCC AGATCGCTTT CGTACCGTCA TCGCATGTAC CGGTTCGCGT 180

GCCGCACGCT CATGCTGGCG GCGTGCATCC TGGCCACGGG TGTGGCGGGT CTCGGGGTCG 240

GCGCGCAGTC CGCAGCCCAA ACCGCGCCGG TGCCCGACTA CTACTGGTGC CCGGGGCAGC 300

CTTTCGACCC CGCATGGGGG CCCAACTGGG ATCCCTACAC CTGCCATGAC GACTTCCACC 360

GCGACAGCGA CGGCCCCGAC CACAGCCGCG ACTACCCCGG ACCCATCCTC GAAGGTCCCG 420

TGCTTGACGA TCCCGGTGCT GCGCCGCCGC CCCCGGCTGC CGGTGGCGGC GCATAGCGCT 480

CGTTGACCGG GCCGCATCAG CGAATACGCG TATAAACCCG GGCGTGCCCC CGGCAAGCTA 540

CGACCCCCGG CGGGGCAGAT TTACGCTCCC GTGCCGATGG ATCGCGCCGT CCGATGACAG 600

AAAATAGGCG ACGGTTTTGG CAACCGCTTG GAGGACGCTT GAAGGGAACC TGTCATGAAC 660

GGCGACAGCG CCTCCACCAT CGACATCGAC AAGGTTGTTA CCCGCACACC CGTTCGCCGG 720

ATCGTG 726 (2) INFORMATION FOR SEQ ID NO: 25:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 580 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:25:

CGCGACGACG ACGAACGTCG GGCCCACCAC CGCCTATGCG TTGATGCAGG CGACCGGGAT 60

GGTCGCCGAC CATATCCAAG CATGCTGGGT GCCCACTGAG CGACCTTTTG ACCAGCCGGG 120

CTGCCCGATG GCGGCCCGGT GAAGTCATTG CGCCGGGGCT TGTGCACCTG ATGAACCCGA 180

ATAGGGAACA ATAGGGGGGT GATTTGGCAG TTCAATGTCG GGTATGGCTG GAAATCCAAT 240

GGCGGGGCAT GCTCGGCGCC GACCAGGCTC GCGCAGGCGG GCCAGCCCGA ATCTGGAGGG 300

AGCACTCAAT GGCGGCGATG AAGCCCCGGA CCGGCGACGG TCCTTTGGAA GCAACTAAGG 360

AGGGGCGCGG CATTGTGATG CGAGTACCAC TTGAGGGTGG CGGTCGCCTG GTCGTCGAGC 420

TGACACCCGA CGAAGCCGCC GCACTGGGTG ACGAACTCAA AGGCGTTACT AGCTAAGACC 480

AGCCCAACGG CGAATGGTCG GCGTTACGCG CACACCTTCC GGTAGATGTC CAGTGTCTGC 540

TCGGCGATGT ATGCCCAGGA GAACTCTTGG ATACAGCGCT 580 (2) INFORMATION FOR SEQ ID NO: 26:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 160 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:26: AACGGAGGCG CCGGGGGTTT TGGCGGGGCC GGGGCGGTCG GCGGCAACGG CGGGGCCGGC 60 GGTACCGCCG GGTTGTTCGG TGTCGGCGGG GCCGGTGGGG CCGGAGGCAA CGGCATCGCC 120 GGTGTCACGG GTACGTCGGC CAGCACACCG GGTGGATCCG 160

(2) INFORMATION FOR SEQ ID NO: 27:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 272 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 27:

GACACCGATA CGATGGTGAT GTACGCCAAC GTTGTCGACA CGCTCGAGGC GTTCACGATC 60

CAGCGCACAC CCGACGGCGT GACCATCGGC GATGCGGCCC CGTTCGCGGA GGCGGCTGCC 120

AAGGCGATGG GAATCGACAA GCTGCGGGTA ATTCATACCG GAATGGACCC CGTCGTCGCT 180

GAACGCGAAC AGTGGGACGA CGGCAACAAC ACGTTGGCGT TGGCGCCCGG TGTCGTTGTC 240

GCCTACGAGC GCAACGTACA GACCAACGCC CG 272 (2) INFORMATION FOR SEQ ID NO: 28:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 317 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:28:

GCAGCCGGTG GTTCTCGGAC TATCTGCGCA CGGTGACGCA GCGCGACGTG CGCGAGCTGA 60

AGCGGATCGA GCAGACGGAT CGCCTGCCGC GGTTCATGCG CTACCTGGCC GCTATCACCG 120

CGCAGGAGCT GAACGTGGCC GAAGCGGCGC GGGTCATCGG GGTCGACGCG GGGACGATCC 180

GTTCGGATCT GGCGTGGTTC GAGACGGTCT ATCTGGTACA TCGCCTGCCC GCCTGGTCGC 240

GGAATCTGAC CGCGAAGATC AAGAAGCGGT CAAAGATCCA CGTCGTCGAC AGTGGCTTCG 300

CGGCCTGGTT GCGCGGG 317 (2) INFORMATION FOR SEQ ID NO:29:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 182 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:29: GATCGTGGAG CTGTCGATGA ACAGCGTTGC CGGACGCGCG GCGGCCAGCA CGTCGGTGTA 60 GCAGCGCCGG ACCACCTCGC CGGTGGGCAG CATGGTGATG ACCACGTCGG CCTCGGCCAC 120

CGCTTCGGGC GCGCTACGAA ACACCGCGAC ACCGTGCGCG GCGGCGCCGG ACGCCGCCGT 180

GG 182 (2) INFORMATION FOR SEQ ID NO: 30:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 308 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:30:

GATCGCGAAG TTTGGTGAGC AGGTGGTCGA CGCGAAAGTC TGGGCGCCTG CGAAGCGGGT 60

CGGCGTTCAC GAGGCGAAGA CACGCCTGTC CGAGCTGCTG CGGCTCGTCT ACGGCGGGCA 120

GAGGTTGAGA TTGCCCGCCG CGGCGAGCCG GTAGCAAAGC TTGTGCCGCT GCATCCTCAT 180

GAGACTCGGC GGTTAGGCAT TGACCATGGC GTGTACCGCG TGCCCGACGA TTTGGACGCT 240

CCGTTGTCAG ACGACGTGCT CGAACGCTTT CACCGGTGAA GCGCTACCTC ATCGACACCC 300

ACGTTTGG 308

(2) INFORMATION FOR SEQ ID NO: 31: (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 267 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 31:

CCGACGACGA GCAACTCACG TGGATGATGG TCGGCAGCGG CATTGAGGAC GGAGAGAATC 60

CGGCCGAAGC TGCCGCGCGG CAAGTGCTCA TAGTGACCGG CCGTAGAGGG CTCCCCCGAT 120

GGCACCGGAC TATTCTGGTG TGCCGCTGGC CGGTAAGAGC GGGTAAAAGA ATGTGAGGGG 180

ACACGATGAG CAATCACACC TACCGAGTGA TCGAGATCGT CGGGACCTCG CCCGACGGCG 240

TCGACGCGGC AATCCAGGGC GGTCTGG 267 (2) INFORMATION FOR SEQ ID NO: 32:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1539 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 32:

CTCGTGCCGA AAGAATGTGA GGGGACACGA TGAGCAATCA CACCTACCGA GTGATCGAGA 60

TCGTCGGGAC CTCGCCCGAC GGCGTCGACG CGGCAATCCA GGGCGGTCTG GCCCGAGCTG 120

CGCAGACCAT GCGCGCGCTG GACTGGTTCG AAGTACAGTC AATTCGAGGC CACCTGGTCG 180

ACGGAGCGGT CGCGCACTTC CAGGTGACTA TGAAAGTCGG CTTCCGCTGG AGGATTCCTG 240

AACCTTCAAG CGCGGCCGAT AACTGAGGTG CATCATTAAG CGACTTTTCC AGAACATCCT 300

GACGCGCTCG AAACGCGGTT CAGCCGACGG TGGCTCCGCC GAGGCGCTGC CTCCAAAATC 360

CCTGCGACAA TTCGTCGGCG GCGCCTACAA GGAAGTCGGT GCTGAATTCG TCGGGTATCT 420

GGTCGACCTG TGTGGGCTGC AGCCGGACGA AGCGGTGCTC GACGTCGGCT GCGGCTCGGG 480

GCGGATGGCG TTGCCGCTCA CCGGCTATCT GAACAGCGAG GGACGCTACG CCGGCTTCGA 540

TATCTCGCAG AAAGCCATCG CGTGGTGCCA GGAGCACATC ACCTCGGCGC ACCCCAACTT 600

CCAGTTCGAG GTCTCCGACA TCTACAACTC GCTGTACAAC CCGAAAGGGA AATACCAGTC 660

ACTAGACTTT CGCTTTCCAT ATCCGGATGC GTCGTTCGAT GTGGTGTTTC TTACCTCGGT 720

GTTCACCCAC ATGTTTCCGC CGGACGTGGA GCACTATCTG GACGAGATCT CCCGCGTGCT 780

GAAGCCCGGC GGACGATGCC TGTGCACGTA CTTCTTGCTC AATGACGAGT CGTTAGCCCA 840

CATCGCGGAA GGAAAGAGTG CGCACAACTT CCAGCATGAG GGACCGGGTT ATCGGACAAT 900

CCACAAGAAG CGGCCCGAAG AAGCAATCGG CTTGCCGGAG ACCTTCGTCA GGGATGTCTA 960

TGGCAAGTTC GGCCTCGCCG TGCACGAACC ATTGCACTAC GGCTCATGGA GTGGCCGGGA 1020

ACCACGCCTA AGCTTCCAGG ACATCGTCAT CGCGACCAAA ACCGCGAGCT AGGTCGGCAT 1080

CCGGGAAGCA TCGCGACACC GTGGCGCCGA GCGCCGCTGC CGGCAGGCCG ATTAGGCGGG 1140

CAGATTAGCC CGCCGCGGCT CCCGGCTCCG AGTACGGCGC CCCGAATGGC GTCACCGGCT 1200

GGTAACCACG CTTGCGCGCC TGGGCGGCGG CCTGCCGGAT CAGGTGGTAG ATGCCGACAA 1260 AGCCTGCGTG ATCGGTCATC ACCAACGGTG ACAGCAGCCG GTTGTGCACC AGCGCGAACG 1320

CCACCCCGGT CTCCGGGTCT GTCCAGCCGA TCGAGCCGCC CAAGCCCACA TGACCAAACC 1380

CCGGCATCAC GTTGCCGATC GGCATACCGT GATAGCCAAG ATGAAAATTT AAGGGCACCA 1440

ATAGATTTCG ATCCGGCAGA ACTTGCCGTC GGTTGCGGGT CAGGCCCGTG ACCAGCTCCC 1500

GCGACAAGAA CCGTATGCCG TCGATCTCGC CTCGTGCCG 1539 (2) INFORMATION FOR SEQ ID NO: 33:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 851 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 33:

CTGCAGGGTG GCGTGGATGA GCGTCACCGC GGGGCAGGCC GAGCTGACCG CCGCCCAGGT 60

CCGGGTTGCT GCGGCGGCCT ACGAGACGGC GTATGGGCTG ACGGTGCCCC CGCCGGTGAT 120

CGCCGAGAAC CGTGCTGAAC TGATGATTCT GATAGCGACC AACCTCTTGG GGCAAAACAC 180

CCCGGCGATC GCGGTCAACG AGGCCGAATA CGGCGAGATG TGGGCCCAAG ACGCCGCCGC 240

GATGTTTGGC TACGCCGCGG CGACGGCGAC GGCGACGGCG ACGTTGCTGC CGTTCGAGGA 300

GGCGCCGGAG ATGACCAGCG CGGGTGGGCT CCTCGAGCAG GCCGCCGCGG TCGAGGAGGC 360

CTCCGACACC GCCGCGGCGA ACCAGTTGAT GAACAATGTG CCCCAGGCGC TGAAACAGTT 420

GGCCCAGCCC ACGCAGGGCA CCACGCCTTC TTCCAAGCTG GGTGGCCTGT GGAAGACGGT 480

CTCGCCGCAT CGGTCGCCGA TCAGCAACAT GGTGTCGATG GCCAACAACC ACATGTCGAT 540

GACCAACTCG GGTGTGTCGA TGACCAACAC CTTGAGCTCG ATGTTGAAGG GCTTTGCTCC 600

GGCGGCGGCC GCCCAGGCCG TGCAAACCGC GGCGCAAAAC GGGGTCCGGG CGATGAGCTC 660

GCTGGGCAGC TCGCTGGGTT CTTCGGGTCT GGGCGGTGGG GTGGCCGCCA ACTTGGGTCG 720

GGCGGCCTCG GTACGGTATG GTCACCGGGA TGGCGGAAAA TATGCANAGT CTGGTCGGCG 780

GAACGGTGGT CCGGCGTAAG GTTTACCCCC GTTTTCTGGA TGCGGTGAAC TTCGTCAACG 840

GAAACAGTTA C 851 (2) INFORMATION FOR SEQ ID NO: 34:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 254 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 34:

GATCGATCGG GCGGAAATTT GGACCAGATT CGCCTCCGGC GATAACCCAA TCAATCGAAC 60

CTAGATTTAT TCCGTCCAGG GGCCCGAGTA ATGGCTCGCA GGAGAGGAAC CTTACTGCTG 120

CGGGCACCTG TCGTAGGTCC TCGATACGGC GGAAGGCGTC GACATTTTCC ACCGACACCC 180

CCATCCAAAC GTTCGAGGGC CACTCCAGCT TGTGAGCGAG GCGACGCAGT CGCAGGCTGC 240

GCTTGGTCAA GATC 254 (2) INFORMATION FOR SEQ ID NO: 35:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1227 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 35:

GATCCTGACC GAAGCGGCCG CCGCCAAGGC GAAGTCGCTG TTGGACCAGG AGGGACGGGA 60

CGATCTGGCG CTGCGGATCG CGGTTCAGCC GGGGGGGTGC GCTGGATTGC GCTATAACCT 120

TTTCTTCGAC GACCGGACGC TGGATGGTGA CCAAACCGCG GAGTTCGGTG GTGTCAGGTT 180

GATCGTGGAC CGGATGAGCG CGCCGTATGT GGAAGGCGCG TCGATCGATT TCGTCGACAC 240

TATTGAGAAG CAAGGTTCAC CATCGACAAT CCCAACGCCA CCGGCTCCTG CGCGTGCGGG 300

GATTCGTTCA ACTGATAAAA CGCTAGTACG ACCCCGCGGT GCGCAACACG TACGAGCACA 360

CCAAGACCTG ACCGCGCTGG AAAAGCAACT GAGCGATGCC TTGCACCTGA CCGCGTGGCG 420

GGCCGCCGGC GGCAGGTGTC ACCTGCATGG TGAACAGCAC CTGGGCCTGA TATTGCGACC 480

AGTACACGAT TTTGTCGATC GAGGTCACTT CGACCTGGGA GAACTGCTTG CGGAACGCGT 540 CGCTGCTCAG CTTGGCCAAG GCCTGATCGG AGCGCTTGTC GCGCACGCCG TCGTGGATAC 600

CGCACAGCGC ATTGCGAACG ATGGTGTCCA CATCGCGGTT CTCCAGCGCG TTGAGGTATC 660

CCTGAATCGC GGTTTTGGCC GGTCCCTCCG AGAATGTGCC TGCCGTGTTG GCTCCGTTGG 720

TGCGGACCCC GTATATGATC GCCGCCGTCA TAGCCGACAC CAGCGCGAGG GCTACCACAA 780

TGCCGATCAG CAGCCGCTTG TGCCGTCGCT TCGGGTAGGA CACCTGCGGC GGCACGCCGG 840

GATATGCGGC GGGCGGCAGC GCCGCGTCGT CTGCCGGTCC CGGGGCGAAG GCCGGTTCGG 900

CGGCGCCGAG GTCGTGGGGG TAGTCCAGGG CTTGGGGTTC GTGGGATGAG GGCTCGGGGT 960

ACGGCGCCGG TCCGTTGGTG CCGACACCGG GGTTCGGCGA GTGGGGACCG GGCATTGTGG 1020

TTCTCCTAGG GTGGTGGACG GGACCAGCTG CTAGGGCGAC AACCGCCCGT CGCGTCAGCC 1080

GGCAGCATCG GCAATCAGGT GAGCTCCCTA GGCAGGCTAG CGCAACAGCT GCCGTCAGCT 1140

CTCAACGCGA CGGGGCGGGC CGCGGCGCCG ATAATGTTGA AAGACTAGGC AACCTTAGGA 1200

ACGAAGGACG GAGATTTTGT GACGATC 1227 (2) INFORMATION FOR SEQ ID NO: 36:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 181 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 36:

GCGGTGTCGG CGGATCCGGC GGGTGGTTGA ACGGCAACGG CGGGGCCGGC GGGGCCGGCG 60

GGACCGGCGC TAACGGTGGT GCCGGCGGCA ACGCCTGGTT GTTCGGGGCC GGCGGGTCCG 120

GCGGNGCCGG CACCAATGGT GGNGTCGGCG GGTCCGGCGG ATTTGTCTAC GGCAACGGCG 180

G 181 (2) INFORMATION FOR SEQ ID NO: 37:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 290 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 37:

GCGGTGTCGG CGGATCCGGC GGGTGGTTGA ACGGCAACGG CGGTGTCGGC GGCCGGGGCG 60

GCGACGGCGT CTTTGCCGGT GCCGGCGGCC AGGGCGGCCT CGGTGGGCAG GGCGGCAATG 120

GCGGCGGCTC CACCGGCGGC AACGGCGGTC TTGGCGGCGC GGGCGGTGGC GGAGGCAACG 180

CCCCGGACGG CGGCTTCGGT GGCAACGGCG GTAAGGGTGG CCAGGGCGGN ATTGGCGGCG 240

GCACTCAGAG CGCGACCGGC CTCGGNGGTG ACGGCGGTGA CGGCGGTGAC 290 (2) INFORMATION FOR SEQ ID NO: 38:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 34 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 38: GATCCAGTGG CATGGNGGGT GTCAGTGGAA GCAT 34

(2) INFORMATION FOR SEQ ID NO: 39:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 155 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:39:

GATCGCTGCT CGTCCCCCCC TTGCCGCCGA CGCCACCGGT CCCACCGTTA CCGAACAAGC 60

TGGCGTGGTC GCCAGCACCC CCGGCACCGC CGACGCCGGA GTCGAACAAT GGCACCGTCG 120

TATCCCCACC ATTGCCGCCG GNCCCACCGG CACCG 155 (2) INFORMATION FOR SEQ ID NO: 40: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 53 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 40: ATGGCGTTCA CGGGGCGCCG GGGACCGGGC AGCCCGGNGG GGCCGGGGGG TGG 53

(2) INFORMATION FOR SEQ ID NO : 41 :

( ) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 132 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi ) SEQUENCE DESCRIPTION: SEQ ID NO : 41 : GATCCACCGC GGGTGCAGAC GGTGCCCGCG GCGCCACCCC GACCAGCGGC GGCAACGGCG 60 GCACCGGCGG CAACGGCGCG AACGCCACCG TCGTCGGNGG GGCCGGCGGG GCCGGCGGCA 120 AGGGCGGCAA CG 132

(2) INFORMATION FOR SEQ ID NO: 42:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 132 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 42: GATCGGCGGC CGGNACGGNC GGGGACGGCG GCAAGGGCGG NAACGGGGGC GCCGNAGCCA 60 CCNGCCAAGA ATCCTCCGNG TCCNCCAATG GCGCGAATGG CGGACAGGGC GGCAACGGCG 120 GCANCGGCGG CA 132

(2) INFORMATION FOR SEQ ID NO: 43: (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 702 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:43: CGGCACGAGG ATCGGTACCC CGCGGCATCG GCAGCTGCCG ATTCGCCGGG TTTCCCCACC 60

CGAGGAAAGC CGCTACCAGA TGGCGCTGCC GAAGTAGGGC GATCCGTTCG CGATGCCGGC 120

ATGAACGGGC GGCATCAAAT TAGTGCAGGA ACCTTTCAGT TTAGCGACGA TAATGGCTAT 180

AGCACTAAGG AGGATGATCC GATATGACGC AGTCGCAGAC CGTGACGGTG GATCAGCAAG 240

AGATTTTGAA CAGGGCCAAC GAGGTGGAGG CCCCGATGGC GGACCCACCG ACTGATGTCC 300

CCATCACACC GTGCGAACTC ACGGNGGNTA AAAACGCCGC CCAACAGNTG GTNTTGTCCG 360

CCGACAACAT GCGGGAATAC CTGGCGGCCG GTGCCAAAGA GCGGCAGCGT CTGGCGACCT 420

CGCTGCGCAA CGCGGCCAAG GNGTATGGCG AGGTTGATGA GGAGGCTGCG ACCGCGCTGG 480

ACAACGACGG CGAAGGAACT GTGCAGGCAG AATCGGCCGG GGCCGTCGGA GGGGACAGTT 540

CGGCCGAACT AACCGATACG CCGAGGGTGG CCACGGCCGG TGAACCCAAC TTCATGGATC 600

TCAAAGAAGC GGCAAGGAAG CTCGAAACGG GCGACCAAGG CGCATCGCTC GCGCACTGNG 660

GGGATGGGTG GAACACTTNC ACCCTGACGC TGCAAGGCGA CG 702 (2) INFORMATION FOR SEQ ID NO: 44:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 298 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 44:

GAAGCCGCAG CGCTGTCGGG CGACGTGGCG GTCAAAGCGG CATCGCTCGG TGGCGGTGGA 60

GGCGGCGGGG TGCCGTCGGC GCCGTTGGGA TCCGCGATCG GGGGCGCCGA ATCGGTGCGG 120

CCCGCTGGCG CTGGTGACAT TGCCGGCTTA GGCCAGGGAA GGGCCGGCGG CGGCGCCGCG 180 CTGGGCGGCG GTGGCATGGG AATGCCGATG GGTGCCGCGC ATCAGGGACA AGGGGGCGCC 240 AAGTCCAAGG GTTCTCAGCA GGAAGACGAG GCGCTCTACA CCGAGGATCC TCGTGCCG 298 (2) INFORMATION FOR SEQ ID NO:45:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1058 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 45:

CGGCACGAGG ATCGAATCGC GTCGCCGGGA GCACAGCGTC GCACTGCACC AGTGGAGGAG 60

CCATGACCTA CTCGCCGGGT AACCCCGGAT ACCCGCAAGC GCAGCCCGCA GGCTCCTACG 120

GAGGCGTCAC ACCCTCGTTC GCCCACGCCG ATGAGGGTGC GAGCAAGCTA CCGATGTACC 180

TGAACATCGC GGTGGCAGTG CTCGGTCTGG CTGCGTACTT CGCCAGCTTC GGCCCAATGT 240

TCACCCTCAG TACCGAACTC GGGGGGGGTG ATGGCGCAGT GTCCGGTGAC ACTGGGCTGC 300

CGGTCGGGGT GGCTCTGCTG GCTGCGCTGC TTGCCGGGGT GGTTCTGGTG CCTAAGGCCA 360

AGAGCCATGT GACGGTAGTT GCGGTGCTCG GGGTACTCGG CGTATTTCTG ATGGTCTCGG 420

CGACGTTTAA CAAGCCCAGC GCCTATTCGA CCGGTTGGGC ATTGTGGGTT GTGTTGGCTT 480

TCATCGTGTT CCAGGCGGTT GCGGCAGTCC TGGCGCTCTT GGTGGAGACC GGCGCTATCA 540

CCGCGCCGGC GCCGCGGCCC AAGTTCGACC CGTATGGACA GTACGGGCGG TACGGGCAGT 600

ACGGGCAGTA CGGGGTGCAG CCGGGTGGGT ACTACGGTCA GCAGGGTGCT CAGCAGGCCG 660

CGGGACTGCA GTCGCCCGGC CCGCAGCAGT CTCCGCAGCC TCCCGGATAT GGGTCGCAGT 720

ACGGCGGCTA TTCGTCCAGT CCGAGCCAAT CGGGCAGTGG ATACACTGCT CAGCCCCCGG 780

CCCAGCCGCC GGCGCAGTCC GGGTCGCAAC AATCGCACCA GGGCCCATCC ACGCCACCTA 840

CCGGCTTTCC GAGCTTCAGC CCACCACCAC CGGTCAGTGC CGGGACGGGG TCGCAGGCTG 900

GTTCGGCTCC AGTCAACTAT TCAAACCCCA GCGGGGGCGA GCAGTCGTCG TCCCCCGGGG 960

GGGCGCCGGT CTAACCGGGC GTTCCCGCGT CCGGTCGCGC GTGTGCGCGA AGAGTGAACA 1020

GGGTGTCAGC AAGCGCGGAC GATCCTCGTG CCGAATTC 1058 (2) INFORMATION FOR SEQ ID NO: 46:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 327 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO : 46 :

CGGCACGAGA GACCGATGCC GCTACCCTCG CGCAGGAGGC AGGTAATTTC GAGCGGATCT 60

CCGGCGACCT GAAAACCCAG ATCGACCAGG TGGAGTCGAC GGCAGGTTCG TTGCAGGGCC 120

AGTGGCGCGG CGCGGCGGGG ACGGCCGCCC AGGCCGCGGT GGTGCGCTTC CAAGAAGCAG 180

CCAATAAGCA GAAGCAGGAA CTCGACGAGA TCTCGACGAA TATTCGTCAG GCCGGCGTCC 240

AATACTCGAG GGCCGACGAG GAGCAGCAGC AGGCGCTGTC CTCGCAAATG GGCTTCTGAC 300

CCGCTAATAC GAAAAGAAAC GGAGCAA 327 (2) INFORMATION FOR SEQ ID NO: 47:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 170 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 7: CGGTCGCGAT GATGGCGTTG TCGAACGTGA CCGATTCTGT ACCGCCGTCG TTGAGATCAA 60 CCAACAACGT GTTGGCGTCG GCAAATGTGC CGNACCCGTG GATCTCGGTG ATCTTGTTCT 120 TCTTCATCAG GAAGTGCACA CCGGCCACCC TGCCCTCGGN TACCTTTCGG 170

(2) INFORMATION FOR SEQ ID NO: 48:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 127 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 48: GATCCGGCGG CACGGGGGGT GCCGGCGGCA GCACCGCTGG CGCTGGCGGC AACGGCGGGG 60 CCGGGGGTGG CGGCGGAACC GGTGGGTTGC TCTTCGGCAA CGGCGGTGCC GGCGGGCACG 120 GGGCCGT 127

(2) INFORMATION FOR SEQ ID NO : 49 :

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 81 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 49: CGGCGGCAAG GGCGGCACCG CCGGCAACGG GAGCGGCGCG GCCGGCGGCA ACGGCGGCAA 60 CGGCGGCTCC GGCCTCAACG G 81

(2) INFORMATION FOR SEQ ID NO: 50:

( ) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 149 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:50:

GATCAGGGCT GGCCGGCTCC GGCCAGAAGG GCGGTAACGG AGGAGCTGCC GGATTGTTTG 60

GCAACGGCGG GGCCGGNGGT GCCGGCGCGT CCAACCAAGC CGGTAACGGC GGNGCCGGCG 120 GAAACGGTGG TGCCGGTGGG CTGATCTGG 149

(2) INFORMATION FOR SEQ ID NO: 51:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 355 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single (D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 51:

CGGCACGAGA TCACACCTAC CGAGTGATCG AGATCGTCGG GACCTCGCCC GACGGTGTCG 60

ACGCGGNAAT CCAGGGCGGT CTGGCCCGAG CTGCGCAGAC CATGCGCGCG CTGGACTGGT 120

TCGAAGTACA GTCAATTCGA GGCCACCTGG TCGACGGAGC GGTCGCGCAC TTCCAGGTGA 180

CTATGAAAGT CGGCTTCCGC CTGGAGGATT CCTGAACCTT CAAGCGCGGC CGATAACTGA 240

GGTGCATCAT TAAGCGACTT TTCCAGAACA TCCTGACGCG CTCGAAACGC GGTTCAGCCG 300

ACGGTGGCTC CGCCGAGGCG CTGCCTCCAA AATCCCTGCG ACAATTCGTC GGCGG 355 (2) INFORMATION FOR SEQ ID NO: 52:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 999 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi ) SEQUENCE DESCRIPTION: SEQ ID NO: 52:

ATGCATCACC ATCACCATCA CATGCATCAG GTGGACCCCA ACTTGACACG TCGCAAGGGA 60

CGATTGGCGG CACTGGCTAT CGCGGCGATG GCCAGCGCCA GCCTGGTGAC CGTTGCGGTG 120

CCCGCGACCG CCAACGCCGA TCCGGAGCCA GCGCCCCCGG TACCCACAAC GGCCGCCTCG 180

CCGCCGTCGA CCGCTGCAGC GCCACCCGCA CCGGCGACAC CTGTTGCCCC CCCACCACCG 240

GCCGCCGCCA ACACGCCGAA TGCCCAGCCG GGCGATCCCA ACGCAGCACC TCCGCCGGCC 300

GACCCGAACG CACCGCCGCC ACCTGTCATT GCCCCAAACG CACCCCAACC TGTCCGGATC 360

GACAACCCGG TTGGAGGATT CAGCTTCGCG CTGCCTGCTG GCTGGGTGGA GTCTGACGCC 420

GCCCACTTCG ACTACGGTTC AGCACTCCTC AGCAAAACCA CCGGGGACCC GCCATTTCCC 480

GGACAGCCGC CGCCGGTGGC CAATGACACC CGTATCGTGC TCGGCCGGCT AGACCAAAAG 540

CTTTACGCCA GCGCCGAAGC CACCGACTCC AAGGCCGCGG CCCGGTTGGG CTCGGACATG 600

GGTGAGTTCT ATATGCCCTA CCCGGGCACC CGGATCAACC AGGAAACCGT CTCGCTCGAC 660 GCCAACGGGG TGTCTGGAAG CGCGTCGTAT TACGAAGTCA AGTTCAGCGA TCCGAGTAAG 720

CCGAACGGCC AGATCTGGAC GGGCGTAATC GGCTCGCCCG CGGCGAACGC ACCGGACGCC 780

GGGCCCCCTC AGCGCTGGTT TGTGGTATGG CTCGGGACCG CCAACAACCC GGTGGACAAG 840

GGCGCGGCCA AGGCGCTGGC CGAATCGATC CGGCCTTTGG TCGCCCCGCC GCCGGCGCCG 900

GCACCGGCTC CTGCAGAGCC CGCTCCGGCG CCGGCGCCGG CCGGGGAAGT CGCTCCTACC 960

CCGACGACAC CGACACCGCA GCGGACCTTA CCGGCCTGA 999 (2) INFORMATION FOR SEQ ID NO: 53:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 332 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:53:

Met His His His His His His Met His Gin Val Asp Pro Asn Leu Thr 1 5 10 15

Arg Arg Lys Gly Arg Leu Ala Ala Leu Ala lie Ala Ala Met Ala Ser 20 25 30

Ala Ser Leu Val Thr Val Ala Val Pro Ala Thr Ala Asn Ala Asp Pro 35 40 45

Glu Pro Ala Pro Pro Val Pro Thr Thr Ala Ala Ser Pro Pro Ser Thr 50 55 60

Ala Ala Ala Pro Pro Ala Pro Ala Thr Pro Val Ala Pro Pro Pro Pro 65 70 75 80

Ala Ala Ala Asn Thr Pro Asn Ala Gin Pro Gly Asp Pro Asn Ala Ala 85 90 95

Pro Pro Pro Ala Asp Pro Asn Ala Pro Pro Pro Pro Val lie Ala Pro 100 105 110

Asn Ala Pro Gin Pro Val Arg lie Asp Asn Pro Val Gly Gly Phe Ser 115 120 125

Phe Ala Leu Pro Ala Gly Trp Val Glu Ser Asp Ala Ala His Phe Asp 130 135 140

Tyr Gly Ser Ala Leu Leu Ser Lys Thr Thr Gly Asp Pro Pro Phe Pro 145 150 155 160

Gly Gin Pro Pro Pro Val Ala Asn Asp Thr Arg He Val Leu Gly Arg 165 170 175

Leu Asp Gin Lys Leu Tyr Ala Ser Ala Glu Ala Thr Asp Ser Lys Ala 180 185 190

Ala Ala Arg Leu Gly Ser Asp Met Gly Glu Phe Tyr Met Pro Tyr Pro 195 200 205

Gly Thr Arg He Asn Gin Glu Thr Val Ser Leu Asp Ala Asn Gly Val 210 215 220

Ser Gly Ser Ala Ser Tyr Tyr Glu Val Lys Phe Ser Asp Pro Ser Lys 225 230 235 240

Pro Asn Gly Gin He Trp Thr Gly Val He Gly Ser Pro Ala Ala Asn 245 250 255

Ala Pro Asp Ala Gly Pro Pro Gin Arg Trp Phe Val Val Trp Leu Gly 260 265 270

Thr Ala Asn Asn Pro Val Asp Lys Gly Ala Ala Lys Ala Leu Ala Glu 275 280 285

Ser He Arg Pro Leu Val Ala Pro Pro Pro Ala Pro Ala Pro Ala Pro 290 295 300

Ala Glu Pro Ala Pro Ala Pro Ala Pro Ala Gly Glu Val Ala Pro Thr 305 310 315 320

Pro Thr Thr Pro Thr Pro Gin Arg Thr Leu Pro Ala 325 330

(2) INFORMATION FOR SEQ ID NO: 54:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 20 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 54:

Asp Pro Val Asp Ala Val He Asn Thr Thr Xaa Asn Tyr Gly Gin Val 1 5 10 15

Val Ala Ala Leu 20 (2) INFORMATION FOR SEQ ID NO: 55:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 15 ammo acids

(B) TYPE: amino acid

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 55:

Ala Val Glu Ser Gly Met Leu Ala Leu Gly Thr Pro Ala Pro Ser 1 5 10 15

(2) INFORMATION FOR SEQ ID NO: 56:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 19 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 56:

Ala Ala Met Lys Pro Arg Thr Gly Asp Gly Pro Leu Glu Ala Ala Lys 1 5 10 15

Glu Gly Arg

(2) INFORMATION FOR SEQ ID NO: 57:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 15 ammo acids

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi ) SEQUENCE DESCRIPTION: SEQ ID NO: 57:

Tyr Tyr Trp Cys Pro Gly Gin Pro Phe Asp Pro Ala Trp Gly Pro 1 5 10 15

(2) INFORMATION FOR SEQ ID NO:58: (l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 14 ammo acids

(B) TYPE: ammo acid

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 58:

Asp He Gly Ser Glu Ser Thr Glu Asp Gin Gin Xaa Ala Val 1 5 10

(2) INFORMATION FOR SEQ ID NO: 59:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 13 ammo acids

(B) TYPE: amino acid

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:59:

Ala Glu Glu Ser He Ser Thr Xaa Glu Xaa He Val Pro 1 5 10

(2) INFORMATION FOR SEQ ID NO: 60:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 17 ammo acids

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 60:

Asp Pro Glu Pro Ala Pro Pro Val Pro Thr Ala Ala Ala Ala Pro Pro 1 5 10 15

Ala

(2) INFORMATION FOR SEQ ID NO: 61: (l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 15 ammo acids

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 61:

Ala Pro Lys Thr Tyr Xaa Glu Glu Leu Lys Gly Thr Asp Thr Gly 1 5 10 15

(2) INFORMATION FOR SEQ ID NO: 62:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 30 amino acids

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 62:

Asp Pro Ala Ser Ala Pro Asp Val Pro Thr Ala Ala Gin Gin Thr Ser 1 5 10 15

Leu Leu Asn Asn Leu Ala Asp Pro Asp Val Ser Phe Ala Asp 20 25 30

(2) INFORMATION FOR SEQ ID NO: 63:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 24 ammo acids

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 63:

Gly Cys Gly Asp Arg Ser Gly Gly Asn Leu Asp Gin He Arg Leu Arg 1 5 10 15

Arg Asp Arg Ser Gly Gly Asn Leu 20 (2) INFORMATION FOR SEQ ID NO: 64:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 187 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 64:

Thr Gly Ser Leu Asn Gin Thr His Asn Arg Arg Ala Asn Glu Arg Lys 1 5 10 15

Asn Thr Thr Met Lys Met Val Lys Ser He Ala Ala Gly Leu Thr Ala 20 25 30

Ala Ala Ala He Gly Ala Ala Ala Ala Gly Val Thr Ser He Met Ala 35 40 45

Gly Gly Pro Val Val Tyr Gin Met Gin Pro Val Val Phe Gly Ala Pro 50 55 60

Leu Pro Leu Asp Pro Ala Ser Ala Pro Asp Val Pro Thr Ala Ala Gin 65 70 75 80

Leu Thr Ser Leu Leu Asn Ser Leu Ala Asp Pro Asn Val Ser Phe Ala 85 90 95

Asn Lys Gly Ser Leu Val Glu Gly Gly He Gly Gly Thr Glu Ala Arg 100 105 110

He Ala Asp His Lys Leu Lys Lys Ala Ala Glu His Gly Asp Leu Pro 115 120 125

Leu Ser Phe Ser Val Thr Asn He Gin Pro Ala Ala Ala Gly Ser Ala 130 135 140

Thr Ala Asp Val Ser Val Ser Gly Pro Lys Leu Ser Ser Pro Val Thr 145 150 155 160

Gin Asn Val Thr Phe Val Asn Gin Gly Gly Trp Met Leu Ser Arg Ala 165 170 175

Ser Ala Met Glu Leu Leu Gin Ala Ala Gly Xaa 180 185

(2) INFORMATION FOR SEQ ID NO: 65:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 148 amino acids

(B) TYPE: amino acid (C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi ) SEQUENCE DESCRIPTION: SEQ ID NO: 65:

Asp Glu Val Thr Val Glu Thr Thr Ser Val Phe Arg Ala Asp Phe Leu 1 5 10 15

Ser Glu Leu Asp Ala Pro Ala Gin Ala Gly Thr Glu Ser Ala Val Ser 20 25 30

Gly Val Glu Gly Leu Pro Pro Gly Ser Ala Leu Leu Val Val Lys Arg 35 40 45

Gly Pro Asn Ala Gly Ser Arg Phe Leu Leu Asp Gin Ala He Thr Ser 50 55 60

Ala Gly Arg His Pro Asp Ser Asp He Phe Leu Asp Asp Val Thr Val 65 70 75 80

Ser Arg Arg His Ala Glu Phe Arg Leu Glu Asn Asn Glu Phe Asn Val 85 90 95

Val Asp Val Gly Ser Leu Asn Gly Thr Tyr Val Asn Arg Glu Pro Val 100 105 110

Asp Ser Ala Val Leu Ala Asn Gly Asp Glu Val Gin He Gly Lys Leu 115 120 125

Arg Leu Val Phe Leu Thr Gly Pro Lys Gin Gly Glu Asp Asp Gly Ser 130 135 140

Thr Gly Gly Pro 145

(2) INFORMATION FOR SEQ ID NO: 66:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 230 ammo acids

(B) TYPE: ammo acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 66:

Thr Ser Asn Arg Pro Ala Arg Arg Gly Arg Arg Ala Pro Arg Asp Thr 1 5 10 15 Gly Pro Asp Arg Ser Ala Ser Leu Ser Leu Val Arg His Arg Arg Gin 20 25 30

Gin Arg Asp Ala Leu Cys Leu Ser Ser Thr Gin He Ser Arg Gin Ser 35 40 45

Asn Leu Pro Pro Ala Ala Gly Gly Ala Ala Asn Tyr Ser Arg Arg Asn 50 55 60

Phe Asp Val Arg He Lys IJe Phe Met Leu Val Thr Ala Val Val Leu 65 70 75 80

Leu Cys Cys Ser Gly Val Ala Thr Ala Ala Pro Lys Thr Tyr Cys Glu 85 90 95

Glu Leu Lys Gly Thr Asp Thr Gly Gin Ala Cys Gin He Gin Met Ser 100 105 110

Asp Pro Ala Tyr Asn He Asn He Ser Leu Pro Ser Tyr Tyr Pro Asp 115 120 125

Gin Lys Ser Leu Glu Asn Tyr He Ala Gin Thr Arg Asp Lys Phe Leu 130 135 140

Ser Ala Ala Thr Ser Ser Thr Pro Arg Glu Ala Pro Tyr Glu Leu Asn 145 150 155 160

He Thr Ser Ala Thr Tyr Gin Ser Ala He Pro Pro Arg Gly Thr Gin 165 170 175

Ala Val Val Leu Xaa Val Tyr His Asn Ala Gly Gly Thr His Pro Thr 180 185 190

Thr Thr Tyr Lys Ala Phe Asp Trp Asp Gin Ala Tyr Arg Lys Pro He 195 200 205

Thr Tyr Asp Thr Leu Trp Gin Ala Asp Thr Asp Pro Leu Pro Val Val 210 215 220

Phe Pro He Val Ala Arg 225 230

(2) INFORMATION FOR SEQ ID NO: 67:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 132 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 67:

Thr Ala Ala Ser Asp Asn Phe Gin Leu Ser Gin Gly Gly Gin Gly Phe 1 5 10 15

Ala He Pro He Gly Gin Ala Met Ala He Ala Gly Gin He Arg Ser 20 25 30

Gly Gly Gly Ser Pro Thr Val His He Gly Pro Thr Ala Phe Leu Gly 35 40 45

Leu Gly Val Val Asp Asn Asn Gly Asn Gly Ala Arg Val Gin Arg Val 50 55 60

Val Gly Ser Ala Pro Ala Ala Ser Leu Gly He Ser Thr Gly Asp Val 65 70 75 80

He Thr Ala Val Asp Gly Ala Pro He Asn Ser Ala Thr Ala Met Ala 85 90 95

Asp Ala Leu Asn Gly His His Pro Gly Asp Val He Ser Val Asn Trp 100 105 110

Gin Thr Lys Ser Gly Gly Thr Arg Thr Gly Asn Val Thr Leu Ala Glu 115 120 125

Gly Pro Pro Ala 130

(2) INFORMATION FOR SEQ ID NO: 68:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 100 ammo acids

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 68:

Val Pro Leu Arg Ser Pro Ser Met Ser Pro Ser Lys Cys Leu Ala Ala 1 5 10 15

Ala Gin Arg Asn Pro Val He Arg Arg Arg Arg Leu Ser Asn Pro Pro 20 25 30

Pro Arg Lys Tyr Arg Ser Met Pro Ser Pro Ala Thr Ala Ser Ala Gly 35 40 45

Met Ala Arg Val Arg Arg Arg Ala He Trp Arg Gly Pro Ala Thr Xaa 50 55 60 Ser Ala Gly Met Ala Arg Val Arg Arg Trp Xaa Val Met Pro Xaa Val 65 70 75 80

He Gin Ser Thr Xaa He Arg Xaa Xaa Gly Pro Phe Asp Asn Arg Gly 85 90 95

Ser Glu Arg Lys 100

(2) INFORMATION FOR SEQ ID NO: 69:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 163 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 69:

Met Thr Asp Asp He Leu Leu He Asp Thr Asp Glu Arg Val Arg Thr 1 5 10 15

Leu Thr Leu Asn Arg Pro Gin Ser Arg Asn Ala Leu Ser Ala Ala Leu 20 25 30

Arg Asp Arg Phe Phe Ala Xaa Leu Xaa Asp Ala Glu Xaa Asp Asp Asp 35 40 45

He Asp Val Val He Leu Thr Gly Ala Asp Pro Val Phe Cys Ala Gly 50 55 60

Leu Asp Leu Lys Val Ala Gly Arg Ala Asp Arg Ala Ala Gly His Leu 65 70 75 80

Thr Ala Val Gly Gly His Asp Gin Ala Gly Asp Arg Arg Asp Gin Arg 85 90 95

Arg Arg Gly His Arg Arg Ala Arg Thr Gly Ala Val Leu Arg His Pro 100 105 110

Asp Arg Leu Arg Ala Arg Pro Leu Arg Arg His Pro Arg Pro Gly Gly 115 120 125

Ala Ala Ala His Leu Gly Thr Gin Cys Val Leu Ala Ala Lys Gly Arg 130 135 140

His Arg Xaa Gly Pro Val Asp Glu Pro Asp Arg Arg Leu Pro Val Arg 145 150 155 160

Asp Arg Arg (2) INFORMATION FOR SEQ ID NO:70:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 344 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 70:

Met Lys Phe Val Asn His He Glu Pro Val Ala Pro Arg Arg Ala Gly 1 5 10 15

Gly Ala Val Ala Glu Val Tyr Ala Glu Ala Arg Arg Glu Phe Gly Arg 20 25 30

Leu Pro Glu Pro Leu Ala Met Leu Ser Pro Asp Glu Gly Leu Leu Thr 35 40 45

Ala Gly Trp Ala Thr Leu Arg Glu Thr Leu Leu Val Gly Gin Val Pro 50 55 60

Arg Gly Arg Lys Glu Ala Val Ala Ala Ala Val Ala Ala Ser Leu Arg 65 70 75 80

Cys Pro Trp Cys Val Asp Ala His Thr Thr Met Leu Tyr Ala Ala Gly 85 90 95

Gin Thr Asp Tnr Ala Ala Ala He Leu Ala Gly Thr Ala Pro Ala Ala 100 105 110

Gly Asp Pro Asn Ala Pro Tyr Val Ala Trp Ala Ala Gly Thr Gly Thr 115 120 125

Pro Ala Gly Pro Pro Ala Pro Phe Gly Pro Asp Val Ala Ala Glu Tyr 130 135 140

Leu Gly Thr Ala Val Gin Phe His Phe He Ala Arg Leu Val Leu Val 145 150 155 160

Leu Leu Asp Glu Thr Phe Leu Pro Gly Gly Pro Arg Ala Gin Gin Leu 165 170 175

Met Arg Arg Ala Gly Gly Leu Val Phe Ala Arg Lys Val Arg Ala Glu 130 185 190

His Arg Pro Gly Arg Ser Thr Arg Arg Leu Glu Pro Arg Thr Leu Pro 195 200 205

Asp Asp Leu Ala Trp Ala Thr Pro Ser Glu Pro He Ala Thr Ala Phe 210 215 220

Ala Ala Leu Ser His His Leu Asp Thr Ala Pro His Leu Pro Pro Pro 225 230 235 240

Thr Arg Gin Val Val Arg Arg Val Val Gly Ser Trp His Gly Glu Pro 245 250 255

Met Pro Met Ser Ser Arg Trp Thr Asn Glu His Thr Ala Glu Leu Pro 260 265 270

Ala Asp Leu His Ala Pro Thr Arg Leu Ala Leu Leu Thr Gly Leu Ala 275 280 285

Pro His Gin Val Thr Asp Asp Asp Val Ala Ala Ala Arg Ser Leu Leu 290 295 300

Asp Tπr Asp Ala Ala Leu Val Gly Ala Leu Ala Trp Ala Ala Phe Thr 305 310 315 320

Ala Ala Arg Arg He Gly Thr Trp He Gly Ala Ala Ala Glu Gly Gin 325 330 335

Val Ser Arg Gin Asn Pro Thr Gly 340

(2) INFORMATION FOR SEQ ID NO: 71:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 485 amino acids

(B) TYPE: amino acid

;C) STRANDEDNESS: single (D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 71:

Asp Asp Pro Asp Met Pro Gly Thr Val Ala Lys Ala Val Ala Asp Ala 1 5 10 15

Leu Gly Arg Gly He Ala Pro Val Glu Asp He Gin Asp Cys Val Glu 20 25 30

Ala Arg Leu Gly Glu Ala Gly Leu Asp Asp Val Ala Arg Val Tyr He 35 40 45

He Tyr Arg Gin Arg Arg Ala Glu Leu Arg Thr Ala Lys Ala Leu Leu 50 55 60

Gly Val Arg Asp Glu Leu Lys Leu Ser Leu Ala Ala Val Thr Val Leu 65 70 75 80 Arg Glu Arg Tyr Leu Leu His Asp Glu Gin Gly Arg Pro Ala Glu Ser 85 90 95

Thr Gly Glu Leu Met Asp Arg Ser Ala Arg Cys Val Ala Ala Ala Glu 100 105 110

Asp Gin Tyr Glu Pro Gly Ser Ser Arg Arg Trp Ala Glu Arg Phe Ala 115 120 125

Thr Leu Leu Arg Asn Leu Glu Phe Leu Pro Asn Ser Pro Thr Leu Met 130 135 140

Asn Ser Gly Thr Asp Leu Gly Leu Leu Ala Gly Cys Phe Val Leu Pro 145 150 155 160

He Glu Asp Ser Leu Gin Ser He Phe Ala Thr Leu Gly Gin Ala Ala 165 170 175

Glu Leu Gin Arg Ala Gly Gly Gly Thr Gly Tyr Ala Phe Ser His Leu 180 185 190

Arg Pro Ala Gly Asp Arg Val Ala Ser Thr Gly Gly Thr Ala Ser Gly 195 200 205

Pro Val Ser Phe Leu Arg Leu Tyr Asp Ser Ala Ala Gly Val Val Ser 210 215 220

Met Gly Gly Arg Arg Arg Gly Ala Cys Met Ala Val Leu Asp Val Ser 225 230 235 240

His Pro Asp He Cys Asp Phe Val Thr Ala Lys Ala Glu Ser Pro Ser 245 250 255

Glu Leu Pro His Phe Asn Leu Ser Val Gly Val Thr Asp Ala Phe Leu 260 265 270

Arg Ala Val Glu Arg Asn Gly Leu His Arg Leu Val Asn Pro Arg Thr 275 280 285

Gly Lys He Val Ala Arg Met Pro Ala Ala Glu Leu Phe Asp Ala He 290 295 300

Cys Lys Ala Ala His Ala Gly Gly Asp Pro Gly Leu Val Phe Leu Asp 305 310 315 320

Thr He Asn Arg Ala Asn Pro Val Pro Gly Arg Gly Arg He Glu Ala 325 330 335

Thr Asn Pro Cys Gly Glu Val Pro Leu Leu Pro Tyr Glu Ser Cys Asn 340 345 350

Leu Gly Ser He Asn Leu Ala Arg Met Leu Ala Asp Gly Arg Val Asp 355 360 365

Trp Asp Arg Leu Glu Glu Val Ala Gly Val Ala Val Arg Phe Leu Asp 370 375 380

Asp Val He Asp Val Ser Arg Tyr Pro Phe Pro Glu Leu Gly Glu Ala 385 390 395 400

Ala Arg Ala Thr Arg Lys He Gly Leu Gly Val Met Gly Leu Ala Glu 405 410 415

Leu Leu Ala Ala Leu Gly He Pro Tyr Asp Ser Glu Glu Ala Val Arg 420 425 430

Leu Ala Thr Arg Leu Met Arg Arg He Gin Gin Ala Ala His Thr Ala 435 440 445

Ser Arg Arg Leu Ala Glu Glu Arg Gly Ala Phe Pro Ala Phe Thr Asp 450 455 460

Ser Arg Phe Ala Arg Ser Gly Pro Arg Arg Asn Ala Gin Val Thr Ser 465 470 475 480

Val Ala Pro Thr Gly 485

(2) INFORMATION FOR SEQ ID NO: 72:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 267 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 72:

Gly Val He Val Leu Asp Leu Glu Pro Arg Gly Pro Leu Pro Thr Glu 1 5 10 15

He Tyr Trp Arg Arg Arg Gly Leu Ala Leu Gly He Ala Val Val Val 20 25 30

Val Gly He Ala Val Ala He Val He Ala Phe Val Asp Ser Ser Ala 35 40 45

Gly Ala Lys Pro Val Ser Ala Asp Lys Pro Ala Ser Ala Gin Ser His 50 55 60

Pro Gly Ser Pro Ala Pro Gin Ala Pro Gin Pro Ala Gly Gin Thr Glu 65 70 75 80

Gly Asn Ala Ala Ala Ala Pro Pro Gin Gly Gin Asn Pro Glu Thr Pro 85 90 95 Thr Pro Thr Ala Ala Val Gin Pro Pro Pro Val Leu Lys Glu Gly Asp 100 105 110

Asp Cys Pro Asp Ser Thr Leu Ala Val Lys Gly Leu Thr Asn Ala Pro 115 120 125

Gin Tyr Tyr Val Gly Asp Gin Pro Lys Phe Thr Met Val Val Thr Asn 130 135 140

He Gly Leu Val Ser Cys Lys Arg Asp Val Gly Ala Ala Val Leu Ala 145 150 155 160

Ala Tyr Val Tyr Ser Leu Asp Asn Lys Arg Leu Trp Ser Asn Leu Asp 165 170 175

Cys Ala Pro Ser Asn Glu Thr Leu Val Lys Thr Phe Ser Pro Gly Glu 180 185 190

Gin Val Thr Thr Ala Val Thr Trp Thr Gly Met Gly Ser Ala Pro Arg 195 200 205

Cys Pro Leu Pro Arg Pro Ala He Gly Pro Gly Thr Tyr Asn Leu Val 210 215 220

Val Gin Leu Gly Asn Leu Arg Ser Leu Pro Val Pro Phe He Leu Asn 225 230 235 240

Gin Pro Pro Pro Pro Pro Gly Pro Val Pro Ala Pro Gly Pro Ala Gin 245 250 255

Ala Pro Pro Pro Glu Ser Pro Ala Gin Gly Gly 260 265

(2) INFORMATION FOR SEQ ID NO: 73:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 97 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:73:

Leu He Ser Thr Gly Lys Ala Ser His Ala Ser Leu Gly Val Gin Val 1 5 10 15

Thr Asn Asp Lys Asp Thr Pro Gly Ala Lys He Val Glu Val Val Ala 20 25 30

Gly Gly Ala Ala Ala Asn Ala Gly Val Pro Lys Gly Val Val Val Thr 35 40 45 Lys Val Asp Asp Arg Pro He Asn Ser Ala Asp Ala Leu Val Ala Ala 50 55 60

Val Arg Ser Lys Ala Pro Gly Ala Thr Val Ala Leu Thr Phe Gin Asp 65 70 75 80

Pro Ser Gly Gly Ser Arg Thr Val Gin Val Thr Leu Gly Lys Ala Glu 85 90 95

Gin

(2) INFORMATION FOR SEQ ID NO: 74:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 364 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:74:

Gly Ala Ala Val Ser Leu Leu Ala Ala Gly Thr Leu Val Leu Thr Ala 1 5 10 15

Cys Gly Gly Gly Thr Asn Ser Ser Ser Ser Gly Ala Gly Gly Thr Ser 20 25 30

Gly Ser Val His Cys Gly Gly Lys Lys Glu Leu His Ser Ser Gly Ser 35 40 45

Thr Ala Gin Glu Asn Ala Met Glu Gin Phe Val Tyr Ala Tyr Val Arg 50 55 60

Ser Cys Pro Gly Tyr Thr Leu Asp Tyr Asn Ala Asn Gly Ser Gly Ala 65 70 75 80

Gly Val Thr Gin Phe Leu Asn Asn Glu Thr Asp Phe Ala Gly Ser Asp 85 90 95

Val Pro Leu Asn Pro Ser Thr Gly Gin Pro Asp Arg Ser Ala Glu Arg 100 105 110

Cys Gly Ser Pro Ala Trp Asp Leu Pro Thr Val Phe Gly Pro He Ala 115 120 125

He Thr Tyr Asn He Lys Gly Val Ser Thr Leu Asn Leu Asp Gly Pro 130 135 140

Thr Thr Ala Lys He Phe Asn Gly Thr He Thr Val Trp Asn Asp Pro 145 150 155 160

Gin He Gin A] a Leu Asn Ser Gly Thr Asp Leu Pro Pro Thr Pro He 165 170 175

Ser Val He Phe Arg Ser Asp Lys Ser Gly Thr Ser Asp Asn Phe Gin 180 185 190

Lys Tyr Leu Asp Gly Val Ser Asn Gly Ala Trp Gly Lys Gly Ala Ser 195 200 205

Glu Thr Phe Ser Gly Gly Val Gly Val Gly Ala Ser Gly Asn Asn Gly 210 215 220

Thr Ser Ala Leu Leu Gin Thr Thr Asp Gly Ser He Thr Tyr Asn Glu 225 230 235 240

Trp Ser Phe Ala Val Gly Lys Gin Leu Asn Met Ala Gin He He Thr 245 250 255

Ser Ala Gly Pro Asp Pro Val Ala He Thr Thr Glu Ser Val Gly Lys 260 265 270

Thr He Ala Gly Ala Lys He Met Gly Gin Gly Asn Asp Leu Val Leu 275 280 285

Asp Thr Ser Ser Phe Tyr Arg Pro Thr Gin Pro Gly Ser Tyr Pro He 290 295 300

Val Leu Ala Thr Tyr Glu He Val Cys Ser Lys Tyr Pro Asp Ala Thr 305 310 315 320

Thr Gly Thr Ala Val Arg Ala Phe Met Gin Ala Ala He Gly Pro Gly 325 330 335

Gin Glu Gly Leu Asp Gin Tyr Gly Ser He Pro Leu Pro Lys Ser Phe 340 345 350

Gin Ala Lys Leu Ala Ala Ala Val Asn Ala He Ser 355 360

(2) INFORMATION FOR SEQ ID NO: 75:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 309 ammo acids

(B) TYPE: ammo acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 75: Gin Ala Ala Ala Gly Arg Ala Val Arg Arg Thr Gly His Ala Glu Asp 1 5 10 15

Gin Thr His Gin Asp Arg Leu His His Gly Cys Arg Arg Ala Ala Val 20 25 30

Val Val Arg Gin Asp Arg Ala Ser Val Ser Ala Thr Ser Ala Arg Pro 35 40 45

Pro Arg Arg His Pro Ala Gin Gly His Arg Arg Arg Val Ala Pro Ser 50 55 60

Gly Gly Arg Arg Arg Pro His Pro His His Val Gin Pro Asp Asp Arg 65 70 75 80

Arg Asp Arg Pro Ala Leu Leu Asp Arg Thr Gin Pro Ala Glu His Pro 85 90 95

Asp Pro His Arg Arg Gly Pro Ala Asp Pro Gly Arg Val Arg Gly Arg 100 105 110

Gly Arg Leu Arg Arg Val Asp Asp Gly Arg Leu Gin Pro Asp Arg Asp 115 120 125

Ala Asp His Gly Ala Pro Val Arg Gly Arg Gly Pro His Arg Gly Val 130 135 140

Gin His Arg Gly Gly Pro Val Phe Val Arg Arg Val Pro Gly Val Arg 145 150 155 160

Cys Ala His Arg Arg Gly His Arg Arg Val Ala Ala Pro Gly Gin Gly 165 170 175

Asp Val Leu Arg Ala Gly Leu Arg Val Glu Arg Leu Arg Pro Val Ala 180 185 190

Ala Val Glu Asn Leu His Arg Gly Ser Gin Arg Ala Asp Gly Arg Val 195 200 205

Phe Arg Pro He Arg Arg Gly Ala Arg Leu Pro Ala Arg Arg Ser Arg 210 215 220

Ala Gly Pro Gin Gly Arg Leu His Leu Asp Gly Ala Gly Pro Ser Pro 225 230 235 240

Leu Pro Ala Arg Ala Gly Gin Gin Gin Pro Ser Ser Ala Gly Gly Arg 245 250 255

Arg Ala Gly Gly Ala Glu Arg Ala Asp Pro Gly Gin Arg Gly Arg His 260 265 270

His Gin Gly Gly His Asp Pro Gly Arg Gin Gly Ala Gin Arg Gly Thr 275 280 285

Ala Gly Val Ala His Ala Ala Ala Gly Pro Arg Arg Ala Ala Val Arg 290 295 300

Asn Arg Pro Arg Arg 305

(2) INFORMATION FOR SEQ ID NO:76:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 580 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 76:

Ser Ala Val Trp Cys Leu Asn Gly Phe Thr Gly Arg His Arg His Gly 1 5 10 15

Arg Cys Arg Val Arg Ala Ser Gly Trp Arg Ser Ser Asn Arg Trp Cys 20 25 30

Ser Thr Thr Ala Asp Cys Cys Ala Ser Lys Thr Pro Thr Gin Ala Ala 35 40 45

Ser Pro Leu Glu Arg Arg Phe Thr Cys Cys Ser Pro Ala Val Gly Cys 50 55 60

Arg Phe Arg Ser Phe Pro Val Arg Arg Leu Ala Leu Gly Ala Arg Thr 65 70 75 80

Ser Arg Thr Leu Gly Val Arg Arg Thr Leu Ser Gin Trp Asn Leu Ser 85 90 95

Pro Arg Ala Gin Pro Ser Cys Ala Val Thr Val Glu Ser His Thr His 100 105 110

Ala Ser Pro Arg Met Ala Lys Leu Ala Arg Val Val Gly Leu Val Gin 115 120 125

Glu Glu Gin Pro Ser Asp Met Thr Asn His Pro Arg Tyr Ser Pro Pro 130 135 140

Pro Gin Gin Pro Gly Thr Pro Gly Tyr Ala Gin Gly Gin Gin Gin Thr 145 150 155 160

Tyr Ser Gin Gin Phe Asp Trp Arg Tyr Pro Pro Ser Pro Pro Pro Gin 165 170 175

Pro Thr Gin Tyr Arg Gin Pro Tyr Glu Ala Leu Gly Gly Thr Arg Pro 180 185 190 Gly Leu He Pro Gly Val He Pro Thr Met Thr Pro Pro Pro Gly Met 195 200 205

Val Arg Gin Arg Pro Arg Ala Gly Met Leu Ala He Gly Ala Val Thr 210 215 220

He Ala Val Val Ser Ala Gly He Gly Gly Ala Ala Ala Ser Leu Val 225 230 235 240

Gly Phe Asn Arg Ala Pro Ala Gly Pro Ser Gly Gly Pro Val Ala Ala 245 250 255

Ser Ala Ala Pro Ser He Pro Ala Ala Asn Met Pro Pro Gly Ser Val 260 265 270

Glu Gin Val Ala Ala Lys Val Val Pro Ser Val Val Met Leu Glu Thr 275 280 285

Asp Leu Gly Arg Gin Ser Glu Glu Gly Ser Gly He He Leu Ser Ala 290 295 300

Glu Gly Leu He Leu Thr Asn Asn His Val He Ala Ala Ala Ala Lys 305 310 315 320

Pro Pro Leu Gly Ser Pro Pro Pro Lys Thr Thr Val Thr Phe Ser Asp 325 330 335

Gly Arg Thr Ala Pro Phe Thr Val Val Gly Ala Asp Pro Thr Ser Asp 340 345 350

He Ala Val Val Arg Val Gin Gly Val Ser Gly Leu Thr Pro He Ser 355 360 365

Leu Gly Ser Ser Ser Asp Leu Arg Val Gly Gin Pro Val Leu Ala He 370 375 380

Gly Ser Pro Leu Gly Leu Glu Gly Thr Val Thr Thr Gly He Val Ser 385 390 395 400

Ala Leu Asn Arg Pro Val Ser Thr Thr Gly Glu Ala Gly Asn Gin Asn 405 410 415

Thr Val Leu Asp Ala He Gin Thr Asp Ala Ala He Asn Pro Gly Asn 420 425 430

Ser Gly Gly Ala Leu Val Asn Met Asn Ala Gin Leu Val Gly Val Asn 435 440 445

Ser Ala He Ala Thr Leu Gly Ala Asp Ser Ala Asp Ala Gin Ser Gly 450 455 460

Ser He Gly Leu Gly Phe Ala He Pro Val Asp Gin Ala Lys Arg He 465 470 475 480

Ala Asp Glu Leu He Ser Thr Gly Lys Ala Ser His Ala Ser Leu Gly 4 85 4 90 4 95

Val Gin Val Thr Asn Asp Lys Asp Thr Pro Gly Ala Lys He Val Glu 500 505 510

Val Val Ala Gly Gly Ala Ala Ala Asn Ala Gly Val Pro Lys Gly Val 515 520 525

Val Val Thr Lys Val Asp Asp Arg Pro He Asn Ser Ala Asp Ala Leu 530 535 540

Val Ala Ala Val Arg Ser Lys Ala Pro Gly Ala Thr Val Ala Leu Thr 545 550 555 560

Phe Gin Asp Pro Ser Gly Gly Ser Arg Thr Val Gin Val Thr Leu Gly 565 570 575

Lys Ala Glu Gin 580

(2) INFORMATION FOR SEQ ID NO: 77:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 233 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:77:

Met Asn Asp Gly Lys Arg Ala Val Thr Ser Ala Val Leu Val Val Leu 1 5 10 15

Gly Ala Cys Leu Ala Leu Trp Leu Ser Gly Cys Ser Ser Pro Lys Pro 20 25 30

Asp Ala Glu Glu Gin Gly Val Pro Val Ser Pro Thr Ala Ser Asp Pro 35 40 45

Ala Leu Leu Ala Glu He Arg Gin Ser Leu Asp Ala Thr Lys Gly Leu 50 55 60

Thr Ser Val His Val Ala Val Arg Thr Thr Gly Lys Val Asp Ser Leu 65 70 75 80

Leu Gly He Thr Ser Ala Asp Val Asp Val Arg Ala Asn Pro Leu Ala 85 90 95

Ala Lys Gly Val Cys Thr Tyr Asn Asp Glu Gin Gly Val Pro Phe Arg 100 105 110 Val Gin Gly Asp Asn He Ser Val Lys Leu Phe Asp Asp Trp Ser Asn 115 120 125

Leu Gly Ser He Ser Glu Leu Ser Thr Ser Arg Val Leu Asp Pro Ala 130 135 140

Ala Gly Val Thr Gin Leu Leu Ser Gly Val Thr Asn Leu Gin Ala Gin 145 150 155 160

Gly Thr Glu Val He Asp Gly He Ser Thr Thr Lys He Thr Gly Thr 165 170 175

He Pro Ala Ser Ser Val Lys Met Leu Asp Pro Gly Ala Lys Ser Ala 180 185 190

Arg Pro Ala Thr Val Trp He Ala Gin Asp Gly Ser His His Leu Val 195 200 205

Arg Ala Ser He Asp Leu Gly Ser Gly Ser He Gin Leu Thr Gin Ser 210 215 220

Lys Trp Asn Glu Pro Val Asn Val Asp 225 230

(2) INFORMATION FOR SEQ ID NO: 78:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 66 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 78:

Val He Asp He He Gly Thr Ser Pro Thr Ser Trp Glu Gin Ala Ala 1 5 10 15

Ala Glu Ala Val Gin Arg Ala Arg Asp Ser Val Asp Asp He Arg Val 20 25 30

Ala Arg Val He Glu Gin Asp Met Ala Val Asp Ser Ala Gly Lys He 35 40 45

Thr Tyr Arg He Lys Leu Glu Val Ser Phe Lys Met Arg Pro Ala Gin 50 55 60

Pro Arg 65

(2) INFORMATION FOR SEQ ID NO : 79 : Ii) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 69 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 79:

Val Pro Pro Ala Pro Pro Leu Pro Pro Leu Pro Pro Ser Pro He Ser 1 5 10 15

Cys Ala Ser Pro Pro Ser Pro Pro Leu Pro Pro Ala Pro Pro Val Ala 20 25 30

Pro Gly Pro Pro Met Pro Pro Leu Asp Pro Trp Pro Pro Ala Pro Pro 35 40 45

Leu Pro Tyr Ser Thr Pro Pro Gly Ala Pro Leu Pro Pro Ser Pro Pro 50 55 60

Ser Pro Pro Leu Pro 65

(2) INFORMATION FOR SEQ ID NO: 80:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 355 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 80:

Met Ser Asn Ser Arg Arg Arg Ser Leu Arg Trp Ser Trp Leu Leu Ser 1 5 10 15

Val Leu Ala Ala Val Gly Leu Gly Leu Ala Thr Ala Pro Ala Gin Ala 20 25 30

Ala Pro Pro Ala Leu Ser Gin Asp Arg Phe Ala Asp Phe Pro Ala Leu 35 40 45

Pro Leu Asp Pro Ser Ala Met Val Ala Gin Val Ala Pro Gin Val Val 50 55 60

Asn He Asn Thr Lys Leu Gly Tyr Asn Asn Ala Val Gly Ala Gly Thr 65 70 75 80 Gly He Val He Asp Pro Asn Gly Val Val Leu Thr Asn Asn His Val 85 90 95

He Ala Gly Ala Thr Asp He Asn Ala Phe Ser Val Gly Ser Gly Gin 100 105 110

Thr Tyr Gly Val Asp Val Val Gly Tyr Asp Arg Thr Gin Asp Val Ala 115 120 125

Val Leu Gin Leu Arg Gly Ala Gly Gly Leu Pro Ser Ala Ala He Gly 130 135 140

Gly Gly Val Ala Val Gly Glu Pro Val Val Ala Met Gly Asn Ser Gly 145 150 155 160

Gly Gin Gly Gly Thr Pro Arg Ala Val Pro Gly Arg Val Val Ala Leu 165 170 175

Gly Gin Thr Val Gin Ala Ser Asp Ser Leu Thr Gly Ala Glu Glu Thr 180 185 190

Leu Asn Gly Leu He Gin Phe Asp Ala Ala He Gin Pro Gly Asp Ser 195 200 205

Gly Gly Pro Val Val Asn Gly Leu Gly Gin Val Val Gly Met Asn Thr 210 215 220

Ala Ala Ser Asp Asn Phe Gin Leu Ser Gin Gly Gly Gin Gly Phe Ala 225 230 235 240

He Pro He Gly Gin Ala Met Ala He Ala Gly Gin He Arg Ser Gly 245 250 255

Gly Gly Ser Pro Thr Val His He Gly Pro Thr Ala Phe Leu Gly Leu 260 265 270

Gly Val Val Asp Asn Asn Gly Asn Gly Ala Arg Val Gin Arg Val Val 275 280 285

Gly Ser Ala Pro Ala Ala Ser Leu Gly He Ser Thr Gly Asp Val He 290 295 300

Thr Ala Val Asp Gly Ala Pro He Asn Ser Ala Thr Ala Met Ala Asp 305 310 315 320

Ala Leu Asn Gly His His Pro Gly Asp Val He Ser Val Asn Trp Gin 325 330 335

Thr Lys Ser Gly Gly Thr Arg Thr Gly Asn Val Thr Leu Ala Glu Gly 340 345 350

Pro Pro Ala 355 (2) INFORMATION FOR SEQ ID NO: 81:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 205 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 81:

Ser Pro Lys Pro Asp Ala Glu Glu Gin Gly Val Pro Val Ser Pro Thr 1 5 10 15

Ala Ser Asp Pro Ala Leu Leu Ala Glu He Arg Gin Ser Leu Asp Ala 20 25 30

Thr Lys Gly Leu Thr Ser Val His Val Ala Val Arg Thr Thr Gly Lys 35 40 45

Val Asp Ser Leu Leu Gly He Thr Ser Ala Asp Val Asp Val Arg Ala 50 55 60

Asn Pro Leu Ala Ala Lys Gly Val Cys Thr Tyr Asn Asp Glu Gin Gly 65 70 75 80

Val Pro Phe Arg Val Gin Gly Asp Asn He Ser Val Lys Leu Phe Asp 85 90 95

Asp Trp Ser Asn Leu Gly Ser He Ser Glu Leu Ser Thr Ser Arg Val 100 105 110

Leu Asp Pro Ala Ala Gly Val Thr Gin Leu Leu Ser Gly Val Thr Asn 115 120 125

Leu Gin Ala Gin Gly Thr Glu Val He Asp Gly He Ser Thr Thr Lys 130 135 140

He Thr Gly Thr He Pro Ala Ser Ser Val Lys Met Leu Asp Pro Gly 145 150 155 160

Ala Lys Ser Ala Arg Pro Ala Thr Val Trp He Ala Gin Asp Gly Ser 165 170 175

His His Leu Val Arg Ala Ser He Asp Leu Gly Ser Gly Ser He Gin 180 185 190

Leu Thr Gin Ser Lys Trp Asn Glu Pro Val Asn Val Asp 195 200 205

(2) INFORMATION FOR SEQ ID NO: 82: (l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 286 ammo acids

(B) TYPE: ammo acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 82:

Gly Asp Ser Phe Trp Ala Ala Ala Asp Gin Met Ala Arg Gly Phe Val 1 5 10 15

Leu Gly Ala Thr Ala Gly Arg Thr Thr Leu Thr Gly Glu Gly Leu Gin 20 25 30

His Ala Asp Gly His Ser Leu Leu Leu Asp Ala Thr Asn Pro Ala Val 35 40 45

Val Ala Tyr Asp Pro Ala Phe Ala Tyr Glu He Gly Tyr He Xaa Glu 50 55 60

Ser Gly Leu Ala Arg Met Cys Gly Glu Asn Pro Glu Asn He Phe Phe 65 70 75 80

Tyr He Thr Val Tyr Asn Glu Pro Tyr Val Gin Pro Pro Glu Pro Glu 85 90 95

Asn Phe Asp Pro Glu Gly Val Leu Gly Gly He Tyr Arg Tyr His Ala 100 105 110

Ala Thr Glu Gin Arg Thr Asn Lys Xaa Gin He Leu Ala Ser Gly Val 115 120 125

Ala Met Pro Ala Ala Leu Arg Ala Ala Gin Met Leu Ala Ala Glu Trp 130 135 140

Asp Val Ala Ala Asp Val Trp Ser Val Thr Ser Trp Gly Glu Leu Asn 145 150 155 160

Arg Asp Gly Val Val He Glu Thr Glu Lys Leu Arg His Pro Asp Arg 165 170 175

Pro Ala Gly Val Pro Tyr Val Thr Arg Ala Leu Glu Asn Ala Arg Gly 180 185 190

Pro Val He Ala Val Ser Asp Trp Met Arg Ala Val Pro Glu Gin He 195 200 205

Arg Pro Trp Val Pro Gly Thr Tyr Leu Thr Leu Gly Thr Asp Gly Phe 210 215 220

Gly Phe Ser Asp Thr Arg Pro Ala Gly Arg Arg Tyr Phe Asn Thr Asp 225 230 235 240

Ala Glu Ser Gin Val Gly Arg Gly Phe Gly Arg Gly Trp Pro Gly Arg 245 250 255

Arg Val Asn He Asp Pro Phe Gly Ala Gly Arg Gly Pro Pro Ala Gin 260 265 270

Leu Pro Gly Phe Asp Glu Gly Gly Gly Leu Arg Pro Xaa Lys 275 280 285

(2) INFORMATION FOR SEQ ID NO: 83:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 173 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 83:

Thr Lys Phe His Ala Leu Met Gin Glu Gin He His Asn Glu Phe Thr 1 5 10 15

Ala Ala Gin Gin Tyr Val Ala He Ala Val Tyr Phe Asp Ser Glu Asp 20 25 30

Leu Pro Gin Leu Ala Lys His Phe Tyr Ser Gin Ala Val Glu Glu Arg 35 40 45

Asn His Ala Met Met Leu Val Gin His Leu Leu Asp Arg Asp Leu Arg 50 55 60

Val Glu He Pro Gly Val Asp Thr Val Arg Asn Gin Phe Asp Arg Pro 65 70 75 80

Arg Glu Ala Leu Ala Leu Ala Leu Asp Gin Glu Arg Thr Val Thr Asp 85 90 95

Gin Val Gly Arg Leu Thr Ala Val Ala Arg Asp Glu Gly Asp Phe Leu 100 105 110

Gly Glu Gin Phe Met Gin Trp Phe Leu Gin Glu Gin He Glu Glu Val 115 120 125

Ala Leu Met Ala Thr Leu Val Arg Val Ala Asp Arg Ala Gly Ala Asn 130 135 140

Leu Phe Glu Leu Glu Asn Phe Val Ala Arg Glu Val Asp Val Ala Pro 145 150 155 160 Ala Ala Ser Gly Ala Pro His Ala Ala Gly Gly Arg Leu 165 170

(2) INFORMATION FOR SEQ ID NO: 84:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 107 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 84:

Arg Ala Asp Glu Arg Lys Asn Thr Thr Met Lys Met Val Lys Ser He 1 5 10 15

Ala Ala Gly Leu Thr Ala Ala Ala Ala He Gly Ala Ala Ala Ala Gly 20 25 30

Val Thr Ser He Met Ala Gly Gly Pro Val Val Tyr Gin Met Gin Pro 35 40 45

Val Val Phe Gly Ala Pro Leu Pro Leu Asp Pro Xaa Ser Ala Pro Xaa 50 55 60

Val Pro Thr Ala Ala Gin Trp Thr Xaa Leu Leu Asn Xaa Leu Xaa Asp 65 70 75 80

Pro Asn Val Ser Phe Xaa Asn Lys Gly Ser Leu Val Glu Gly Gly He 85 90 95

Gly Gly Xaa Glu Gly Xaa Xaa Arg Arg Xaa Gin 100 105

(2) INFORMATION FOR SEQ ID NO: 85: (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 125 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 85:

Val Leu Ser Val Pro Val Gly Asp Gly Phe Trp Xaa Arg Val Val Asn 1 5 10 15

Pro Leu Gly Gin Pro He Asp Gly Arg Gly Asp Val Asp Ser Asp Thr 20 25 30

Arg Arg Ala Leu Glu Leu Gin Ala Pro Ser Val Val Xaa Arg Gin Gly 35 40 45

Val Lys Glu Pro Leu Xaa Thr Gly He Lys Ala He Asp Ala Met Thr 50 55 60

Pro He Gly Arg Gly Gin Arg Gin Leu He He Gly Asp Arg Lys Thr 65 70 75 80

Gly Lys Asn Arg Arg Leu Cys Arg Thr Pro Ser Ser Asn Gin Arg Glu 85 90 95

Glu Leu Gly Val Arg Trp He Pro Arg Ser Arg Cys Ala Cys Val Tyr 100 105 110

Val Gly His Arg Ala Arg Arg Gly Thr Tyr His Arg Arg 115 120 125

(2) INFORMATION FOR SEQ ID NO: 86:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 117 ammo acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 86:

Cys Asp Ala Val Met Gly Phe Leu Gly Gly Ala Gly Pro Leu Ala Val 1 5 10 15

Val Asp Gin Gin Leu Val Thr Arg Val Pro Gin Gly Trp Ser Phe Ala 20 25 30

Gin Ala Ala Ala Val Pro Val Val Phe Leu Thr Ala Trp Tyr Gly Leu 35 40 45

Ala Asp Leu Ala Glu He Lys Ala Gly Glu Ser Val Leu He His Ala 50 55 60

Gly Thr Gly Gly Val Gly Met Ala Ala Val Gin Leu Ala Arg Gin Trp 65 70 75 80

Gly Val Glu Val Phe Val Thr Ala Ser Arg Gly Lys Trp Asp Thr Leu 85 90 95

Arg Ala Xaa Xaa Phe Asp Asp Xaa Pro Tyr Arg Xaa Phe Pro His Xaa 100 105 110 Arg Ser Ser Xaa Gly 115

(2) INFORMATION FOR SEQ ID NO: 87:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 103 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 87:

Met Tyr Arg Phe Ala Cys Arg Thr Leu Met Leu Ala Ala Cys He Leu 1 5 10 15

Ala Thr Gly Val Ala Gly Leu Gly Val Gly Ala Gin Ser Ala Ala Gin 20 25 30

Thr Ala Pro Val Pro Asp Tyr Tyr Trp Cys Pro Gly Gin Pro Phe Asp 35 40 45

Pro Ala Trp Gly Pro Asn Trp Asp Pro Tyr Thr Cys His Asp Asp Phe 50 55 60

His Arg Asp Ser Asp Gly Pro Asp His Ser Arg Asp Tyr Pro Gly Pro 65 70 75 80

He Leu Glu Gly Pro Val Leu Asp Asp Pro Gly Ala Ala Pro Pro Pro 85 90 95

Pro Ala Ala Gly Gly Gly Ala 100

(2) INFORMATION FOR SEQ ID NO: 88:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 88 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

( xi ) SEQUENCE DESCRI PTION : SEQ I D NO : 88 :

Val Gin Cys Arg Val Trp Leu Glu He Gin Trp Arg Gly Met Leu Gly 1 5 10 15 Ala Asp Gin Ala Arg Ala Gly Gly Pro Ala Arg He Trp Arg Glu His 20 25 30

Ser Met Ala Ala Met Lys Pro Arg Thr Gly Asp Gly Pro Leu Glu Ala 35 40 45

Thr Lys Glu Gly Arg Gly He Val Met Arg Val Pro Leu Glu Gly Gly 50 55 60

Gly Arg Leu Val Val Glu Leu Thr Pro Asp Glu Ala Ala Ala Leu Gly 65 70 75 80

Asp Glu Leu Lys Gly Val Thr Ser 85

(2) INFORMATION FOR SEQ ID NO: 89:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 95 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO : 89 :

Thr Asp Ala Ala Thr Leu Ala Gin Glu Ala Gly Asn Phe Glu Arg He 1 5 10 15

Ser Gly Asp Leu Lys Thr Gin He Asp Gin Val Glu Ser Thr Ala Gly 20 25 30

Ser Leu Gin Gly Gin Trp Arg Gly Ala Ala Gly Thr Ala Ala Gin Ala 35 40 45

Ala Val Val Arg Phe Gin Glu Ala Ala Asn Lys Gin Lys Gin Glu Leu 50 55 60

Asp Glu He Ser Thr Asn He Arg Gin Ala Gly Val Gin Tyr Ser Arg 65 70 75 80

Ala Asp Glu Glu Gin Gin Gin Ala Leu Ser Ser Gin Met Gly Phe 85 90 95

(2) INFORMATION FOR SEQ ID NO: 90:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 166 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 90:

Met Thr Gin Ser Gin Thr Val Thr Val Asp Gin Gin Glu He Leu Asn 1 5 10 15

Arg Ala Asn Glu Val Glu Ala Pro Met Ala Asp Pro Pro Thr Asp Val 20 25 30

Pro He Thr Pro Cys Glu Leu Thr Xaa Xaa Lys Asn Ala Ala Gin Gin 35 40 45

Xaa Val Leu Ser Ala Asp Asn Met Arg Glu Tyr Leu Ala Ala Gly Ala 50 55 60

Lys Glu Arg Gin Arg Leu Ala Thr Ser Leu Arg Asn Ala Ala Lys Xaa 65 70 75 80

Tyr Gly Glu Val Asp Glu Glu Ala Ala Thr Ala Leu Asp Asn Asp Gly 85 90 95

Glu Gly Thr Val Gin Ala Glu Ser Ala Gly Ala Val Gly Gly Asp Ser 100 105 110

Ser Ala Glu Leu Thr Asp Thr Pro Arg Val Ala Thr Ala Gly Glu Pro 115 120 125

Asn Phe Met Asp Leu Lys Glu Ala Ala Arg Lys Leu Glu Thr Gly Asp 130 135 140

Gin Gly Ala Ser Leu Ala His Xaa Gly Asp Gly Trp Asn Thr Xaa Thr 145 150 155 160

Leu Thr Leu Gin Gly Asp 165

(2) INFORMATION FOR SEQ ID NO: 91:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 5 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 91:

Arg Ala Glu Arg Met 1 5 (2) INFORMATION FOR SEQ ID NO: 92:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 263 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 92:

Val Ala Trp Met Ser Val Thr Ala Gly Gin Ala Glu Leu Thr Ala Ala 1 5 10 15

Gin Val Arg Val Ala Ala Ala Ala Tyr Glu Thr Ala Tyr Gly Leu Thr 20 25 30

Val Pro Pro Pro Val He Ala Glu Asn Arg Ala Glu Leu Met He Leu 35 40 45

He Ala Thr Asn Leu Leu Gly Gin Asn Thr Pro Ala He Ala Val Asn 50 55 60

Glu Ala Glu Tyr Gly Glu Met Trp Ala Gin Asp Ala Ala Ala Met Phe 65 70 75 80

Gly Tyr Ala Ala Ala Thr Ala Thr Ala Thr Ala Thr Leu Leu Pro Phe 85 90 95

Glu Glu Ala Pro Glu Met Thr Ser Ala Gly Gly Leu Leu Glu Gin Ala 100 105 110

Ala Ala Val Glu Glu Ala Ser Asp Thr Ala Ala Ala Asn Gin Leu Met 115 120 125

Asn Asn Val Pro Gin Ala Leu Lys Gin Leu Ala Gin Pro Thr Gin Gly 130 135 140

Thr Thr Pro Ser Ser Lys Leu Gly Gly Leu Trp Lys Thr Val Ser Pro 145 150 155 160

His Arg Ser Pro He Ser Asn Met Val Ser Met Ala Asn Asn His Met 165 170 175

Ser Met Thr Asn Ser Gly Val Ser Met Thr Asn Thr Leu Ser Ser Met 180 185 190

Leu Lys Gly Phe Ala Pro Ala Ala Ala Ala Gin Ala Val Gin Thr Ala 195 200 205

Ala Gin Asn Gly Val Arg Ala Met Ser Ser Leu Gly Ser Ser Leu Gly 210 215 220

Ser Ser Gly Leu Gly Gly Gly Val Ala Ala Asn Leu Gly Arg Ala Ala 225 230 235 240

Ser Val Arg Tyr Gly His Arg Asp Gly Gly Lys Tyr Ala Xaa Ser Gly 245 250 255

Arg Arg Asn Gly Gly Pro Ala 260

(2) INFORMATION FOR SEQ ID NO: 93:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 303 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 93:

Met Thr Tyr Ser Pro Gly Asn Pro Gly Tyr Pro Gin Ala Gin Pro Ala 1 5 10 15

Gly Ser Tyr Gly Gly Val Thr Pro Ser Phe Ala His Ala Asp Glu Gly 20 25 30

Ala Ser Lys Leu Pro Met Tyr Leu Asn He Ala Val Ala Val Leu Gly 35 40 45

Leu Ala Ala Tyr Phe Ala Ser Phe Gly Pro Met Phe Thr Leu Ser Thr 50 55 60

Glu Leu Gly Gly Gly Asp Gly Ala Val Ser Gly Asp Thr Gly Leu Pro 65 70 75 80

Val Gly Val Ala Leu Leu Ala Ala Leu Leu Ala Gly Val Val Leu Val 85 90 95

Pro Lys Ala Lys Ser His Val Thr Val Val Ala Val Leu Gly Val Leu 100 105 110

Gly Val Phe Leu Met Val Ser Ala Thr Phe Asn Lys Pro Ser Ala Tyr 115 120 125

Ser Thr Gly Trp Ala Leu Trp Val Val Leu Ala Phe He Val Phe Gin 130 135 140

Ala Val Ala Ala Val Leu Ala Leu Leu Val Glu Thr Gly Ala He Thr 145 150 155 160 Ala Pro Ala Pro Arg Pro Lys Phe Asp Pro Tyr Gly Gin Tyr Gly Arg 165 170 175

Tyr Gly Gin Tyr Gly Gin Tyr Gly Val Gin Pro Gly Gly Tyr Tyr Gly 180 185 190

Gin Gin Gly Ala Gin Gin Ala Ala Gly Leu Gin Ser Pro Gly Pro Gin 195 200 205

Gin Ser Pro Gin Pro Pro Gly Tyr Gly Ser Gin Tyr Gly Gly Tyr Ser 210 215 220

Ser Ser Pro Ser Gin Ser Gly Ser Gly Tyr Thr Ala Gin Pro Pro Ala 225 230 235 240

Gin Pro Pro Ala Gin Ser Gly Ser Gin Gin Ser His Gin Gly Pro Ser 245 250 255

Thr Pro Pro Thr Gly Phe Pro Ser Phe Ser Pro Pro Pro Pro Val Ser 260 265 270

Ala Gly Thr Gly Ser Gin Ala Gly Ser Ala Pro Val Asn Tyr Ser Asn 275 280 285

Pro Ser Gly Gly Glu Gin Ser Ser Ser Pro Gly Gly Ala Pro Val 290 295 300

(2) INFORMATION FOR SEQ ID NO: 94:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 507 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 94 :

ATGAAGATGG TGAAATCGAT CGCCGCAGGT CTGACCGCCG CGGCTGCAAT CGGCGCCGCT 60

GCGGCCGGTG TGACTTCGAT CATGGCTGGC GGCCCGGTCG TATACCAGAT GCAGCCGGTC 120

GTCTTCGGCG CGCCACTGCC GTTGGACCCG GCATCCGCCC CTGACGTCCC GACCGCCGCC 180

CAGTTGACCA GCCTGCTCAA CAGCCTCGCC GATCCCAACG TGTCGTTTGC GAACAAGGGC 240

AGTCTGGTCG AGGGCGGCAT CGGGGGCACC GAGGCGCGCA TCGCCGACCA CAAGCTGAAG 300

AAGGCCGCCG AGCACGGGGA TCTGCCGCTG TCGTTCAGCG TGACGAACAT CCAGCCGGCG 360

GCCGCCGGTT CGGCCACCGC CGACGTTTCC GTCTCGGGTC CGAAGCTCTC GTCGCCGGTC 420 ACGCAGAACG TCACGTTCGT GAATCAAGGC GGCTGGATGC TGTCACGCGC ATCGGCGATG 480 GAGTTGCTGC AGGCCGCAGG GAACTGA 507

(2) INFORMATION FOR SEQ ID NO: 95:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 168 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 95:

Met Lys Met Val Lys Ser He Ala Ala Gly Leu Thr Ala Ala Ala Ala 1 5 10 15

He Gly Ala Ala Ala Ala Gly Val Thr Ser He Met Ala Gly Gly Pro 20 25 30

Val Val Tyr Gin Met Gin Pro Val Val Phe Gly Ala Pro Leu Pro Leu 35 40 45

Asp Pro Ala Ser Ala Pro Asp Val Pro Thr Ala Ala Gin Leu Thr Ser 50 55 60

Leu Leu Asn Ser Leu Ala Asp Pro Asn Val Ser Phe Ala Asn Lys Gly 65 70 75 80

Ser Leu Val Glu Gly Gly He Gly Gly Thr Glu Ala Arg He Ala Asp 85 90 95

His Lys Leu Lys Lys Ala Ala Glu His Gly Asp Leu Pro Leu Ser Phe 100 105 110

Ser Val Thr Asn He Gin Pro Ala Ala Ala Gly Ser Ala Thr Ala Asp 115 120 125

Val Ser Val Ser Gly Pro Lys Leu Ser Ser Pro Val Thr Gin Asn Val 130 135 140

Thr Phe Val Asn Gin Gly Gly Trp Met Leu Ser Arg Ala Ser Ala Met 145 150 155 160

Glu Leu Leu Gin Ala Ala Gly Asn 165

(2) INFORMATION FOR SEQ ID NO: 96:

(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 500 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 96:

CGTGGCAATG TCGTTGACCG TCGGGGCCGG GGTCGCCTCC GCAGATCCCG TGGACGCGGT 60

CATTAACACC ACCTGCAATT ACGGGCAGGT AGTAGCTGCG CTCAACGCGA CGGATCCGGG 120

GGCTGCCGCA CAGTTCAACG CCTCACCGGT GGCGCAGTCC TATTTGCGCA ATTTCCTCGC 180

CGCACCGCCA CCTCAGCGCG CTGCCATGGC CGCGCAATTG CAAGCTGTGC CGGGGGCGGC 240

ACAGTACATC GGCCTTGTCG AGTCGGTTGC CGGCTCCTGC AACAACTATT AAGCCCATGC 300

GGGCCCCATC CCGCGACCCG GCATCGTCGC CGGGGCTAGG CCAGATTGCC CCGCTCCTCA 360

ACGGGCCGCA TCCCGCGACC CGGCATCGTC GCCGGGGCTA GGCCAGATTG CCCCGCTCCT 420

CAACGGGCCG CATCTCGTGC CGAATTCCTG CAGCCCGGGG GATCCACTAG TTCTAGAGCG 480

GCCGCCACCG CGGTGGAGCT 500 (2) INFORMATION FOR SEQ ID NO: 97:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 96 amino acids

(B) TYPE:, amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 97:

Val Ala Met Ser Leu Thr Val Gly Ala Gly Val Ala Ser Ala Asp Pro 1 5 10 15

Val Asp Ala Val He Asn Thr Thr Cys Asn Tyr Gly Gin Val Val Ala 20 25 30

Ala Leu Asn Ala Thr Asp Pro Gly Ala Ala Ala Gin Phe Asn Ala Ser 35 40 45

Pro Val Ala Gin Ser Tyr Leu Arg Asn Phe Leu Ala Ala Pro Pro Pro 50 55 60 Gin Arg Ala Ala Met Ala Ala Gin Leu Gin Ala Val Pro Gly Ala Ala 65 70 75 80

Gin Tyr He Gly Leu Val Glu Ser Val Ala Gly Ser Cys Asn Asn Tyr 85 90 95

(2) INFORMATION FOR SEQ ID NO: 98:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 154 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 98: ATGACAGAGC AGCAGTGGAA TTTCGCGGGT ATCGAGGCCG CGGCAAGCGC AATCCAGGGA 60 AATGTCACGT CCATTCATTC CCTCCTTGAC GAGGGGAAGC AGTCCCTGAC CAAGCTCGCA 120 GCGGCCTGGG GCGGTAGCGG TTCGGAAGCG TACC 154

(2) INFORMATION FOR SEQ ID NO: 99:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 51 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 99:

Met Thr Glu Gin Gin Trp Asn Phe Ala Gly He Glu Ala Ala Ala Ser 1 5 10 15

Ala He Gin Gly Asn Val Thr Ser He His Ser Leu Leu Asp Glu Gly 20 25 30

Lys Gin Ser Leu Thr Lys Leu Ala Ala Ala Trp Gly Gly Ser Gly Ser 35 40 45

Glu Ala Tyr 50

(2) INFORMATION FOR SEQ ID NO: 100:

(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 282 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 100:

CGGTCGCGCA CTTCCAGGTG ACTATGAAAG TCGGCTTCCG NCTGGAGGAT TCCTGAACCT 60

TCAAGCGCGG CCGATAACTG AGGTGCATCA TTAAGCGACT TTTCCAGAAC ATCCTGACGC 120

GCTCGAAACG CGGCACAGCC GACGGTGGCT CCGNCGAGGC GCTGNCTCCA AAATCCCTGA 180

GACAATTCGN CGGGGGCGCC TACAAGGAAG TCGGTGCTGA ATTCGNCGNG TATCTGGTCG 240 ACCTGTGTGG TCTGNAGCCG GACGAAGCGG TGCTCGACGT CG 282

(2) INFORMATION FOR SEQ ID NO: 101:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 3058 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 101:

GATCGTACCC GTGCGAGTGC TCGGGCCGTT TGAGGATGGA GTGCACGTGT CTTTCGTGAT 60

GGCATACCCA GAGATGTTGG CGGCGGCGGC TGACACCCTG CAGAGCATCG GTGCTACCAC 120

TGTGGCTAGC AATGCCGCTG CGGCGGCCCC GACGACTGGG GTGGTGCCCC CCGCTGCCGA 180

TGAGGTGTCG GCGCTGACTG CGGCGCACTT CGCCGCACAT GCGGCGATGT ATCAGTCCGT 240

GAGCGCTCGG GCTGCTGCGA TTCATGACCA GTTCGTGGCC ACCCTTGCCA GCAGCGCCAG 300

CTCGTATGCG GCCACTGAAG TCGCCAATGC GGCGGCGGCC AGCTAAGCCA GGAACAGTCG 360

GCACGAGAAA CCACGAGAAA TAGGGACACG TAATGGTGGA TTTCGGGGCG TTACCACCGG 420

AGATCAACTC CGCGAGGATG TACGCCGGCC CGGGTTCGGC CTCGCTGGTG GCCGCGGCTC 480

AGATGTGGGA CAGCGTGGCG AGTGACCTGT TTTCGGCCGC GTCGGCGTTT CAGTCGGTGG 540

TCTGGGGTCT GACGGTGGGG TCGTGGATAG GTTCGTCGGC GGGTCTGATG GTGGCGGCGG 600 CCTCGCCGTA TGTGGCGTGG ATGAGCGTCA CCGCGGGGCA GGCCGAGCTG ACCGCCGCCC 660

AGGTCCGGGT TGCTGCGGCG GCCTACGAGA CGGCGTATGG GCTGACGGTG CCCCCGCCGG 720

TGATCGCCGA GAACCGTGCT GAACTGATGA TTCTGATAGC GACCAACCTC TTGGGGCAAA 780

ACACCCCGGC GATCGCGGTC AACGAGGCCG AATACGGCGA GATGTGGGCC CAAGACGCCG 840

CCGCGATGTT TGGCTACGCC GCGGCGACGG CGACGGCGAC GGCGACGTTG CTGCCGTTCG 900

AGGAGGCGCC GGAGATGACC AGCGCGGGTG GGCTCCTCGA GCAGGCCGCC GCGGTCGAGG 960

AGGCCTCCGA CACCGCCGCG GCGAACCAGT TGATGAACAA TGTGCCCCAG GCGCTGCAAC 1020

AGCTGGCCCA GCCCACGCAG GGCACCACGC CTTCTTCCAA GCTGGGTGGC CTGTGGAAGA 1080

CGGTCTCGCC GCATCGGTCG CCGATCAGCA ACATGGTGTC GATGGCCAAC AACCACATGT 1140

CGATGACCAA CTCGGGTGTG TCGATGACCA ACACCTTGAG CTCGATGTTG AAGGGCTTTG 1200

CTCCGGCGGC GGCCGCCCAG GCCGTGCAAA CCGCGGCGCA AAACGGGGTC CGGGCGATGA 1260

GCTCGCTGGG CAGCTCGCTG GGTTCTTCGG GTCTGGGCGG TGGGGTGGCC GCCAACTTGG 1320

GTCGGGCGGC CTCGGTCGGT TCGTTGTCGG TGCCGCAGGC CTGGGCCGCG GCCAACCAGG 1380

CAGTCACCCC GGCGGCGCGG GCGCTGCCGC TGACCAGCCT GACCAGCGCC GCGGAAAGAG 1440

GGCCCGGGCA GATGCTGGGC GGGCTGCCGG TGGGGCAGAT GGGCGCCAGG GCCGGTGGTG 1500

GGCTCAGTGG TGTGCTGCGT GTTCCGCCGC GACCCTATGT GATGCCGCAT TCTCCGGCGG 1560

CCGGCTAGGA GAGGGGGCGC AGACTGTCGT TATTTGACCA GTGATCGGCG GTCTCGGTGT 1620

TTCCGCGGCC GGCTATGACA ACAGTCAATG TGCATGACAA GTTACAGGTA TTAGGTCCAG 1680

GTTCAACAAG GAGACAGGCA ACATGGCCTC ACGTTTTATG ACGGATCCGC ACGCGATGCG 1740

GGACATGGCG GGCCGTTTTG AGGTGCACGC CCAGACGGTG GAGGACGAGG CTCGCCGGAT 1800

GTGGGCGTCC GCGCAAAACA TTTCCGGTGC GGGCTGGAGT GGCATGGCCG AGGCGACCTC 1860

GCTAGACACC ATGGCCCAGA TGAATCAGGC GTTTCGCAAC ATCGTGAACA TGCTGCACGG 1920

GGTGCGTGAC GGGCTGGTTC GCGACGCCAA CAACTACGAG CAGCAAGAGC AGGCCTCCCA 1980

GCAGATCCTC AGCAGCTAAC GTCAGCCGCT GCAGCACAAT ACTTTTACAA GCGAAGGAGA 2040

ACAGGTTCGA TGACCATCAA CTATCAATTC GGGGATGTCG ACGCTCACGG CGCCATGATC 2100

CGCGCTCAGG CCGGGTTGCT GGAGGCCGAG CATCAGGCCA TCATTCGTGA TGTGTTGACC 2160

GCGAGTGACT TTTGGGGCGG CGCCGGTTCG GCGGCCTGCC AGGGGTTCAT TACCCAGTTG 2220

GGCCGTAACT TCCAGGTGAT CTACGAGCAG GCCAACGCCC ACGGGCAGAA GGTGCAGGCT 2280 GCCGGCAACA ACATGGCGCA AACCGACAGC GCCGTCGGCT CCAGCTGGGC CTGACACCAG 2340

GCCAAGGCCA GGGACGTGGT GTACGAGTGA AGTTCCTCGC GTGATCCTTC GGGTGGCAGT 2400

CTAAGTGGTC AGTGCTGGGG TGTTGGTGGT TTGCTGCTTG GCGGGTTCTT CGGTGCTGGT 2460

CAGTGCTGCT CGGGCTCGGG TGAGGACCTC GAGGCCCAGG TAGCGCCGTC CTTCGATCCA 2520

TTCGTCGTGT TGTTCGGCGA GGACGGCTCC GACGAGGCGG ATGATCGAGG CGCGGTCGGG 2580

GAAGATGCCC ACGACGTCGG TTCGGCGTCG TACCTCTCGG TTGAGGCGTT CCTGGGGGTT 2640

GTTGGACCAG ATTTGGCGCC AGATCTGCTT GGGGAAGGCG GTGAACGCCA GCAGGTCGGT 2700

GCGGGCGGTG TCGAGGTGCT CGGCCACCGC GGGGAGTTTG TCGGTCAGAG CGTCGAGTAC 2760

CCGATCATAT TGGGCAACAA CTGATTCGGC GTCGGGCTGG TCGTAGATGG AGTGCAGCAG 2820

GGTGCGCACC CACGGCCAGG AGGGCTTCGG GGTGGCTGCC ATCAGATTGG CTGCGTAGTG 2880

GGTTCTGCAG CGCTGCCAGG CCGCTGCGGG CAGGGTGGCG CCGATCGCGG CCACCAGGCC 2940

GGCGTGGGCG TCGCTGGTGA CCAGCGCGAC CCCGGACAGG CCGCGGGCGA CCAGGTCGCG 3000

GAAGAACGCC AGCCAGCCGG CCCCGTCCTC GGCGGAGGTG ACCTGGATGC CCAGGATC 3058 (2) INFORMATION FOR SEQ ID NO: 102:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 391 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 102:

Met Val Asp Phe Gly Ala Leu Pro Pro Glu He Asn Ser Ala Arg Met 1 5 10 15

Tyr Ala Gly Pro Gly Ser Ala Ser Leu Val Ala Ala Ala Gin Met Trp 20 25 30

Asp Ser Val Ala Ser Asp Leu Phe Ser Ala Ala Ser Ala Phe Gin Ser 35 40 45

Val Val Trp Gly Leu Thr Val Gly Ser Trp He Gly Ser Ser Ala Gly 50 55 60

Leu Met Val Ala Ala Ala Ser Pro Tyr Val Ala Trp Met Ser Val Thr 65 70 75 80 Ala Gly Gin Ala Glu Leu Thr Ala Ala Gin Val Arg Val Ala Ala Ala 85 90 95

Ala Tyr Glu Thr Ala Tyr Gly Leu Thr Val Pro Pro Pro Val He Ala 100 105 110

Glu Asn Arg Ala Glu Leu Met He Leu He Ala Thr Asn Leu Leu Gly 115 120 125

Gin Asn Thr Pro Ala He Ala Val Asn Glu Ala Glu Tyr Gly Glu Met 130 135 140

Trp Ala Gin Asp Ala Ala Ala Met Phe Gly Tyr Ala Ala Ala Thr Ala 145 150 155 160

Thr Ala Thr Ala Thr Leu Leu Pro Phe Glu Glu Ala Pro Glu Met Thr 165 170 175

Ser Ala Gly Gly Leu Leu Glu Gin Ala Ala Ala Val Glu Glu Ala Ser 180 185 190

Asp Thr Ala Ala Ala Asn Gin Leu Met Asn Asn Val Pro Gin Ala Leu 195 200 205

Gin Gin Leu Ala Gin Pro Thr Gin Gly Thr Thr Pro Ser Ser Lys Leu 210 215 220

Gly Gly Leu Trp Lys Thr Val Ser Pro His Arg Ser Pro He Ser Asn 225 230 235 240

Met Val Ser Met Ala Asn Asn His Met Ser Met Thr Asn Ser Gly Val 245 250 255

Ser Met Thr Asn Thr Leu Ser Ser Met Leu Lys Gly Phe Ala Pro Ala 260 265 270

Ala Ala Ala Gin Ala Val Gin Thr Ala Ala Gin Asn Gly Val Arg Ala 275 280 285

Met Ser Ser Leu Gly Ser Ser Leu Gly Ser Ser Gly Leu Gly Gly Gly 290 295 300

Val Ala Ala Asn Leu Gly Arg Ala Ala Ser Val Gly Ser Leu Ser Val 305 310 315 320

Pro Gin Ala Trp Ala Ala Ala Asn Gin Ala Val Thr Pro Ala Ala Arg 325 330 335

Ala Leu Pro Leu Thr Ser Leu Thr Ser Ala Ala Glu Arg Gly Pro Gly 340 345 350

Gin Met Leu Gly Gly Leu Pro Val Gly Gin Met Gly Ala Arg Ala Gly 355 360 365 Gly Gly Leu Ser Gly Val Leu Arg Val Pro Pro Arg Pro Tyr Val Met 370 375 380

Pro His Ser Pro Ala Ala Gly 385 390

(2) INFORMATION FOR SEQ ID NO: 103:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1725 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 103:

GACGTCAGCA CCCGCCGTGC AGGGCTGGAG CGTGGTCGGT TTTGATCTGC GGTCAAGGTG 60

ACGTCCCTCG GCGTGTCGCC GGCGTGGATG CAGACTCGAT GCCGCTCTTT AGTGCAACTA 120

ATTTCGTTGA AGTGCCTGCG AGGTATAGGA CTTCACGATT GGTTAATGTA GCGTTCACCC 180

CGTGTTGGGG TCGATTTGGC CGGACCAGTC GTCACCAACG CTTGGCGTGC GCGCCAGGCG 240

GGCGATCAGA TCGCTTGACT ACCAATCAAT CTTGAGCTCC CGGGCCGATG CTCGGGCTAA 300

ATGAGGAGGA GCACGCGTGT CTTTCACTGC GCAACCGGAG ATGTTGGCGG CCGCGGCTGG 360

CGAACTTCGT TCCCTGGGGG CAACGCTGAA GGCTAGCAAT GCCGCCGCAG CCGTGCCGAC 420

GACTGGGGTG GTGCCCCCGG CTGCCGACGA GGTGTCGCTG CTGCTTGCCA CACAATTCCG 480

TACGCATGCG GCGACGTATC AGACGGCCAG CGCCAAGGCC GCGGTGATCC ATGAGCAGTT 540

TGTGACCACG CTGGCCACCA GCGCTAGTTC ATATGCGGAC ACCGAGGCCG CCAACGCTGT 600

GGTCACCGGC TAGCTGACCT GACGGTATTC GAGCGGAAGG ATTATCGAAG TGGTGGATTT 660

CGGGGCGTTA CCACCGGAGA TCAACTCCGC GAGGATGTAC GCCGGCCCGG GTTCGGCCTC 720

GCTGGTGGCC GCCGCGAAGA TGTGGGACAG CGTGGCGAGT GACCTGTTTT CGGCCGCGTC 780

GGCGTTTCAG TCGGTGGTCT GGGGTCTGAC GGTGGGGTCG TGGATAGGTT CGTCGGCGGG 840

TCTGATGGCG GCGGCGGCCT CGCCGTATGT GGCGTGGATG AGCGTCACCG CGGGGCAGGC 900

CCAGCTGACC GCCGCCCAGG TCCGGGTTGC TGCGGCGGCC TACGAGACAG CGTATAGGCT 960

GACGGTGCCC CCGCCGGTGA TCGCCGAGAA CCGTACCGAA CTGATGACGC TGACCGCGAC 1020

CAACCTCTTG GGGCAAAACA CGCCGGCGAT CGAGGCCAAT CAGGCCGCAT ACAGCCAGAT 1080 GTGGGGCCAA GACGCGGAGG CGATGTATGG CTACGCCGCC ACGGCGGCGA CGGCGACCGA 1140

GCCGTTGCTG CCGTTCGAGG ACGCCCCACT GATCACCAAC CCCGGCGGGC TCCTTGAGCA 1200

GGCCGTCGCG GTCGAGGAGG CCATCGACAC CGCCGCGGCG AACCAGTTGA TGAACAATGT 1260

GCCCCAAGCG CTGCAACAGC TGGCCCAGCC AGCGCAGGGC GTCGTACCTT CTTCCAAGCT 1320

GGGTGGGCTG TGGACGGCGG TCTCGCCGCA TCTGTCGCCG CTCAGCAACG TCAGTTCGAT 1380

AGCCAACAAC CACATGTCGA TGATGGGCAC GGGTGTGTCG ATGACCAACA CCTTGCACTC 1440

GATGTTGAAG GGCTTAGCTC CGGCGGCGGC TCAGGCCGTG GAAACCGCGG CGGAAAACGG 1500

GGTCTGGGCG ATGAGCTCGC TGGGCAGCCA GCTGGGTTCG TCGCTGGGTT CTTCGGGTCT 1560

GGGCGCTGGG GTGGCCGCCA ACTTGGGTCG GGCGGCCTCG GTCGGTTCGT TGTCGGTGCC 1620

GCCAGCATGG GCCGCGGCCA ACCAGGCGGT CACCCCGGCG GCGCGGGCGC TGCCGCTGAC 1680

CAGCCTGACC AGCGCCGCCC AAACCGCCCC CGGACACATG CTGGG 1725 (2) INFORMATION FOR SEQ ID NO: 104:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 359 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 104:

Val Val Asp Phe Gly Ala Leu Pro Pro Glu He Asn Ser Ala Arg Met 1 5 10 15

Tyr Ala Gly Pro Gly Ser Ala Ser Leu Val Ala Ala Ala Lys Met Trp 20 25 30

Asp Ser Val Ala Ser Asp Leu Phe Ser Ala Ala Ser Ala Phe Gin Ser 35 40 45

Val Val Trp Gly Leu Thr Val Gly Ser Trp He Gly Ser Ser Ala Gly 50 55 60

Leu Met Ala Ala Ala Ala Ser Pro Tyr Val Ala Trp Met Ser Val Thr 65 70 75 80

Ala Gly Gin Ala Gin Leu Thr Ala Ala Gin Val Arg Val Ala Ala Ala 85 90 95 Ala Tyr Glu Thr Ala Tyr Arg Leu Thr Val Pro Pro Pro Val He Ala 100 105 110

Glu Asn Arg Thr Glu Leu Met Thr Leu Thr Ala Thr Asn Leu Leu Gly 115 120 125

Gin Asn Thr Pro Ala He Glu Ala Asn Gin Ala Ala Tyr Ser Gin Met 130 135 140

Trp Gly Gin Asp Ala Glu Ala Met Tyr Gly Tyr Ala Ala Thr Ala Ala 145 150 155 160

Thr Ala Thr Glu Ala Leu Leu Pro Phe Glu Asp Ala Pro Leu He Thr 165 170 175

Asn Pro Gly Gly Leu Leu Glu Gin Ala Val Ala Val Glu Glu Ala He 180 185 190

Asp Thr Ala Ala Ala Asn Gin Leu Met Asn Asn Val Pro Gin Ala Leu 195 200 205

Gin Gin Leu Ala Gin Pro Ala Gin Gly Val Val Pro Ser Ser Lys Leu 210 215 220

Gly Gly Leu Trp Thr Ala Val Ser Pro His Leu Ser Pro Leu Ser Asn 225 230 235 240

Val Ser Ser He Ala Asn Asn His Met Ser Met Met Gly Thr Gly Val 245 250 255

Ser Met Thr Asn Thr Leu His Ser Met Leu Lys Gly Leu Ala Pro Ala 260 265 270

Ala Ala Gin Ala Val Glu Thr Ala Ala Glu Asn Gly Val Trp Ala Met 275 280 285

Ser Ser Leu Gly Ser Gin Leu Gly Ser Ser Leu Gly Ser Ser Gly Leu 290 295 300

Gly Ala Gly Val Ala Ala Asn Leu Gly Arg Ala Ala Ser Val Gly Ser 305 310 315 320

Leu Ser Val Pro Pro Ala Trp Ala Ala Ala Asn Gin Ala Val Thr Pro 325 330 335

Ala Ala Arg Ala Leu Pro Leu Thr Ser Leu Thr Ser Ala Ala Gin Thr 340 345 350

Ala Pro Gly His Met Leu Gly 355

(2) INFORMATION FOR SEQ ID NO: 105:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 3027 base pairs (B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 105:

AGTTCAGTCG AGAATGATAC TGACGGGCTG TATCCACGAT GGCTGAGACA ACCGAACCAC 60

CGTCGGACGC GGGGACATCG CAAGCCGACG CGATGGCGTT GGCCGCCGAA GCCGAAGCCG 120

CCGAAGCCGA AGCGCTGGCC GCCGCGGCGC GGGCCCGTGC CCGTGCCGCC CGGTTGAAGC 180

GTGAGGCGCT GGCGATGGCC CCAGCCGAGG ACGAGAACGT CCCCGAGGAT ATGCAGACTG 240

GGAAGACGCC GAAGACTATG ACGACTATGA CGACTATGAG GCCGCAGACC AGGAGGCCGC 300

ACGGTCGGCA TCCTGGCGAC GGCGGTTGCG GGTGCGGTTA CCAAGACTGT CCACGATTGC 360

CATGGCGGCC GCAGTCGTCA TCATCTGCGG CTTCACCGGG CTCAGCGGAT ACATTGTGTG 420

GCAACACCAT GAGGCCACCG AACGCCAGCA GCGCGCCGCG GCGTTCGCCG CCGGAGCCAA 480

GCAAGGTGTC ATCAACATGA CCTCGCTGGA CTTCAACAAG GCCAAAGAAG ACGTCGCGCG 540

TGTGATCGAC AGCTCCACCG GCGAATTCAG GGATGACTTC CAGCAGCGGG CAGCCGATTT 600

CACCAAGGTT GTCGAACAGT CCAAAGTGGT CACCGAAGGC ACGGTGAACG CGACAGCCGT 660

CGAATCCATG AACGAGCATT CCGCCGTGGT GCTCGTCGCG GCGACTTCAC GGGTCACCAA 720

TTCCGCTGGG GCGAAAGACG AACCACGTGC GTGGCGGCTC AAAGTGACCG TGACCGAAGA 780

GGGGGGACAG TACAAGATGT CGAAAGTTGA GTTCGTACCG TGACCGATGA CGTACGCGAC 840

GTCAACACCG AAACCACTGA CGCCACCGAA GTCGCTGAGA TCGACTCAGC CGCAGGCGAA 900

GCCGGTGATT CGGCGACCGA GGCATTTGAC ACCGACTCTG CAACGGAATC TACCGCGCAG 960

AAGGGTCAGC GGCACCGTGA CCTGTGGCGA ATGCAGGTTA CCTTGAAACC CGTTCCGGTG 1020

ATTCTCATCC TGCTCATGTT GATCTCTGGG GGCGCGACGG GATGGCTATA CCTTGAGCAA 1080

TACGACCCGA TCAGCAGACG GACTCCGGCG CCGCCCGTGC TGCCGTCGCC GCGGCGTCTG 1140

ACGGGACAAT CGCGCTGTTG TGTATTCACC CGACACGTCG ACCAAGACTT CGCTACCGCC 1200

AGGTCGCACC TCGCCGGCGA TTTCCTGTCC TATACGACCA GTTCACGCAG CAGATCGTGG 1260

CTCCGGCGGC CAAACAGAAG TCACTGAAAA CCACCGCCAA GGTGGTGCGC GCGGCCGTGT 1320

CGGAGCTACA TCCGGATTCG GCCGTCGTTC TGGTTTTTGT CGACCAGAGC ACTACCAGTA 1380 AGGACAGCCC CAATCCGTCG ATGGCGGCCA GCAGCGTGAT GGTGACCCTA GCCAAGGTCG 1440

ACGGCAATTG GCTGATCACC AAGTTCACCC CGGTTTAGGT TGCCGTAGGC GGTCGCCAAG 1500

TCTGACGGGG GCGCGGGTGG CTGCTCGTGC GAGATACCGG CCGTTCTCCG GACAATCACG 1560

GCCCGACCTC AAACAGATCT CGGCCGCTGT CTAATCGGCC GGGTTATTTA AGATTAGTTG 1620

CCACTGTATT TACCTGATGT TCAGATTGTT CAGCTGGATT TAGCTTCGCG GCAGGGCGGC 1680

TGGTGCACTT TGCATCTGGG GTTGTGACTA CTTGAGAGAA TTTGACCTGT TGCCGACGTT 1740

GTTTGCTGTC CATCATTGGT GCTAGTTATG GCCGAGCGGA AGGATTATCG AAGTGGTGGA 1800

CTTCGGGGCG TTACCACCGG AGATCAACTC CGCGAGGATG TACGCCGGCC CGGGTTCGGC 1860

CTCGCTGGTG GCCGCCGCGA AGATGTGGGA CAGCGTGGCG AGTGACCTGT TTTCGGCCGC 1920

GTCGGCGTTT CAGTCGGTGG TCTGGGGTCT GACGACGGGA TCGTGGATAG GTTCGTCGGC 1980

GGGTCTGATG GTGGCGGCGG CCTCGCCGTA TGTGGCGTGG ATGAGCGTCA CCGCGGGGCA 2040

GGCCGAGCTG ACCGCCGCCC AGGTCCGGGT TGCTGCGGCG GCCTACGAGA CGGCGTATGG 2100

GCTGACGGTG CCCCCGCCGG TGATCGCCGA GAACCGTGCT GAACTGATGA TTCTGATAGC 2160

GACCAACCTC TTGGGGCAAA ACACCCCGGC GATCGCGGTC AACGAGGCCG AATACGGGGA 2220

GATGTGGGCC CAAGACGCCG CCGCGATGTT TGGCTACGCC GCCACGGCGG CGACGGCGAC 2280

CGAGGCGTTG CTGCCGTTCG AGGACGCCCC ACTGATCACC AACCCCGGCG GGCTCCTTGA 2340

GCAGGCCGTC GCGGTCGAGG AGGCCATCGA CACCGCCGCG GCGAACCAGT TGATGAACAA 2400

TGTGCCCCAA GCGCTGCAAC AACTGGCCCA GCCCACGAAA AGCATCTGGC CGTTCGACCA 2460

ACTGAGTGAA CTCTGGAAAG CCATCTCGCC GCATCTGTCG CCGCTCAGCA ACATCGTGTC 2520

GATGCTCAAC AACCACGTGT CGATGACCAA CTCGGGTGTG TCGATGGCCA GCACCTTGCA 2580

CTCAATGTTG AAGGGCTTTG CTCCGGCGGC GGCTCAGGCC GTGGAAACCG CGGCGCAAAA 2640

CGGGGTCCAG GCGATGAGCT CGCTGGGCAG CCAGCTGGGT TCGTCGCTGG GTTCTTCGGG 2700

TCTGGGCGCT GGGGTGGCCG CCAACTTGGG TCGGGCGGCC TCGGTCGGTT CGTTGTCGGT 2760

GCCGCAGGCC TGGGCCGCGG CCAACCAGGC GGTCACCCCG GCGGCGCGGG CGCTGCCGCT 2820

GACCAGCCTG ACCAGCGCCG CCCAAACCGC CCCCGGACAC ATGCTGGGCG GGCTACCGCT 2880

GGGGCAACTG ACCAATAGCG GCGGCGGGTT CGGCGGGGTT AGCAATGCGT TGCGGATGCC 2940

GCCGCGGGCG TACGTAATGC CCCGTGTGCC CGCCGCCGGG TAACGCCGAT CCGCACGCAA 3000 TGCGGGCCCT CTATGCGGGC AGCGATC 3027

(2) INFORMATION FOR SEQ ID NO: 106:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 396 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 106:

Val Val Asp Phe Gly Ala Leu Pro Pro Glu He Asn Ser Ala Arg Met 1 5 10 15

Tyr Ala Gly Pro Gly Ser Ala Ser Leu Val Ala Ala Ala Lys Met Trp 20 25 30

Asp Ser Val Ala Ser Asp Leu Phe Ser Ala Ala Ser Ala Phe Gin Ser 35 40 45

Val Val Trp Gly Leu Thr Thr Gly Ser Trp He Gly Ser Ser Ala Gly 50 55 60

Leu Met Val Ala Ala Ala Ser Pro Tyr Val Ala Trp Met Ser Val Thr 65 70 75 80

Ala Gly Gin Ala Glu Leu Thr Ala Ala Gin Val Arg Val Ala Ala Ala 85 90 95

Ala Tyr Glu Thr Ala Tyr Gly Leu Thr Val Pro Pro Pro Val He Ala 100 105 110

Glu Asn Arg Ala Glu Leu Met He Leu He Ala Thr Asn Leu Leu Gly 115 120 125

Gin Asn Thr Pro Ala He Ala Val Asn Glu Ala Glu Tyr Gly Glu Met 130 135 140

Trp Ala Gin Asp Ala Ala Ala Met Phe Gly Tyr Ala Ala Thr Ala Ala 145 150 155 160

Thr Ala Thr Glu Ala Leu Leu Pro Phe Glu Asp Ala Pro Leu He Thr 165 170 175

Asn Pro Gly Gly Leu Leu Glu Gin Ala Val Ala Val Glu Glu Ala He 180 185 190

Asp Thr Ala Ala Ala Asn Gin Leu Met Asn Asn Val Pro Gin Ala Leu 195 200 205 Gin Gin Leu Ala Gin Pro Thr Lys Ser He Trp Pro Phe Asp Gin Leu 210 215 220

Ser Glu Leu Trp Lys Ala He Ser Pro His Leu Ser Pro Leu Ser Asn 225 230 235 240

He Val Ser Met Leu Asn Asn His Val Ser Met Thr Asn Ser Gly Val 245 250 255

Ser Met Ala Ser Thr Leu His Ser Met Leu Lys Gly Phe Ala Pro Ala 260 265 270

Ala Ala Gin Ala Val Glu Thr Ala Ala Gin Asn Gly Val Gin Ala Met 275 280 285

Ser Ser Leu Gly Ser Gin Leu Gly Ser Ser Leu Gly Ser Ser Gly Leu 290 295 300

Gly Ala Gly Val Ala Ala Asn Leu Gly Arg Ala Ala Ser Val Gly Ser 305 310 315 320

Leu Ser Val Pro Gin Ala Trp Ala Ala Ala Asn Gin Ala Val Thr Pro 325 330 335

Ala Ala Arg Ala Leu Pro Leu Thr Ser Leu Thr Ser Ala Ala Gin Thr 340 345 350

Ala Pro Gly His Met Leu Gly Gly Leu Pro Leu Gly Gin Leu Thr Asn 355 360 365

Ser Gly Gly Gly Phe Gly Gly Val Ser Asn Ala Leu Arg Met Pro Pro 370 375 380

Arg Ala Tyr Val Met Pro Arg Val Pro Ala Ala Gly 385 390 395

(2) INFORMATION FOR SEQ ID NO: 107:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1616 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 107:

CATCGGAGGG AGTGATCACC ATGCTGTGGC ACGCAATGCC ACCGGAGTAA ATACCGCACG 60

GCTGATGGCC GGCGCGGGTC CGGCTCCAAT GCTTGCGGCG GCCGCGGGAT GGCAGACGCT 120

TTCGGCGGCT CTGGACGCTC AGGCCGTCGA GTTGACCGCG CGCCTGAACT CTCTGGGAGA 180 AGCCTGGACT GGAGGTGGCA GCGACAAGGC GCTTGCGGCT GCAACGCCGA TGGTGGTCTG 240

GCTACAAACC GCGTCAACAC AGGCCAAGAC CCGTGCGATG CAGGCGACGG CGCAAGCCGC 300

GGCATACACC CAGGCCATGG CCACGACGCC GTCGCTGCCG GAGATCGCCG CCAACCACAT 360

CACCCAGGCC GTCCTTACGG CCACCAACTT CTTCGGTATC AACACGATCC CGATCGCGTT 420

GACCGAGATG GATTATTTCA TCCGTATGTG GAACCAGGCA GCCCTGGCAA TGGAGGTCTA 480

CCAGGCCGAG ACCGCGGTTA ACACGCTTTT CGAGAAGCTC GAGCCGATGG CGTCGATCCT 540

TGATCCCGGC GCGAGCCAGA GCACGACGAA CCCGATCTTC GGAATGCCCT CCCCTGGCAG 600

CTCAACACCG GTTGGCCAGT TGCCGCCGGC GGCTACCCAG ACCCTCGGCC AACTGGGTGA 660

GATGAGCGGC CCGATGCAGC AGCTGACCCA GCCGCTGCAG CAGGTGACGT CGTTGTTCAG 720

CCAGGTGGGC GGCACCGGCG GCGGCAACCC AGCCGACGAG GAAGCCGCGC AGATGGGCCT 780

GCTCGGCACC AGTCCGCTGT CGAACCATCC GCTGGCTGGT GGATCAGGCC CCAGCGCGGG 840

CGCGGGCCTG CTGCGCGCGG AGTCGCTACC TGGCGCAGGT GGGTCGTTGA CCCGCACGCC 900

GCTGATGTCT CAGCTGATCG AAAAGCCGGT TGCCCCCTCG GTGATGCCGG CGGCTGCTGC 960

CGGATCGTCG GCGACGGGTG GCGCCGCTCC GGTGGGTGCG GGAGCGATGG GCCAGGGTGC 1020

GCAATCCGGC GGCTCCACCA GGCCGGGTCT GGTCGCGCCG GCACCGCTCG CGCAGGAGCG 1080

TGAAGAAGAC GACGAGGACG ACTGGGACGA AGAGGACGAC TGGTGAGCTC CCGTAATGAC 1140

AACAGACTTC CCGGCCACCC GGGCCGGAAG ACTTGCCAAC ATTTTGGCGA GGAAGGTAAA 1200

GAGAGAAAGT AGTCCAGCAT GGCAGAGATG AAGACCGATG CCGCTACCCT CGCGCAGGAG 1260

GCAGGTAATT TCGAGCGGAT CTCCGGCGAC CTGAAAACCC AGATCGACCA GGTGGAGTCG 1320

ACGGCAGGTT CGTTGCAGGG CCAGTGGCGC GGCGCGGCGG GGACGGCCGC CCAGGCCGCG 1380

GTGGTGCGCT TCCAAGAAGC AGCCAATAAG CAGAAGCAGG AACTCGACGA GATCTCGACG 1440

AATATTCGTC AGGCCGGCGT CCAATACTCG AGGGCCGACG AGGAGCAGCA GCAGGCGCTG 1500

TCCTCGCAAA TGGGCTTCTG ACCCGCTAAT ACGAAAAGAA ACGGAGCAAA AACATGACAG 1560

AGCAGCAGTG GAATTTCGCG GGTATCGAGG CCGCGGCAAG CGCAATCCAG GGAAAT 1616 (2) INFORMATION FOR SEQ ID NO: 108:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 432 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single (D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 108:

CTAGTGGATG GGACCATGGC CATTTTCTGC AGTCTCACTG CCTTCTGTGT TGACATTTTG 60

GCACGCCGGC GGAAACGAAG CACTGGGGTC GAAGAACGGC TGCGCTGCCA TATCGTCCGG 120

AGCTTCCATA CCTTCGTGCG GCCGGAAGAG CTTGTCGTAG TCGGCCGCCA TGACAACCTC 180

TCAGAGTGCG CTCAAACGTA TAAACACGAG AAAGGGCGAG ACCGACGGAA GGTCGAACTC 240

GCCCGATCCC GTGTTTCGCT ATTCTACGCG AACTCGGCGT TGCCCTATGC GAACATCCCA 300

GTGACGTTGC CTTCGGTCGA AGCCATTGCC TGACCGGCTT CGCTGATCGT CCGCGCCAGG 360

TTCTGCAGCG CGTTGTTCAG CTCGGTAGCC GTGGCGTCCC ATTTTTGCTG GACACCCTGG 420

TACGCCTCCG AA 432 (2) INFORMATION FOR SEQ ID NO: 109:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 368 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 109:

Met Leu Trp His Ala Met Pro Pro Glu Xaa Asn Thr Ala Arg Leu Met 1 5 10 15

Ala Gly Ala Gly Pro Ala Pro Met Leu Ala Ala Ala Ala Gly Trp Gin 20 25 30

Thr Leu Ser Ala Ala Leu Asp Ala Gin Ala Val Glu Leu Thr Ala Arg 35 40 45

Leu Asn Ser Leu Gly Glu Ala Trp Thr Gly Gly Gly Ser Asp Lys Ala 50 55 60

Leu Ala Ala Ala Thr Pro Met Val Val Trp Leu Gin Thr Ala Ser Thr 65 70 75 80

Gin Ala Lys Thr Arg Ala Met Gin Ala Thr Ala Gin Ala Ala Ala Tyr 85 90 95 Thr Gin Ala Met Ala Thr Thr Pro Ser Leu Pro Glu He Ala Ala Asn 100 105 110

His He Thr Gin Ala Val Leu Thr Ala Thr Asn Phe Phe Gly He Asn 115 120 125

Thr He Pro He Ala Leu Thr Glu Met Asp Tyr Phe He Arg Met Trp 130 135 140

Asn Gin Ala Ala Leu Ala Met Glu Val Tyr Gin Ala Glu Thr Ala Val 145 150 155 160

Asn Thr Leu Phe Glu Lys Leu Glu Pro Met Ala Ser He Leu Asp Pro 165 170 175

Gly Ala Ser Gin Ser Thr Thr Asn Pro He Phe Gly Met Pro Ser Pro 180 185 190

Gly Ser Ser Thr Pro Val Gly Gin Leu Pro Pro Ala Ala Thr Gin Thr 195 200 205

Leu Gly Gin Leu Gly Glu Met Ser Gly Pro Met Gin Gin Leu Thr Gin 210 215 220

Pro Leu Gin Gin Val Thr Ser Leu Phe Ser Gin Val Gly Gly Thr Gly 225 230 235 240

Gly Gly Asn Pro Ala Asp Glu Glu Ala Ala Gin Met Gly Leu Leu Gly 245 250 255

Thr Ser Pro Leu Ser Asn His Pro Leu Ala Gly Gly Ser Gly Pro Ser 260 265 270

Ala Gly Ala Gly Leu Leu Arg Ala Glu Ser Leu Pro Gly Ala Gly Gly 275 280 285

Ser Leu Thr Arg Thr Pro Leu Met Ser Gin Leu He Glu Lys Pro Val 290 295 300

Ala Pro Ser Val Met Pro Ala Ala Ala Ala Gly Ser Ser Ala Thr Gly 305 310 315 320

Gly Ala Ala Pro Val Gly Ala Gly Ala Met Gly Gin Gly Ala Gin Ser 325 330 335

Gly Gly Ser Thr Arg Pro Gly Leu Val Ala Pro Ala Pro Leu Ala Gin 340 345 350

Glu Arg Glu Glu Asp Asp Glu Asp Asp Trp Asp Glu Glu Asp Asp Trp 355 360 365

(2) INFORMATION FOR SEQ ID NO: 110: (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 100 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 110:

Met Ala Glu Met Lys Thr Asp Ala Ala Thr Leu Ala Gin Glu Ala Gly 1 5 10 15

Asn Phe Glu Arg He Ser Gly Asp Leu Lys Thr Gin He Asp Gin Val 20 25 30

Glu Ser Thr Ala Gly Ser Leu Gin Gly Gin Trp Arg Gly Ala Ala Gly 35 40 45

Thr Ala Ala Gin Ala Ala Val Val Arg Phe Gin Glu Ala Ala Asn Lys 50 55 60

Gin Lys Gin Glu Leu Asp Glu He Ser Thr Asn He Arg Gin Ala Gly 65 70 75 80

Val Gin Tyr Ser Arg Ala Asp Glu Glu Gin Gin Gin Ala Leu Ser Ser 85 90 95

Gin Met Gly Phe 100

(2) INFORMATION FOR SEQ ID NO: 111:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 396 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 111:

GATCTCCGGC GACCTGAAAA CCCAGATCGA CCAGGTGGAG TCGACGGCAG GTTCGTTGCA 60

GGGCCAGTGG CGCGGCGCGG CGGGGACGGC CGCCCAGGCC GCGGTGGTGC GCTTCCAAGA 120

AGCAGCCAAT AAGCAGAAGC AGGAACTCGA CGAGATCTCG ACGAATATTC GTCAGGCCGG 180

CGTCCAATAC TCGAGGGCCG ACGAGGAGCA GCAGCAGGCG CTGTCCTCGC AAATGGGCTT 240 CTGACCCGCT AATACGAAAA GAAACGGAGC AAAAACATGA CAGAGCAGCA GTGGAATTTC 300

GCGGGTATCG AGGCCGCGGC AAGCGCAATC CAGGGAAATG TCACGTCCAT TCATTCCCTC 360

CTTGACGAGG GGAAGCAGTC CCTGACCAAG CTCGCA 396 (2) INFORMATION FOR SEQ ID NO: 112:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 80 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 112:

He Ser Gly Asp Leu Lys Thr Gin He Asp Gin Val Glu Ser Thr Ala 1 5 10 15

Gly Ser Leu Gin Gly Gin Trp Arg Gly Ala Ala Gly Thr Ala Ala Gin 20 25 30

Ala Ala Val Val Arg Phe Gin Glu Ala Ala Asn Lys Gin Lys Gin Glu 35 40 45

Leu Asp Glu He Ser Thr Asn He Arg Gin Ala Gly Val Gin Tyr Ser 50 55 60

Arg Ala Asp Glu Glu Gin Gin Gin Ala Leu Ser Ser Gin Met Gly Phe 65 70 75 80

(2) INFORMATION FOR SEQ ID NO:113:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 387 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 113:

GTGGATCCCG ATCCCGTGTT TCGCTATTCT ACGCGAACTC GGCGTTGCCC TATGCGAACA 60

TCCCAGTGAC GTTGCCTTCG GTCGAAGCCA TTGCCTGACC GGCTTCGCTG ATCGTCCGCG 120

CCAGGTTCTG CAGCGCGTTG TTCAGCTCGG TAGCCGTGGC GTCCCATTTT TGCTGGACAC 180 CCTGGTACGC CTCCGAACCG CTACCGCCCC AGGCCGCTGC GAGCTTGGTC AGGGACTGCT 240

TCCCCTCGTC AAGGAGGGAA TGAATGGACG TGACATTTCC CTGGATTGCG CTTGCCGCGG 300

CCTCGATACC CGCGAAATTC CACTGCTGCT CTGTCATGTT TTTGCTCCGT TTCTTTTCGT 360

ATTAGCGGGT CAGAAGCCCA TTTGCGA 387 (2) INFORMATION FOR SEQ ID NO: 114:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 272 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 114:

CGGCACGAGG ATCTCGGTTG GCCCAACGGC GCTGGCGAGG GCTCCGTTCC GGGGGCGAGC 60

TGCGCGCCGG ATGCTTCCTC TGCCCGCAGC CGCGCCTGGA TGGATGGACC AGTTGCTACC 120

TTCCCGACGT TTCGTTCGGT GTCTGTGCGA TAGCGGTGAC CCCGGCGCGC ACGTCGGGAG 180

TGTTGGGGGG CAGGCCGGGT CGGTGGTTCG GCCGGGGACG CAGACGGTCT GGACGGAACG 240

GGCGGGGGTT CGCCGATTGG CATCTTTGCC CA 272 (2) INFORMATION FOR SEQ ID NO: 115:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 20 amino acids

(B) TYPE: amino acid

( C ) STRANDEDNESS :

( D ) TOPOLOGY : linear

( xi ) SEQUENCE DESCRI PTION : SEQ I D NO : 115 :

Asp Pro Val Asp Ala Val He Asn Thr Thr Cys Asn Tyr Gl y Gin Val 1 5 10 15

Val Ala Ala Leu 20

(2) INFORMATION FOR SEQ ID NO: 116: SEQUENCE CHARACTERISTICS:

(A) LENGTH: 15 ammo acids

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 116:

Ala Val Glu Ser Gly Met Leu Ala Leu Gly Thr Pro Ala Pro Ser 1 5 10 15

(2) INFORMATION FOR SEQ ID NO: 117:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 19 ammo acids

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 117:

Ala Ala Met Lys Pro Arg Thr Gly Asp Gly Pro Leu Glu Ala Ala Lys 1 5 10 15

Glu Gly Arg

(2) INFORMATION FOR SEQ ID NO: 118:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 15 ammo acids

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(x ) SEQUENCE DESCRIPTION: SEQ ID NO: 118:

Tyr Tyr Trp Cys Pro Gly Gin Pro Phe Asp Pro Ala Trp Gly Pro 1 5 10 15

(2) INFORMATION FOR SEQ ID NO: 119:

(l) SEQUENCE CHARACTERISTICS: (A) LENGTH: 14 ammo acids

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 119:

Asp He Gly Ser Glu Ser Thr Glu Asp Gin Gin Xaa Ala Val 1 5 10

(2) INFORMATION FOR SEQ ID NO: 120:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 13 ammo acids

(B) TYPE: amino acid

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 120:

Ala Glu Glu Ser He Ser Thr Xaa Glu Xaa He Val Pro 1 5 10

(2) INFORMATION FOR SEQ ID NO: 121:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 17 ammo acids

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 121:

Asp Pro Glu Pro Ala Pro Pro Val Pro Thr Thr Ala Ala Ser Pro Pro 1 5 10 15

Ser

(2) INFORMATION FOR SEQ ID NO: 122:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 15 ammo acids (B) TYPE: amino acid

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 122:

Ala Pro Lys Thr Tyr Xaa Glu Glu Leu Lys Gly Thr Asp Thr Gly 1 5 10 15

(2) INFORMATION FOR SEQ ID NO: 123:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 30 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 123:

Asp Pro Ala Ser Ala Pro Asp Val Pro Thr Ala Ala Gin Leu Thr Ser 1 5 10 15

Leu Leu Asn Ser Leu Ala Asp Pro Asn Val Ser Phe Ala Asn 20 25 30

(2) INFORMATION FOR SEQ ID NO: 124:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 22 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 124:

Asp Pro Pro Asp Pro His Gin Xaa Asp Met Thr Lys Gly Tyr Tyr Pro 1 5 10 15

Gly Gly Arg Arg Xaa Phe 20

(2) INFORMATION FOR SEQ ID NO: 125: (l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 7 amino acids

(B) TYPE: ammo acid

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 125:

Asp Pro Gly Tyr Thr Pro Gly 1 5

(2) INFORMATION FOR SEQ ID NO: 126:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 10 ammo acids

(B) TYPE: amino acid

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(IX) FEATURE:

(D) OTHER INFORMATION: /note= "The Second Residue Can Be Either a Pro or Thr"

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 126:

Xaa Xaa Gly Phe Thr Gly Pro Gin Phe Tyr 1 5 10

(2) INFORMATION FOR SEQ ID NO: 127:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 9 amino acids

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(ix) FEATURE:

(D) OTHER INFORMATION: /note= "The Third Residue Can Be Either a Gin or Leu"

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 127:

Xaa Pro Xaa Val Thr Ala Tyr Ala Gly 1 5 (2) INFORMATION FOR SEQ ID NO: 128:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 9 amino acids

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 128:

Xaa Xaa Xaa Glu Lys Pro Phe Leu Arg 1 5

(2) INFORMATION FOR SEQ ID NO: 129:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 15 ammo acids

(B) TYPE: amino ac d

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 129:

Xaa Asp Ser Glu Lys Ser Ala Thr He Lys Val Thr Asp Ala Ser 1 5 10 15

(2) INFORMATION FOR SEQ ID NO: 130:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 15 ammo acids

(B) TYPE: ammo acid

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 130:

Ala Gly Asp Thr Xaa He Tyr He Val Gly Asn Leu Thr Ala Asp 1 5 10 15

(2) INFORMATION FOR SEQ ID NO: 131:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 15 ammo acids (B) TYPE: amino acid

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 131:

Ala Pro Glu Ser Gly Ala Gly Leu Gly Gly Thr Val Gin Ala Gly 1 5 10 15

(2) INFORMATION FOR SEQ ID NO: 132:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 21 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi ) SEQUENCE DESCRIPTION : SEQ ID NO : 132 :

Xaa Tyr He Ala Tyr Xaa Thr Thr Ala Gly He Val Pro Gly Lys He 1 5 10 15

Asn Val His Leu Val 20

(2) INFORMATION FOR SEQ ID NO: 133:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 882 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: DNA (genomic)

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 133:

GCAACGCTGT CGTGGCCTTT GCGGTGATCG GTTTCGCCTC GCTGGCGGTG GCGGTGGCGG 60

TCACCATCCG ACCGACCGCG GCCTCAAAAC CGGTAGAGGG ACACCAAAAC GCCCAGCCAG 120

GGAAGTTCAT GCCGTTGTTG CCGACGCAAC AGCAGGCGCC GGTCCCGCCG CCTCCGCCCG 180

ATGATCCCAC CGCTGGATTC CAGGGCGGCA CCATTCCGGC TGTACAGAAC GTGGTGCCGC 240 GGCCGGGTAC CTCACCCGGG GTGGGTGGGA CGCCGGCTTC GCCTGCGCCG GAAGCGCCGG 300

CCGTGCCCGG TGTTGTGCCT GCCCCGGTGC CAATCCCGGT CCCGATCATC ATTCCCCCGT 360

TCCCGGGTTG GCAGCCTGGA ATGCCGACCA TCCCCACCGC ACCGCCGACG ACGCCGGTGA 420

CCACGTCGGC GACGACGCCG CCGACCACGC CGCCGACCAC GCCGGTGACC ACGCCGCCAA 480

CGACGCCGCC GACCACGCCG GTGACCACGC CGCCAACGAC GCCGCCGACC ACGCCGGTGA 540

CCACGCCACC AACGACCGTC GCCCCGACGA CCGTCGCCCC GACGACGGTC GCTCCGACCA 600

CCGTCGCCCC GACCACGGTC GCTCCAGCCA CCGCCACGCC GACGACCGTC GCTCCGCAGC 660

CGACGCAGCA GCCCACGCAA CAACCAACCC AACAGATGCC AACCCAGCAG CAGACCGTGG 720

CCCCGCAGAC GGTGGCGCCG GCTCCGCAGC CGCCGTCCGG TGGCCGCAAC GGCAGCGGCG 780

GGGGCGACTT ATTCGGCGGG TTCTGATCAC GGTCGCGGCT TCACTACGGT CGGAGGACAT 840

GGCCGGTGAT GCGGTGACGG TGGTGCTGCC CTGTCTCAAC GA 882 (2) INFORMATION FOR SEQ ID NO: 134:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 815 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: DNA (genomic)

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 134:

CCATCAACCA ACCGCTCGCG CCGCCCGCGC CGCCGGATCC GCCGTCGCCG CCACGCCCGC 60

CGGTGCCTCC GGTGCCCCCG TTGCCGCCGT CGCCGCCGTC GCCGCCGACC GGCTGGGTGC 120

CTAGGGCGCT GTTACCGCCC TGGTTGGCGG GGACGCCGCC GGCACCACCG GTACCGCCGA 180

TGGCGCCGTT GCCGCCGGCG GCACCGTTGC CACCGTTGCC ACCGTTGCCA CCGTTGCCGA 240

CCAGCCACCC GCCGCGACCA CCGGCACCGC CGGCGCCGCC CGCACCGCCG GCGTGCCCGT 300

TCGTGCCCGT ACCGCCGGCA CCGCCGTTGC CGCCGTCACC GCCGACGGAA CTACCGGCGG 360

ACGCGGCCTG CCCGCCGGCG CCGCCCGCAC CGCCATTGGC ACCGCCGTCA CCGCCGGCTG 420

GGAGTGCCGC GATTAGGGCA CTGACCGGCG CAACCAGCGC AAGTACTCTC GGTCACCGAG 480

CACTTCCAGA CGACACCACA GCACGGGGTT GTCGGCGGAC TGGGTGAAAT GGCAGCCGAT 540 AGCGGCTAGC TGTCGGCTGC GGTCAACCTC GATCATGATG TCGAGGTGAC CGTGACCGCG 600

CCCCCCGAAG GAGGCGCTGA ACTCGGCGTT GAGCCGATCG GCGATCGGTT GGGGCAGTGC 660

CCAGGCCAAT ACGGGGATAC CGGGTGTCNA AGCCGCCGCG AGCGCAGCTT CGGTTGCGCG 720

ACNGTGGTCG GGGTGGCCTG TTACGCCGTT GTCNTCGAAC ACGAGTAGCA GGTCTGCTCC 780

GGCGAGGGCA TCCACCACGC GTTGCGTCAG CTCGT 815 (2) INFORMATION FOR SEQ ID NO: 135:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1152 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: DNA (genomic)

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 135:

ACCAGCCGCC GGCTGAGGTC TCAGATCAGA GAGTCTCCGG ACTCACCGGG GCGGTTCAGC 60

CTTCTCCCAG AACAACTGCT GAAGATCCTC GCCCGCGAAA CAGGCGCTGA TTTGACGCTC 120

TATGACCGGT TGAACGACGA GATCATCCGG CAGATTGATA TGGCACCGCT GGGCTAACAG 180

GTGCGCAAGA TGGTGCAGCT GTATGTCTCG GACTCCGTGT CGCGGATCAG CTTTGCCGAC 240

GGCCGGGTGA TCGTGTGGAG CGAGGAGCTC GGCGAGAGCC AGTATCCGAT CGAGACGCTG 300

GACGGCATCA CGCTGTTTGG GCGGCCGACG ATGACAACGC CCTTCATCGT TGAGATGCTC 360

AAGCGTGAGC GCGACATCCA GCTCTTCACG ACCGACGGCC ACTACCAGGG CCGGATCTCA 420

ACACCCGACG TGTCATACGC GCCGCGGCTC CGTCAGCAAG TTCACCGCAC CGACGATCCT 480

GCGTTCTGCC TGTCGTTAAG CAAGCGGATC GTGTCGAGGA AGATCCTGAA TCAGCAGGCC 540

TTGATTCGGG CACACACGTC GGGGCAAGAC GTTGCTGAGA GCATCCGCAC GATGAAGCAC 600

TCGCTGGCCT GGGTCGATCG ATCGGGCTCC CTGGCGGAGT TGAACGGGTT CGAGGGAAAT 660

GCCGCAAAGG CATACTTCAC CGCGCTGGGG CATCTCGTCC CGCAGGAGTT CGCATTCCAG 720

GGCCGCTCGA CTCGGCCGCC GTTGGACGCC TTCAACTCGA TGGTCAGCCT CGGCTATTCG 780

CTGCTGTACA AGAACATCAT AGGGGCGATC GAGCGTCACA GCCTGAACGC GTATATCGGT 840

TTCCTACACC AGGATTCACG AGGGCACGCA ACGTCTCGTG CCGAATTCGG CACGAGCTCC 900 GCTGAAACCG CTGGCCGGCT GCTCAGTGCC CGTACGTAAT CCGCTGCGCC CAGGCCGGCC 960

CGCCGGCCGA ATACCAGCAG ATCGGACAGC GAATTGCCGC CCAGCCGGTT GGAGCCGTGC 1020

ATACCGCCGG CACACTCACC GGCAGCGAAC AGGCCTGGCA CCGTGGCGGC GCCGGTGTCC 1080

GCGTCTACTT CGACACCGCC CATCACGTAG TGACACGTCG GCCCGACTTC CATTGCCTGC 1140

GTTCGGCACG AG 1152 (2) INFORMATION FOR SEQ ID NO: 136:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 655 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: DNA (genomic)

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 136:

CTCGTGCCGA TTCGGCAGGG TGTACTTGCC GGTGGTGTAN GCCGCATGAG TGCCGACGAC 60

CAGCAATGCG GCAACAGCAC GGATCCCGGT CAACGACGCC ACCCGGTCCA CGTGGGCGAT 120

CCGCTCGAGT CCGCCCTGGG CGGCTCTTTC CTTGGGCAGG GTCATCCGAC GTGTTTCCGC 180

CGTGGTTTGC CGCCATTATG CCGGCGCGCC GCGTCGGGCG GCCGGTATGG CCGAANGTCG 240

ATCAGCACAC CCGAGATACG GGTCTGTGCA AGCTTTTTGA GCGTCGCGCG GGGCAGCTTC 300

GCCGGCAATT CTACTAGCGA GAAGTCTGGC CCGATACGGA TCTGACCGAA GTCGCTGCGG 360

TGCAGCCCAC CCTCATTGGC GATGGCGCCG ACGATGGCGC CTGGACCGAT CTTGTGCCGC 420

TTGCCGACGG CGACGCGGTA GGTGGTCAAG TCCGGTCTAC GCTTGGGCCT TTGCGGACGG 480

TCCCGACGCT GGTCGCGGTT GCGCCGCGAA AGCGGCGGGT CGGGTGCCAT CAGGAATGCC 540

TCACCGCCGC GGCACTGCAC GGCCAGTGCC GCGGCGATGT CAGCCATCGG GACATCATGC 600

TCGCGTTCAT ACTCCTCGAC CAGTCGGCGG AACAGCTCGA TTCCCGGACC GCCCA 655 (2) INFORMATION FOR SEQ ID NO: 137:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 267 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 137:

Asn Ala Val Val Ala Phe Ala Val He Gly Phe Ala Ser Leu Ala Val 1 5 10 15

Ala Val Ala Val Thr He Arg Pro Thr Ala Ala Ser Lys Pro Val Glu 20 25 30

Gly His Gin Asn Ala Gin Pro Gly Lys Phe Met Pro Leu Leu Pro Thr 35 40 45

Gin Gin Gin Ala Pro Val Pro Pro Pro Pro Pro Asp Asp Pro Thr Ala 50 55 60

Gly Phe Gin Gly Gly Thr He Pro Ala Val Gin Asn Val Val Pro Arg 65 70 75 80

Pro Gly Thr Ser Pro Gly Val Gly Gly Thr Pro Ala Ser Pro Ala Pro 85 90 95

Glu Ala Pro Ala Val Pro Gly Val Val Pro Ala Pro Val Pro He Pro 100 105 110

Val Pro He He He Pro Pro Phe Pro Gly Trp Gin Pro Gly Met Pro 115 120 125

Thr He Pro Thr Ala Pro Pro Thr Thr Pro Val Thr Thr Ser Ala Thr 130 135 140

Thr Pro Pro Thr Thr Pro Pro Thr Thr Pro Val Thr Thr Pro Pro Thr 145 150 155 160

Thr Pro Pro Thr Thr Pro Val Thr Thr Pro Pro Thr Thr Pro Pro Thr 165 170 175

Thr Pro Val Thr Thr Pro Pro Thr Thr Val Ala Pro Thr Thr Val Ala 180 185 190

Pro Thr Thr Val Ala Pro Thr Thr Val Ala Pro Thr Thr Val Ala Pro 195 200 205

Ala Thr Ala Thr Pro Thr Thr Val Ala Pro Gin Pro Thr Gin Gin Pro 210 215 220

Thr Gin Gin Pro Thr Gin Gin Met Pro Thr Gin Gin Gin Thr Val Ala 225 230 235 240

Pro Gin Thr Val Ala Pro Ala Pro Gin Pro Pro Ser Gly Gly Arg Asn 245 250 255 Gly Ser Gly Gly Gly Asp Leu Phe Gly Gly Phe 260 265

(2) INFORMATION FOR SEQ ID NO: 138:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 174 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: peptide

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 138:

He Asn Gin Pro Leu Ala Pro Pro Ala Pro Pro Asp Pro Pro Ser Pro 1 5 10 15

Pro Arg Pro Pro Val Pro Pro Val Pro Pro Leu Pro Pro Ser Pro Pro 20 25 30

Ser Pro Pro Thr Gly Trp Val Pro Arg Ala Leu Leu Pro Pro Trp Leu 35 40 45

Ala Gly Thr Pro Pro Ala Pro Pro Val Pro Pro Met Ala Pro Leu Pro 50 55 60

Pro Ala Ala Pro Leu Pro Pro Leu Pro Pro Leu Pro Pro Leu Pro Thr 65 70 75 80

Ser His Pro Pro Arg Pro Pro Ala Pro Pro Ala Pro Pro Ala Pro Pro 85 90 95

Ala Cys Pro Phe Val Pro Val Pro Pro Ala Pro Pro Leu Pro Pro Ser 100 105 110

Pro Pro Thr Glu Leu Pro Ala Asp Ala Ala Cys Pro Pro Ala Pro Pro 115 120 125

Ala Pro Pro Leu Ala Pro Pro Ser Pro Pro Ala Gly Ser Ala Ala He 130 135 140

Arg Ala Leu Thr Gly Ala Thr Ser Ala Ser Thr Leu Gly His Arg Ala 145 150 155 160

Leu Pro Asp Asp Thr Thr Ala Arg Gly Cys Arg Arg Thr Gly 165 170

(2) INFORMATION FOR SEQ ID NO: 139:

(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 35 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: peptide

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 139:

Gin Pro Pro Ala Glu Val Ser Asp Gin Arg Val Ser Gly Leu Thr Gly 1 5 10 15

Ala Val Gin Pro Ser Pro Arg Thr Thr Ala Glu Asp Pro Arg Pro Arg 20 25 30

Asn Arg Arg 35

(2) INFORMATION FOR SEQ ID NO: 140:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 104 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: peptide

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 140:

Arg Ala Asp Ser Ala Gly Cys Thr Cys Arg Trp Cys Xaa Pro His Glu 1 5 10 15

Cys Arg Arg Pro Ala Met Arg Gin Gin His Gly Ser Arg Ser Thr Thr 20 25 30

Pro Pro Gly Pro Arg Gly Arg Ser Ala Arg Val Arg Pro Gly Arg Leu 35 40 45

Phe Pro Trp Ala Gly Ser Ser Asp Val Phe Pro Pro Trp Phe Ala Ala 50 55 60

He Met Pro Ala Arg Arg Val Gly Arg Pro Val Trp Pro Xaa Val Asp 65 70 75 80

Gin His Thr Arg Asp Thr Gly Leu Cys Lys Leu Phe Glu Arg Arg Ala 85 90 95

Gly Gin Leu Arg Arg Gin Phe Tyr 100 (2) INFORMATION FOR SEQ ID NO: 141:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 53 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: other nucleic acid

(A) DESCRIPTION: /desc = "PCR primer"

(vi) ORIGINAL SOURCE:

(A) ORGANISM: Mycobacterium tuberculosis

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 141: GGATCCATAT GGGCCATCAT CATCATCATC ACGTGATCGA CATCATCGGG ACC 53

(2) INFORMATION FOR SEQ ID NO: 142:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 42 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: other nucleic acid

(A) DESCRIPTION: /desc = "PCR Primer"

(vi) ORIGINAL SOURCE:

(A) ORGANISM: Mycobacterium tuberculosis

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 142: CCTGAATTCA GGCCTCGGTT GCGCCGGCCT CATCTTGAAC GA 42

(2) INFORMATION FOR SEQ ID NO: 143:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 31 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: other nucleic acid

(A) DESCRIPTION: /desc = "PCR Primer"

(vi) ORIGINAL SOURCE:

(A) ORGANISM: Mycobacterium tuberculosis (xi) SEQUENCE DESCRIPTION: SEQ ID NO:143: GGATCCTGCA GGCTCGAAAC CACCGAGCGG T 31

(2) INFORMATION FOR SEQ ID NO: 144:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 31 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: other nucleic acid

(A) DESCRIPTION: /desc = "PCR primer"

(vi) ORIGINAL SOURCE:

(A) ORGANISM: Mycobacterium tuberculosis

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 144: CTCTGAATTC AGCGCTGGAA ATCGTCGCGA T 31

(2) INFORMATION FOR SEQ ID NO: 145:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 33 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: other nucleic acid

(A) DESCRIPTION: /desc = "PCR primer"

(vi) ORIGINAL SOURCE:

(A) ORGANISM: Mycobacterium tuberculosis

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 145: GGATCCAGCG CTGAGATGAA GACCGATGCC GCT 33

(2) INFORMATION FOR SEQ ID NO: 146:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 33 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear (11) MOLECULE TYPE: other nucleic acid

(A) DESCRIPTION: /desc = "PCR primer"

(vi) ORIGINAL SOURCE:

(A) ORGANISM: Mycobacterium tuberculosis

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 146: GAGAGAATTC TCAGAAGCCC ATTTGCGAGG ACA 33

(2) INFORMATION FOR SEQ ID NO: 147:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1993 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(ii) MOLECULE TYPE: DNA (genomic)

(vi) ORIGINAL SOURCE:

(A) ORGANISM: Mycobacterium tuberculosis

(ix) FEATURE:

(A) NAME/KEY: CDS

(B) LOCATION: 152..1273

(x ) SEQUENCE DESCRIPTION: SEQ ID NO: 147:

TGTTCTTCGA CGGCAGGCTG GTGGAGGAAG GGCCCACCGA ACAGCTGTTC TCCTCGCCGA 60

AGCATGCGGA AACCGCCCGA TACGTCGCCG GACTGTCGGG GGACGTCAAG GACGCCAAGC 120

GCGGAAATTG AAGAGCACAG AAAGGTATGG C GTG AAA ATT CGT TTG CAT ACG 172 1 5

CTG TTG GCC GTG TTG ACC GCT GCG CCG CTG CTG CTA GCA GCG GCG GGC 220 Leu Leu Ala Val Leu Thr Ala Ala Pro Leu Leu Leu Ala Ala Ala Gly 10 15 20

TGT GGC TCG AAA CCA CCG AGC GGT TCG CCT GAA ACG GGC GCC GGC GCC 268 Cys Gly Ser Lys Pro Pro Ser Gly Ser Pro Glu Thr Gly Ala Gly Ala 25 30 35

GGT ACT GTC GCG ACT ACC CCC GCG TCG TCG CCG GTG ACG TTG GCG GAG 316 Gly Thr Val Ala Thr Thr Pro Ala Ser Ser Pro Val Thr Leu Ala Glu 40 45 50 55

ACC GGT AGC ACG CTG CTC TAC CCG CTG TTC AAC CTG TGG GGT CCG GCC 364 Thr Gly Ser Thr Leu Leu Tyr Pro Leu Phe Asn Leu Trp Gly Pro Ala 60 65 70 TTT CAC GAG AGG TAT CCG AAC GTC ACG ATC ACC GCT CAG GGC ACC GGT 412 Phe His Glu Arg Tyr Pro Asn Val Thr He Thr Ala Gin Gly Thr Gly 75 80 85

TCT GGT GCC GGG ATC GCG CAG GCC GCC GCC GGG ACG GTC AAC ATT GGG 460 Ser Gly Ala Gly He Ala Gin Ala Ala Ala Gly Thr Val Asn He Gly 90 95 100

GCC TCC GAC GCC TAT CTG TCG GAA GGT GAT ATG GCC GCG CAC AAG GGG 508 Ala Ser Asp Ala Tyr Leu Ser Glu Gly Asp Met Ala Ala His Lys Gly 105 110 115

CTG ATG AAC ATC GCG CTA GCC ATC TCC GCT CAG CAG GTC AAC TAC AAC 556 Leu Met Asn He Ala Leu Ala He Ser Ala Gin Gin Val Asn Tyr Asn 120 125 130 135

CTG CCC GGA GTG AGC GAG CAC CTC AAG CTG AAC GGA AAA GTC CTG GCG 604 Leu Pro Gly Val Ser Glu His Leu Lys Leu Asn Gly Lys Val Leu Ala 140 145 150

GCC ATG TAC CAG GGC ACC ATC AAA ACC TGG GAC GAC CCG CAG ATC GCT 652 Ala Met Tyr Gin Gly Thr He Lys Thr Trp Asp Asp Pro Gin He Ala 155 160 165

GCG CTC AAC CCC GGC GTG AAC CTG CCC GGC ACC GCG GTA GTT CCG CTG 700 Ala Leu Asn Pro Gly Val Asn Leu Pro Gly Thr Ala Val Val Pro Leu 170 175 180

CAC CGC TCC GAC GGG TCC GGT GAC ACC TTC TTG TTC ACC CAG TAC CTG 748 His Arg Ser Asp Gly Ser Gly Asp Thr Phe Leu Phe Thr Gin Tyr Leu 185 190 195

TCC AAG CAA GAT CCC GAG GGC TGG GGC AAG TCG CCC GGC TTC GGC ACC 796 Ser Lys Gin Asp Pro Glu Gly Trp Gly Lys Ser Pro Gly Phe Gly Thr 200 205 210 215

ACC GTC GAC TTC CCG GCG GTG CCG GGT GCG CTG GGT GAG AAC GGC AAC 844 Thr Val Asp Phe Pro Ala Val Pro Gly Ala Leu Gly Glu Asn Gly Asn 220 225 230

GGC GGC ATG GTG ACC GGT TGC GCC GAG ACA CCG GGC TGC GTG GCC TAT 892 Gly Gly Met Val Thr Gly Cys Ala Glu Thr Pro Gly Cys Val Ala Tyr 235 240 245

ATC GGC ATC AGC TTC CTC GAC CAG GCC AGT CAA CGG GGA CTC GGC GAG 940 He Gly He Ser Phe Leu Asp Gin Ala Ser Gin Arg Gly Leu Gly Glu 250 255 260

GCC CAA CTA GGC AAT AGC TCT GGC AAT TTC TTG TTG CCC GAC GCG CAA 988 Ala Gin Leu Gly Asn Ser Ser Gly Asn Phe Leu Leu Pro Asp Ala Gin 265 270 275

AGC ATT CAG GCC GCG GCG GCT GGC TTC GCA TCG AAA ACC CCG GCG AAC 1036 Ser He Gin Ala Ala Ala Ala Gly Phe Ala Ser Lys Thr Pro Ala Asn 280 285 290 295

CAG GCG ATT TCG ATG ATC GAC GGG CCC GCC CCG GAC GGC TAC CCG ATC 1084 Gin Ala He Ser Met He Asp Gly Pro Ala Pro Asp Gly Tyr Pro He 300 305 310

ATC AAC TAC GAG TAC GCC ATC GTC AAC AAC CGG CAA AAG GAC GCC GCC 1132 He Asn Tyr Glu Tyr Ala He Val Asn Asn Arg Gin Lys Asp Ala Ala 315 320 325

ACC GCG CAG ACC TTG CAG GCA TTT CTG CAC TGG GCG ATC ACC GAC GGC 1180 Thr Ala Gin Thr Leu Gin Ala Phe Leu His Trp Ala He Thr Asp Gly 330 335 340

AAC AAG GCC TCG TTC CTC GAC CAG GTT CAT TTC CAG CCG CTG CCG CCC 1228 Asn Lys Ala Ser Phe Leu Asp Gin Val His Phe Gin Pro Leu Pro Pro 345 350 355

GCG GTG GTG AAG TTG TCT GAC GCG TTG ATC GCG ACG ATT TCC AGC 1273

Ala Val Val Lys Leu Ser Asp Ala Leu He Ala Thr He Ser Ser 360 365 370

TAGCCTCGTT GACCACCACG CGACAGCAAC CTCCGTCGGG CCATCGGGCT GCTTTGCGGA 1333

GCATGCTGGC CCGTGCCGGT GAACTCGGCC GCGCTGGCCC GGCCATCCGG TGGTTGGGTG 1393

GGATAGGTGC GGTGATCCCG CTGCTTGCGC TGGTCTTGGT GCTGGTGGTG CTGGTCATCG 1453

AGGCGATGGG TGCGATCAGG CTCAACGGGT TGCATTTCTT CACCGCCACC GAATGGAATC 1513

CAGGCAACAC CTACGGCGAA ACCGTTGTCA CCGACGCGTC GCCCATCCGG TCGGCGCCTA 1573

CTACGGGGCG TTGCCGCTGA TCGTCGGGAC GCTGGCGACC TCGGCAATCG CCCTGATCAT 1633

CGCGGTGCCG GTCTCTGTAG GAGCGGCGCT GGTGATCGTG GAACGGCTGC CGAAACGGTT 1693

GGCCGAGGCT GTGGGAATAG TCCTGGAATT GCTCGCCGGA ATCCCCAGCG TGGTCGTCGG 1753

TTTGTGGGGG GCAATGACGT TCGGGCCGTT CATCGCTCAT CACATCGCTC CGGTGATCGC 1813

TCACAACGCT CCCGATGTGC CGGTGCTGAA CTACTTGCGC GGCGACCCGG GCAACGGGGA 1873

GGGCATGTTG GTGTCCGGTC TGGTGTTGGC GGTGATGGTC GTTCCCATTA TCGCCACCAC 1933

CACTCATGAC CTGTTCCGGC AGGTGCCGGT GTTGCCCCGG GAGGGCGCGA TCGGGAATTC 1993

(2) INFORMATION FOR SEQ ID NO: 148:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 374 ammo acids (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 148:

Val Lys He Arg Leu His Thr Leu Leu Ala Val Leu Thr Ala Ala Pro 1 5 10 15

Leu Leu Leu Ala Ala Ala Gly Cys Gly Ser Lys Pro Pro Ser Gly Ser 20 25 30

Pro Glu Thr Gly Ala Gly Ala Gly Thr Val Ala Thr Thr Pro Ala Ser 35 40 45

Ser Pro Val Thr Leu Ala Glu Thr Gly Ser Thr Leu Leu Tyr Pro Leu 50 55 60

Phe Asn Leu Trp Gly Pro Ala Phe His Glu Arg Tyr Pro Asn Val Thr 65 70 75 80

He Thr Ala Gin Gly Thr Gly Ser Gly Ala Gly He Ala Gin Ala Ala 85 90 95

Ala Gly Thr Val Asn He Gly Ala Ser Asp Ala Tyr Leu Ser Glu Gly 100 105 110

Asp Met Ala Ala His Lys Gly Leu Met Asn He Ala Leu Ala He Ser 115 120 125

Ala Gin Gin Val Asn Tyr Asn Leu Pro Gly Val Ser Glu His Leu Lys 130 135 140

Leu Asn Gly Lys Val Leu Ala Ala Met Tyr Gin Gly Thr He Lys Thr 145 150 155 160

Trp Asp Asp Pro Gin He Ala Ala Leu Asn Pro Gly Val Asn Leu Pro 165 170 175

Gly Thr Ala Val Val Pro Leu His Arg Ser Asp Gly Ser Gly Asp Thr 180 185 190

Phe Leu Phe Thr Gin Tyr Leu Ser Lys Gin Asp Pro Glu Gly Trp Gly 195 200 205

Lys Ser Pro Gly Phe Gly Thr Thr Val Asp Phe Pro Ala Val Pro Gly 210 215 220

Ala Leu Gly Glu Asn Gly Asn Gly Gly Met Val Thr Gly Cys Ala Glu 225 230 235 240

Thr Pro Gly Cys Val Ala Tyr He Gly He Ser Phe Leu Asp Gin Ala 245 250 255

Ser Gin Arg Gly Leu Gly Glu Ala Gin Leu Gly Asn Ser Ser Gly Asn 260 265 270 Phe Leu Leu Pro Asp Ala Gin Ser He Gin Ala Ala Ala Ala Gly Phe 275 280 285

Ala Ser Lys Thr Pro Ala Asn Gin Ala He Ser Met He Asp Gly Pro 290 295 300

Ala Pro Asp Gly Tyr Pro He He Asn Tyr Glu Tyr Ala He Val Asn 305 310 315 320

Asn Arg Gin Lys Asp Ala Ala Thr Ala Gin Thr Leu Gin Ala Phe Leu 325 330 335

His Trp Ala He Thr Asp Gly Asn Lys Ala Ser Phe Leu Asp Gin Val 340 345 350

His Phe Gin Pro Leu Pro Pro Ala Val Val Lys Leu Ser Asp Ala Leu 355 360 365

He Ala Thr He Ser Ser 370

(2) INFORMATION FOR SEQ ID NO: 149:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1993 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 149:

TGTTCTTCGA CGGCAGGCTG GTGGAGGAAG GGCCCACCGA ACAGCTGTTC TCCTCGCCGA 60

AGCATGCGGA AACCGCCCGA TACGTCGCCG GACTGTCGGG GGACGTCAAG GACGCCAAGC 120

GCGGAAATTG AAGAGCACAG AAAGGTATGG CGTGAAAATT CGTTTGCATA CGCTGTTGGC 180

CGTGTTGACC GCTGCGCCGC TGCTGCTAGC AGCGGCGGGC TGTGGCTCGA AACCACCGAG 240

CGGTTCGCCT GAAACGGGCG CCGGCGCCGG TACTGTCGCG ACTACCCCCG CGTCGTCGCC 300

GGTGACGTTG GCGGAGACCG GTAGCACGCT GCTCTACCCG CTGTTCAACC TGTGGGGTCC 360

GGCCTTTCAC GAGAGGTATC CGAACGTCAC GATCACCGCT CAGGGCACCG GTTCTGGTGC 420

CGGGATCGCG CAGGCCGCCG CCGGGACGGT CAACATTGGG GCCTCCGACG CCTATCTGTC 480

GGAAGGTGAT ATGGCCGCGC ACAAGGGGCT GATGAACATC GCGCTAGCCA TCTCCGCTCA 540

GCAGGTCAAC TACAACCTGC CCGGAGTGAG CGAGCACCTC AAGCTGAACG GAAAAGTCCT 600 GGCGGCCATG TACCAGGGCA CCATCAAAAC CTGGGACGAC CCGCAGATCG CTGCGCTCAA 660

CCCCGGCGTG AACCTGCCCG GCACCGCGGT AGTTCCGCTG CACCGCTCCG ACGGGTCCGG 720

TGACACCTTC TTGTTCACCC AGTACCTGTC CAAGCAAGAT CCCGAGGGCT GGGGCAAGTC 780

GCCCGGCTTC GGCACCACCG TCGACTTCCC GGCGGTGCCG GGTGCGCTGG GTGAGAACGG 840

CAACGGCGGC ATGGTGACCG GTTGCGCCGA GACACCGGGC TGCGTGGCCT ATATCGGCAT 900

CAGCTTCCTC GACCAGGCCA GTCAACGGGG ACTCGGCGAG GCCCAACTAG GCAATAGCTC 960

TGGCAATTTC TTGTTGCCCG ACGCGCAAAG CATTCAGGCC GCGGCGGCTG GCTTCGCATC 1020

GAAAACCCCG GCGAACCAGG CGATTTCGAT GATCGACGGG CCCGCCCCGG ACGGCTACCC 1080

GATCATCAAC TACGAGTACG CCATCGTCAA CAACCGGCAA AAGGACGCCG CCACCGCGCA 1140

GACCTTGCAG GCATTTCTGC ACTGGGCGAT CACCGACGGC AACAAGGCCT CGTTCCTCGA 1200

CCAGGTTCAT TTCCAGCCGC TGCCGCCCGC GGTGGTGAAG TTGTCTGACG CGTTGATCGC 1260

GACGATTTCC AGCTAGCCTC GTTGACCACC ACGCGACAGC AACCTCCGTC GGGCCATCGG 1320

GCTGCTTTGC GGAGCATGCT GGCCCGTGCC GGTGAAGTCG GCCGCGCTGG CCCGGCCATC 1380

CGGTGGTTGG GTGGGATAGG TGCGGTGATC CCGCTGCTTG CGCTGGTCTT GGTGCTGGTG 1440

GTGCTGGTCA TCGAGGCGAT GGGTGCGATC AGGCTCAACG GGTTGCATTT CTTCACCGCC 1500

ACCGAATGGA ATCCAGGCAA CACCTACGGC GAAACCGTTG TCACCGACGC GTCGCCCATC 1560

CGGTCGGCGC CTACTACGGG GCGTTGCCGC TGATCGTCGG GACGCTGGCG ACCTCGGCAA 1620

TCGCCCTGAT CATCGCGGTG CCGGTCTCTG TAGGAGCGGC GCTGGTGATC GTGGAACGGC 1680

TGCCGAAACG GTTGGCCGAG GCTGTGGGAA TAGTCCTGGA ATTGCTCGCC GGAATCCCCA 1740

GCGTGGTCGT CGGTTTGTGG GGGGCAATGA CGTTCGGGCC GTTCATCGCT CATCACATCG 1800

CTCCGGTGAT CGCTCACAAC GCTCCCGATG TGCCGGTGCT GAACTACTTG CGCGGCGACC 1860

CGGGCAACGG GGAGGGCATG TTGGTGTCCG GTCTGGTGTT GGCGGTGATG GTCGTTCCCA 1920

TTATCGCCAC CACCACTCAT GACCTGTTCC GGCAGGTGCC GGTGTTGCCC CGGGAGGGCG 1980

CGATCGGGAA TTC 1993 (2) INFORMATION FOR SEQ ID NO: 150:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 374 amino acids

(B) TYPE: amino acid

( C ) STRANDEDNESS :

( D ) TOPOLOGY : linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 150:

Met Lys He Arg Leu His Thr Leu Leu Ala Val Leu Thr Ala Ala Pro 1 5 10 15

Leu Leu Leu Ala Ala Ala Gly Cys Gly Ser Lys Pro Pro Ser Gly Ser 20 25 30

Pro Glu Thr Gly Ala Gly Ala Gly Thr Val Ala Thr Thr Pro Ala Ser 35 40 45

Ser Pro Val Thr Leu Ala Glu Thr Gly Ser Thr Leu Leu Tyr Pro Leu 50 55 60

Phe Asn Leu Trp Gly Pro Ala Phe His Glu Arg Tyr Pro Asn Val Thr 65 70 75 80

He Thr Ala Gin Gly Thr Gly Ser Gly Ala Gly He Ala Gin Ala Ala 85 90 95

Ala Gly Thr Val Asn He Gly Ala Ser Asp Ala Tyr Leu Ser Glu Gly 100 105 110

Asp Met Ala Ala His Lys Gly Leu Met Asn He Ala Leu Ala He Ser 115 120 125

Ala Gin Gin Val Asn Tyr Asn Leu Pro Gly Val Ser Glu His Leu Lys 130 135 140

Leu Asn Gly Lys Val Leu Ala Ala Met Tyr Gin Gly Thr He Lys Thr 145 150 155 160

Trp Asp Asp Pro Gin He Ala Ala Leu Asn Pro Gly Val Asn Leu Pro 165 170 175

Gly Thr Ala Val Val Pro Leu His Arg Ser Asp Gly Ser Gly Asp Thr 180 185 190

Phe Leu Phe Thr Gin Tyr Leu Ser Lys Gin Asp Pro Glu Gly Trp Gly 195 200 205

Lys Ser Pro Gly Phe Gly Thr Thr Val Asp Phe Pro Ala Val Pro Gly 210 215 220

Ala Leu Gly Glu Asn Gly Asn Gly Gly Met Val Thr Gly Cys Ala Glu 225 230 235 240

Thr Pro Gly Cys Val Ala Tyr He Gly He Ser Phe Leu Asp Gin Ala 245 250 255 Ser Gin Arg Gly Leu Gly Glu Ala Gin Leu Gly Asn Ser Ser Gly Asn 260 265 270

Phe Leu Leu Pro Asp Ala Gin Ser He Gin Ala Ala Ala Ala Gly Phe 275 280 285

Ala Ser Lys Thr Pro Ala Asn Gin Ala He Ser Met He Asp Gly Pro 290 295 300

Ala Pro Asp Gly Tyr Pro He He Asn Tyr Glu Tyr Ala He Val Asn 305 310 315 320

Asn Arg Gin Lys Asp Ala Ala Thr Ala Gin Thr Leu Gin Ala Phe Leu 325 330 335

His Trp Ala He Thr Asp Gly Asn Lys Ala Ser Phe Leu Asp Gin Val 340 345 350

His Phe Gin Pro Leu Pro Pro Ala Val Val Lys Leu Ser Asp Ala Leu 355 360 365

He Ala Thr He Ser Ser 370

(2) INFORMATION FOR SEQ ID NO: 151:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1777 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 151:

GGTCTTGACC ACCACCTGGG TGTCGAAGTC GGTGCCCGGA TTGAAGTCCA GGTACTCGTG 60

GGTGGGGCGG GCGAAACAAT AGCGACAAGC ATGCGAGCAG CCGCGGTAGC CGTTGACGGT 120

GTAGCGAAAC GGCAACGCGG CCGCGTTGGG CACCTTGTTC AGCGCTGATT TGCACAACAC 180

CTCGTGGAAG GTGATGCCGT CGAATTGTGG CGCGCGAACG CTGCGGACCA GGCCGATCCG 240

CTGCAACCCG GCAGCGCCCG TCGTCAACGG GCATCCCGTT CACCGCGACG GCTTGCCGGG 300

CCCAACGCAT ACCATTATTC GAACAACCGT TCTATACTTT GTCAACGCTG GCCGCTACCG 360

AGCGCCGCAC AGGATGTGAT ATGCCATCTC TGCCCGCACA GACAGGAGCC AGGCCTTATG 420

ACAGCATTCG GCGTCGAGCC CTACGGGCAG CCGAAGTACC TAGAAATCGC CGGGAAGCGC 480

ATGGCGTATA TCGACGAAGG CAAGGGTGAC GCCATCGTCT TTCAGCACGG CAACCCCACG 540 TCGTCTTACT TGTGGCGCAA CATCATGCCG CACTTGGAAG GGCTGGGCCG GCTGGTGGCC 600

TGCGATCTGA TCGGGATGGG CGCGTCGGAC AAGCTCAGCC CATCGGGACC CGACCGCTAT 660

AGCTATGGCG AGCAACGAGA CTTTTTGTTC GCGCTCTGGG ATGCGCTCGA CCTCGGCGAC 720

CACGTGGTAC TGGTGCTGCA CGACTGGGGC TCGGCGCTCG GCTTCGACTG GGCTAACCAG 780

CATCGCGACC GAGTGCAGGG GATCGCGTTC ATGGAAGCGA TCGTCACCCC GATGACGTGG 840

GCGGACTGGC CGCCGGCCGT GCGGGGTGTG TTCCAGGGTT TCCGATCGCC TCAAGGCGAG 900

CCAATGGCGT TGGAGCACAA CATCTTTGTC GAACGGGTGC TGCCCGGGGC GATCCTGCGA 960

CAGCTCAGCG ACGAGGAAAT GAACCACTAT CGGCGGCCAT TCGTGAACGG CGGCGAGGAC 1020

CGTCGCCCCA CGTTGTCGTG GCCACGAAAC CTTCCAATCG ACGGTGAGCC CGCCGAGGTC 1080

GTCGCGTTGG TCAACGAGTA CCGGAGCTGG CTCGAGGAAA CCGACATGCC GAAACTGTTC 1140

ATCAACGCCG AGCCCGGCGC GATCATCACC GGCCGCATCC GTGACTATGT CAGGAGCTGG 1200

CCCAACCAGA CCGAAATCAC AGTGCCCGGC GTGCATTTCG TTCAGGAGGA CAGCGATGGC 1260

GTCGTATCGT GGGCGGGCGC TCGGCAGCAT CGGCGACCTG GGAGCGCTCT CATTTCACGA 1320

GACCAAGAAT GTGATTTCCG GCGAAGGCGG CGCCCTGCTT GTCAACTCAT AAGACTTCCT 1380

GCTCCGGGCA GAGATTCTCA GGGAAAAGGG CACCAATCGC AGCCGCTTCC TTCGCAACGA 1440

GGTCGACAAA TATACGTGGC AGGACAAAGG TCTTCCTATT TGCCCAGCGA ATTAGTCGCT 1500

GCCTTTCTAT GGGCTCAGTT CGAGGAAGCC GAGCGGATCA CGCGTATCCG ATTGGACCTA 1560

TGGAACCGGT ATCATGAAAG CTTCGAATCA TTGGAACAGC GGGGGCTCCT GCGCCGTCCG 1620

ATCATCCCAC AGGGCTGCTC TCACAACGCC CACATGTACT ACGTGTTACT AGCGCCCAGC 1680

GCCGATCGGG AGGAGGTGCT GGCGCGTCTG ACGAGCGAAG GTATAGGCGC GGTCTTTCAT 1740

TACGTGCCGC TTCACGATTC GCCGGCCGGG CGTCGCT 1777 (2) INFORMATION FOR SEQ ID NO: 152:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 324 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 152:

GAGATTGAAT CGTACCGGTC TCCTTAGCGG CTCCGTCCCG TGAATGCCCA TATCACGCAC 60

GGCCATGTTC TGGCTGTCGA CCTTCGCCCC ATGCCCGGAC GTTGGTAAAC CCAGGGTTTG 120

ATCAGTAATT CCGGGGGACG GTTGCGGGAA GGCGGCCAGG ATGTGCGTGA GCCGCGGCGC 180

CGCCGTCGCC CAGGCGACCG CTGGATGCTC AGCCCCGGTG CGGCGACGTA GCCAGCGTTT 240

GGCGCGTGTC GTCCACAGTG GTACTCCGGT GACGACGCGG CGCGGTGCCT GGGTGAAGAC 300

CGTGACCGAC GCCGCCGATT CAGA 324 (2) INFORMATION FOR SEQ ID NO: 153:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1338 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 153:

GCGGTACCGC CGCGTTGCGC TGGCACGGGA CCTGTACGAC CTGAACCACT TCGCCTCGCG 60

AACGATTGAC GAACCGCTCG TGCGGCGGCT GTGGGTGCTC AAGGTGTGGG GTGATGTCGT 120

CGATGACCGG CGCGGCACCC GGCCACTACG CGTCGAAGAC GTCCTCGCCG CCCGCAGCGA 180

GCACGACTTC CAGCCCGACT CGATCGGCGT GCTGACCCGT CCTGTCGCTA TGGCTGCCTG 240

GGAAGCTCGC GTTCGGAAGC GATTTGCGTT CCTCACTGAC CTCGACGCCG ACGAGCAGCG 300

GTGGGCCGCC TGCGACGAAC GGCACCGCCG CGAAGTGGAG AACGCGCTGG CGGTGCTGCG 360

GTCCTGATCA ACCTGCCGGC GATCGTGCCG TTCCGCTGGC ACGGTTGCGG CTGGACGCGG 420

CTGAATCGAC TAGATGAGAG CAGTTGGGCA CGAATCCGGC TGTGGTGGTG AGCAAGACAC 480

GAGTACTGTC ATCACTATTG GATGCACTGG ATGACCGGCC TGATTCAGCA GGACCAATGG 540

AACTGCCCGG GGCAAAACGT CTCGGAGATG ATCGGCGTCC CCTCGGAACC CTGCGGTGCT 600

GGCGTCATTC GGACATCGGT CCGGCTCGCG GGATCGTGGT GACGCCAGCG CTGAAGGAGT 660

GGAGCGCGGC GGTGCACGCG CTGCTGGACG GCCGGCAGAC GGTGCTGCTG CGTAAGGGCG 720

GGATCGGCGA GAAGCGCTTC GAGGTGGCGG CCCACGAGTT CTTGTTGTTC CCGACGGTCG 780

CGCACAGCCA CGCCGAGCGG GTTCGCCCCG AGCACCGCGA CCTGCTGGGC CCGGCGGCCG 840 CCGACAGCAC CGACGAGTGT GTGCTACTGC GGGCCGCAGC GAAAGTTGTT GCCGCACTGC 900

CGGTTAACCG GCCAGAGGGT CTGGACGCCA TCGAGGATCT GCACATCTGG ACCGCCGAGT 960

CGGTGCGCGC CGACCGGCTC GACTTTCGGC CCAAGCACAA ACTGGCCGTC TTGGTGGTCT 1020

CGGCGATCCC GCTGGCCGAG CCGGTCCGGC TGGCGCGTAG GCCCGAGTAC GGCGGTTGCA 1080

CCAGCTGGGT GCAGCTGCCG GTGACGCCGA CGTTGGCGGC GCCGGTGCAC GACGAGGCCG 1140

CGCTGGCCGA GGTCGCCGCC CGGGTCCGCG AGGCCGTGGG TTGACTGGGC GGCATCGCTT 1200

GGGTCTGAGC TGTACGCCCA GTCGGCGCTG CGAGTGATCT GCTGTCGGTT CGGTCCCTGC 1260

TGGCGTCAAT TGACGGCGCG GGCAACAGCA GCATTGGCGG CGCCATCCTC CGCGCGGCCG 1320

GCGCCCACCG CTACAACC 1338 (2) INFORMATION FOR SEQ ID NO: 154:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 321 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 154:

CCGGCGGCAC CGGCGGCACC GGCGGTACCG GCGGCAACGG CGCTGACGCC GCTGCTGTGG 60

TGGGCTTCGG CGCGAACGGC GACCCTGGCT TCGCTGGCGG CAAAGGCGGT AACGGCGGAA 120

TAGGTGGGGC CGCGGTGACA GGCGGGGTCG CCGGCGACGG CGGCACCGGC GGCAAAGGTG 180

GCACCGGCGG TGCCGGCGGC GCCGGCAACG ACGCCGGCAG CACCGGCAAT CCCGGCGGTA 240

AGGGCGGCGA CGGCGGGATC GGCGGTGCCG GCGGGGCCGG CGGCGCGGCC GGCACCGGCA 300

ACGGCGGCCA TGCCGGCAAC C 321 (2) INFORMATION FOR SEQ ID NO: 155:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 492 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 155:

GAAGACCCGG CCCCGCCATA TCGATCGGCT CGCCGACTAC TTTCGCCGAA CGTGCACGCG 60

GCGGCGTCGG GCTGATCATC ACCGGTGGCT ACGCGCCCAA CCGCACCGGA TGGCTGCTGC 120

CGTTCGCCTC CGAACTCGTC ACTTCGGCGC AAGCCCGACG GCACCGCCGA ATCACCAGGG 180

CGGTCCACGA TTCGGGTGCA AAGATCCTGC TGCAAATCCT GCACGCCGGA CGCTACGCCT 240

ACCACCCACT TGCGGTCAGC GCCTCGCCGA TCAAGGCGCC GATCACCCCG TTTCGTCCGC 300

GAGCACTATC GGCTCGCGGG GTCGAAGCGA CCATCGCGGA TTTCGCCCGC TGCGCGCAGT 360

TGGCCCGCGA TGCCGGCTAC GACGGCGTCG AAATCATGGG CAGCGAAGGG TATCTGCTCA 420

ATCAGTTCCT GGCGCCGCGC ACCAACAAGC GCACCGACTC GTGGGGCGGC ACACCGGCCA 480 ACCGTCGCCG GT 492

(2) INFORMATION FOR SEQ ID NO: 156:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 536 ammo acids

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 156:

Phe Ala Gin His Leu Val Glu Gly Asp Ala Val Glu Leu Trp Arg Ala 1 5 10 15

Asn Ala Ala Asp Gin Ala Asp Pro Leu Gin Pro Gly Ser Ala Arg Arg 20 25 30

Gin Arg Ala Ser Arg Ser Pro Arg Arg Leu Ala Gly Pro Asn Ala Tyr 35 40 45

His Tyr Ser Asn Asn Arg Ser He Leu Cys Gin Arg Trp Pro Leu Pro 50 55 60

Ser Ala Ala Gin Asp Val He Cys His Leu Cys Pro His Arg Gin Glu 65 70 75 80

Pro Gly Leu Met Thr Ala Phe Gly Val Glu Pro Tyr Gly Gin Pro Lys 85 90 95

Tyr Leu Glu He Ala Gly Lys Arg Met Ala Tyr He Asp Glu Gly Lys 100 105 110

Gly Asp Ala He Val Phe Gin His Gly Asn Pro Thr Ser Ser Tyr Leu 115 120 125

Trp Arg Asn He Met Pro His Leu Glu Gly Leu Gly Arg Leu Val Ala 130 135 140

Cys Asp Leu He Gly Met Gly Ala Ser Asp Lys Leu Ser Pro Ser Gly 145 150 155 160

Pro Asp Arg Tyr Ser Tyr Gly Glu Gin Arg Asp Phe Leu Phe Ala Leu 165 170 175

Trp Asp Ala Leu Asp Leu Gly Asp His Val Val Leu Val Leu His Asp 180 185 190

Trp Gly Ser Ala Leu Gly Phe Asp Trp Ala Asn Gin His Arg Asp Arg 195 200 205

Val Gin Gly He Ala Phe Met Glu Ala He Val Thr Pro Met Thr Trp 210 215 220

Ala Asp Trp Pro Pro Ala Val Arg Gly Val Phe Gin Gly Phe Arg Ser 225 230 235 240

Pro Gin Gly Glu Pro Met Ala Leu Glu His Asn He Phe Val Glu Arg 245 250 255

Val Leu Pro Gly Ala He Leu Arg Gin Leu Ser Asp Glu Glu Met Asn 260 265 270

His Tyr Arg Arg Pro Phe Val Asn Gly Gly Glu Asp Arg Arg Pro Thr 275 280 285

Leu Ser Trp Pro Arg Asn Leu Pro He Asp Gly Glu Pro Ala Glu Val 290 295 300

Val Ala Leu Val Asn Glu Tyr Arg Ser Trp Leu Glu Glu Thr Asp Met 305 310 315 320

Pro Lys Leu Phe He Asn Ala Glu Pro Gly Ala He He Thr Gly Arg 325 330 335

He Arg Asp Tyr Val Arg Ser Trp Pro Asn Gin Thr Glu He Thr Val 340 345 350

Pro Gly Val His Phe Val Gin Glu Asp Ser Asp Gly Val Val Ser Trp 355 360 365

Ala Gly Ala Arg Gin His Arg Arg Pro Gly Ser Ala Leu He Ser Arg 370 375 380

Asp Gin Glu Cys Asp Phe Arg Arg Arg Arg Arg Pro Ala Cys Gin Leu 385 390 395 400 He Arg Leu Pro Ala Pro Gly Arg Asp Ser Gin Gly Lys Gly His Gin 405 410 415

Ser Gin Pro Leu Pro Ser Gin Arg Gly Arg Gin He Tyr Val Ala Gly 420 425 430

Gin Arg Ser Ser Tyr Leu Pro Ser Glu Leu Val Ala Ala Phe Leu Trp 435 440 445

Ala Gin Phe Glu Glu Ala Glu Arg He Thr Arg He Arg Leu Asp Leu 450 455 460

Trp Asn Arg Tyr His Glu Ser Phe Glu Ser Leu Glu Gin Arg Gly Leu 465 470 475 480

Leu Arg Arg Pro He He Pro Gin Gly Cys Ser His Asn Ala His Met 485 490 495

Tyr Tyr Val Leu Leu Ala Pro Ser Ala Asp Arg Glu Glu Val Leu Ala 500 505 510

Arg Leu Thr Ser Glu Gly He Gly Ala Val Phe His Tyr Val Pro Leu 515 520 525

His Asp Ser Pro Ala Gly Arg Arg 530 535

(2) INFORMATION FOR SEQ ID NO: 157:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 284 ammo acids

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi ) SEQUENCE DESCRIPTION: SEQ ID NO: 157:

Asn Glu Ser Ala Pro Arg Ser Pro Met Leu Pro Ser Ala Arg Pro Arg 1 5 10 15

Tyr Asp Ala He Ala Val Leu Leu Asn Glu Met His Ala Gly His Cys 20 25 30

Asp Phe Gly Leu Val Gly Pro Ala Pro Asp He Val Thr Asp Ala Ala 35 40 45

Gly Asp Asp Arg Ala Gly Leu Gly Val Asp Glu Gin Phe Arg His Val 50 55 60

Gly Phe Leu Glu Pro Ala Pro Val Leu Val Asp Gin Arg Asp Asp Leu 65 70 75 80

Gly Gly Leu Thr Val Asp Trp Lys Val Ser Trp Pro Arg Gin Arg Gly 85 90 95

Ala Thr Val Leu Ala Ala Val His Glu Trp Pro Pro He Val Val His 100 105 110

Phe Leu Val Ala Glu Leu Ser Gin Asp Arg Pro Gly Gin His Pro Phe 115 120 125

Asp Lys Asp Val Val Leu Gin Arg His Trp Leu Ala Leu Arg Arg Ser 130 135 140

Glu Thr Leu Glu His Thr Pro His Gly Arg Arg Pro Val Arg Pro Arg 145 150 155 160

His Arg Gly Asp Asp Arg Phe His Glu Arg Asp Pro Leu His Ser Val 165 170 175

Ala Met Leu Val Ser Pro Val Glu Ala Glu Arg Arg Ala Pro Val Val 180 185 190

Gin His Gin Tyr His Val Val Ala Glu Val Glu Arg He Pro Glu Arg 195 200 205

Glu Gin Lys Val Ser Leu Leu Ala He Ala He Ala Val Gly Ser Arg 210 215 220

Trp Ala Glu Leu Val Arg Arg Ala His Pro Asp Gin He Ala Gly His 225 230 235 240

Gin Pro Ala Gin Pro Phe Gin Val Arg His Asp Val Ala Pro Gin Val 245 250 255

Arg Arg Arg Gly Val Ala Val Leu Lys Asp Asp Gly Val Thr Leu Ala 260 265 270

Phe Val Asp He Arg His Ala Leu Pro Gly Asp Phe 275 280

(2) INFORMATION FOR SEQ ID NO: 158:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 264 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 158: ATGAACATGT CGTCGGTGGT GGGTCGCAAG GCCTTTGCGC GATTCGCCGG CTACTCCTCC 60

GCCATGCACG CGATCGCCGG TTTCTCCGAT GCGTTGCGCC AAGAGCTGCG GGGTAGCGGA 120

ATCGCCGTCT CGGTGATCCA CCCGGCGCTG ACCCAGACAC CGCTGTTGGC CAACGTCGAC 180

CCCGCCGACA TGCCGCCGCC GTTTCGCAGC CTCACGCCCA TTCCCGTTCA CTGGGTCGCG 240

GCAGCGGTGC TTGACGGTGT GGCG 264 (2) INFORMATION FOR SEQ ID NO: 159:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1171 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 159:

TAGTCGGCGA CGATGACGTC GCGGTCCAGG CCGACCGCTT CAAGCACCAG CGCGACCACG 60

AAGCCGGTGC GATCCTTACC CGCGAAGCAG TGGGTGAGCA CCGGGCGTCC GGCGGCAAGC 120

AGTGTGACGA CACGATGTAG CGCGCGCTGT GCTCCATTGC GCGTTGGGAA TTGGCGATAC 180

TCGTCGGTCA TGTAGCGGGT GGCCGCGTCA TTTATCGACT GGCTGGATTC GCCGGACTCG 240

CCGTTGGACC CGTCATTGGT TAGCAGCCTC TTGAATGCGG TTTCGTGCGG CGCTGAGTCG 300

TCGGCGTCAT CATCGGCGAG GTCGGGGAAC GGCAGCAGGT GGACGTCGAT GCCGTCCGGA 360

ACCCGTCCTG GACCGCGGCG GGCAACCTCC CGGGACGACC GCAGGTCGGC AACGTCGGTG 420

ATCCCCAGCC GGCGCAGCGT TGCCCCTCGT GCCGAATTCG GCACGAGGCT GGCGAGCCAC 480

CGGGCATCAC CAAGCAACGC TTGCCCAGTA CGGATCGTCA CTTCCGCATC CGGCAGACCA 540

ATCTCCTCGC CGCCCATCGT CAGATCCCGC TCGTGCGTTG ACAAGAACGG CCGCAGATGT 600

GCCAGCGGGT ATCGGAGATT GAACCGCGCA CGCAGTTCTT CAATCGCTGC GCGCTGCCGC 660

ACTATTGGCA CTTTCCGGCG GTCGCGGTAT TCAGCAAGCA TGCGAGTCTC GACGAACTCG 720

CCCCACGTAA CCCACGGCGT AGCTCCCGGC GTGACGCGGA GGATCGGCGG GTGATCTTTG 780

CCGCCACGCT CGTAGCCGTT GATCCACCGC TTCGCGGTGC CGGCGGGGAG GCCGATCAGC 840

TTATCGACCT CGGCGTATGC CGACGGCAAG CTGGGCGCGT TCGTCGAGGT CAAGAACTCC 900

ACCATCGGCA CCGGCACCAA GGTGCCGCAC CTGACCTACG TCGGCGACGC CGACATCGGC 960 GAGTACAGCA ACATCGGCGC CTCCAGCGTG TTCGTCAACT ACGACGGTAC GTCCAAACGG 1020

CGCACCACCG TCGGTTCGCA CGTACGGACC GGGTCCGACA CCATGTTCGT GGCCCCAGTA 1080

ACCATCGGCG ACGGCGCGTA TACCGGGGCC GGCACAGTGG TGCGGGAGGA TGTCCCGCCG 1140

GGGGCGCTGG CAGTGTCGGC GGGTCCGCAA C 1171 (2) INFORMATION FOR SEQ ID NO: 160:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 227 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 160:

GCAAAGGCGG CACCGGCGGG GCCGGCATGA ACAGCCTCGA CCCGCTGCTA GCCGCCCAAG 60

ACGGCGGCCA AGGCGGCACC GGCGGCACCG GCGGCAACGC CGGCGCCGGC GGCACCAGCT 120

TCACCCAAGG CGCCGACGGC AACGCCGGCA ACGGCGGTGA CGGCGGGGTC GGCGGCAACG 180

GCGGAAACGG CGGAAACGGC GCAGACAACA CCACCACCGC CGCCGCC 227 (2) INFORMATION FOR SEQ ID NO: 161:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 304 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 161:

CCTCGCCACC ATGGGCGGGC AGGGCGGTAG CGGTGGCGCC GGCTCTACCC CAGGCGCCAA 60

GGGCGCCCAC GGCTTCACTC CAACCAGCGG CGGCGACGGC GGCGACGGCG GCAACGGCGG 120

CAACTCCCAA GTGGTCGGCG GCAACGGCGG CGACGGCGGC AATGGCGGCA ACGGCGGCAG 180

CGCCGGCACG GGCGGCAACG GCGGCCGCGG CGGCGACGGC GCGTTTGGTG GCATGAGTGC 240

CAACGCCACC AACCCTGGTG AAAACGGGCC AAACGGTAAC CCCGGCGGCA ACGGTGGCGC 300 CGGC 304

(2) INFORMATION FOR SEQ ID NO: 162:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1439 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 162:

GTGGGACGCT GCCGAGGCTG TATAACAAGG ACAACATCGA CCAGCGCCGG CTCGGTGAGC 60

TGATCGACCT ATTTAACAGT GCGCGCTTCA GCCGGCAGGG CGAGCACCGC GCCCGGGATC 120

TGATGGGTGA GGTCTACGAA TACTTCCTCG GCAATTTCGC TCGCGCGGAA GGGAAGCGGG 180

GTGGCGAGTT CTTTACCCCG CCCAGCGTGG TCAAGGTGAT CGTGGAGGTG CTGGAGCCGT 240

CGAGTGGGCG GGTGTATGAC CCGTGCTGCG GTTCCGGAGG CATGTTTGTG CAGACCGAGA 300

AGTTCATCTA CGAACACGAC GGCGATCCGA AGGATGTCTC GATCTATGGC CAGGAAAGCA 360

TTGAGGAGAC CTGGCGGATG GCGAAGATGA ACCTCGCCAT CCACGGCATC GACAACAAGG 420

GGCTCGGCGC CCGATGGAGT GATACCTTCG CCCGCGACCA GCACCCGGAC GTGCAGATGG 480

ACTACGTGAT GGCCAATCCG CCGTTCAACA TCAAAGACTG GGCCCGCAAC GAGGAAGACC 540

CACGCTGGCG CTTCGGTGTT CCGCCCGCCA ATAACGCCAA CTACGCATGG ATTCAGCACA 600

TCCTGTACAA CTTGGCGCCG GGAGGTCGGG CGGGCGTGGT GATGGCCAAC GGGTCGATGT 660

CGTCGAACTC CAACGGCAAG GGGGATATTC GCGCGCAAAT CGTGGAGGCG GATTTGGTTT 720

CCTGCATGGT CGCGTTACCC ACCCAGCTGT TCCGCAGCAC CGGAATCCCG GTGTGCCTGT 780

GGTTTTTCGC CAAAAACAAG GCGGCAGGTA AGCAAGGGTC TATCAACCGG TGCGGGCAGG 840

TGCTGTTCAT CGACGCTCGT GAACTGGGCG ACCTAGTGGA CCCCGCCGAG CGGGCGCTGA 900

CCAACGAGGA GATCGTCCGC ATCGGGGATA CCTTCCACGC GAGCACGACC ACCGGCAACG 960

CCGGCTCCGG TGGTGCCGGC GGTAATGGGG GCACTGGCCT CAACGGCGCG GGCGGTGCTG 1020

GCGGGGCCGG CGGCAACGCG GGTGTCGCCG GCGTGTCCTT CGGCAACGCT GTGGGCGGCG 1080

ACGGCGGCAA CGGCGGCAAC GGCGGCCACG GCGGCGACGG CACGACGGGC GGCGCCGGCG 1140

GCAAGGGCGG CAACGGCAGC AGCGGTGCCG CCAGCGGCTC AGGCGTCGTC AACGTCACCG 1200 CCGGCCACGG CGGCAACGGC GGCAATGGCG GCAACGGCGG CAACGGCTCC GCGGGCGCCG 1260

GCGGCCAGGG CGGTGCCGGC GGCAGCGCCG GCAACGGCGG CCACGGCGGC GGTGCCACCG 1320

GCGGCGCCAG CGGCAAGGGC GGCAACGGCA CCAGCGGTGC CGCCAGCGGC TCAGGCGTCA 1380

TCAACGTCAC CGCCGGCCAC GGCGGCAACG GCGGCAATGG CCGCAACGGC GGCAACGGC 1439 (2) INFORMATION FOR SEQ ID NO: 163:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 329 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 163:

GGGCCGGCGG GGCCGGATTT TCTCGTGCCT TGATTGTCGC TGGGGATAAC GGCGGTGATG 60

GTGGTAACGG CGGGATGGGC GGGGCTGGCG GGGCTGGCGG CCCCGGCGGG GCCGGCGGCC 120

TGATCAGCCT GCTGGGCGGC CAAGGCGCCG GCGGGGCCGG CGGGACCGGC GGGGCCGGCG 180

GTGTTGGCGG TGACGGCGGG GCCGGCGGCC CCGGCAACCA GGCCTTCAAC GCAGGTGCCG 240

GCGGGGCCGG CGGCCTGATC AGCCTGCTGG GCGGCCAAGG CGCCGGCGGG GCCGGCGGGA 300

CCGGCGGGGC CGGCGGTGTT GGCGGTGAC 329 (2) INFORMATION FOR SEQ ID NO: 164:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 80 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 164:

GCAACGGTGG CAACGGCGGC ACCAGCACGA CCGTGGGGAT GGCCGGAGGT AACTGTGGTG 60

CCGCCGGGCT GATCGGCAAC 80 (2) INFORMATION FOR SEQ ID NO: 165: (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 392 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 165:

GGGCTGTGTC GCACTCACAC CGCCGCATTC GGCGACGTTG GCCGCCCAAT ATCCAGCTCA 60

AGGCCTACTA CTTACCGTCG GAGGACCGCC GCATCAAGGT GCGGGTCAGC GCCCAAGGAA 120

TCAAGGTCAT CGACCGCGAC GGGCATCGAG GCCGTCGTCG CGCGGCTCGG GCAGGATCCG 180

CCCCGGCGCA CTTCGCGCGC CAAGCGGGCT CATCGCTCCG AACGGCGGCG ATCCTGTGAG 240

CACAACTGAT GGCGCGCAAC GAGATTCGTC CAATTGTCAA GCCGTGTTCG ACCGCAGGGA 300

CCGGTTATAC GTATGTCAAC CTATGTCACT CGCAAGAACC GGCATAACGA TCCCGTGATC 360

CGCCGACAGC CCACGAGTGC AAGACCGTTA CA 392 (2) INFORMATION FOR SEQ ID NO: 166:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 535 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 166:

ACCGGCGCCA CCGGCGGCAC CGGGTTCGCC GGTGGCGCCG GCGGGGCCGG CGGGCAGGGC 60

GGTATCAGCG GTGCCGGCGG CACCAACGGC TCTGGTGGCG CTGGCGGCAC CGGCGGACAA 120

GGCGGCGCCG GGGGCGCTGG CGGGGCCGGC GCCGATAACC CCACCGGCAT CGGCGGCGCC 180

GGCGGCACCG GCGGCACCGG CGGAGCGGCC GGAGCCGGCG GGGCCGGTGG CGCCATCGGT 240

ACCGGCGGCA CCGGCGGCGC GGTGGGCAGC GTCGGTAACG CCGGGATCGG CGGTACCGGC 300

GGTACGGGTG GTGTCGGTGG TGCTGGTGGT GCAGGTGCGG CTGCGGCCGC TGGCAGCAGC 360

GCTACCGGTG GCGCCGGGTT CGCCGGCGGC GCCGGCGGAG AAGGCGGACC GGGCGGCAAC 420

AGCGGTGTGG GCGGCACCAA CGGCTCCGGC GGCGCCGGCG GTGCAGGCGG CAAGGGCGGC 480 ACCGGAGGTG CCGGCGGGTC CGGCGCGGAC AACCCCACCG GTGCTGGTTT CGCCG 535

(2) INFORMATION FOR SEQ ID NO: 167:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 690 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 167:

CCGACGTCGC CGGGGCGATA CGGGGGTCAC CGACTACTAC ATCATCCGCA CCGAGAATCG 60

GCCGCTGCTG CAACCGCTGC GGGCGGTGCC GGTCATCGGA GATCCGCTGG CCGACCTGAT 120

CCAGCCGAAC CTGAAGGTGA TCGTCAACCT GGGCTACGGC GACCCGAACT ACGGCTACTC 180

GACGAGCTAC GCCGATGTGC GAACGCCGTT CGGGCTGTGG CCGAACGTGC CGCCTCAGGT 240

CATCGCCGAT GCCCTGGCCG CCGGAACACA AGAAGGCATC CTTGACTTCA CGGCCGACCT 300

GCAGGCGCTG TCCGCGCAAC CGCTCACGCT CCCGCAGATC CAGCTGCCGC AACCCGCCGA 360

TCTGGTGGCC GCGGTGGCCG CCGCACCGAC GCCGGCCGAG GTGGTGAACA CGCTCGCCAG 420

GATCATCTCA ACCAACTACG CCGTCCTGCT GCCCACCGTG GACATCGCCC TCGCCTGGTC 480

ACCACCCTGC CGCTGTACAC CACCCAACTG TTCGTCAGGC AACTCGCTGC GGGCAATCTG 540

ATCAACGCGA TCGGCTATCC CCTGGCGGCC ACCGTAGGTT TAGGCACGAT CGATAGCGGG 600

CGGCGTGGAA TTGCTCACCC TCCTCGCGGC GGCCTCGGAC ACCGTTCGAA ACATCGAGGG 660

CCTCGTCACC TAACGGATTC CCGACGGCAT 690 (2) INFORMATION FOR SEQ ID NO: 168:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 407 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 168: ACGGTGACGG CGGTACTGGC GGCGGCCACG GCGGCAACGG CGGGAATCCC GGGTGGCTCT 60

TGGGCACAGC CGGGGGTGGC GGCAACGGTG GCGCCGGCAG CACCGGTACT GCAGGTGGCG 120

GCTCTGGGGG CACCGGCGGC GACGGCGGGA CCGGCGGGCG TGGCGGCCTG TTAATGGGCG 180

CCGGCGCCGG CGGGCACGGT GGCACTGGCG GCGCGGGCGG TGCCGGTGTC GACGGTGGCG 240

GCGCCGGCGG GGCCGGCGGG GCCGGCGGCA ACGGCGGCGC CGGGGGTCAA GCCGCCCTGC 300

TGTTCGGGCG CGGCGGCACC GGCGGAGCCG GCGGCTACGG CGGCGATGGC GGTGGCGGCG 360

GTGACGGCTT CGACGGCACG ATGGCCGGCC TGGGTGGTAC CGGTGGC 407 (2) INFORMATION FOR SEQ ID NO: 169:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 468 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 169:

GATCGGTCAG CGCATCGCCC TCGGCGGCAA GCGATTCCGC GGTCTCACCG AAGAACATCG 60

TGCACGCGGC GGCGCGGACC AGCCCGCTGC GCTGCGGCGC GTCGAACGCC TCCAGCAGGC 120

ACACCCAGTC CTTGGCGGCC TGCGAGGCGA ACACGTCGGT GTCACCGGTG TAGATCGCCG 180

GGATGCCCGC CTCCGCCAAC GCATTCCGGC ACGCCCGCGC GTCTTTGTGA TGCTCGACGA 240

TCACCGCGAT GTCTGCGGCC ACCACGGGCC GCCCGGCGAA GGTGGCCCCG CTGGCCAGTA 300

GCGCCGCGAC GTCGGCGGCC AGGTCGTCGG GGATGTGCCG GCGCAGCGCT CCGGCGCGAC 360

GCCCGAAAAA CGACCCCTCA CCCAGCTGGG TCCCGCTGGC ATATCCCTTG CCGTCCTGGG 420

CGATATTGGA CGCGCATGCC CCGACCGCGT ACAGGCCGGC CACCACCG 468 (2) INFORMATION FOR SEQ ID NO: 170:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 219 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 170:

GGTGGTAACG GCGGCCAGGG TGGCATCGGC GGCGCCGGCG AGAGAGGCGC CGACGGCGCC 60

GGCCCCAATG CTAACGGCGC AAACGGCGAG AACGGCGGTA GCGGTGGTAA CGGTGGCGAC 120

GGCGGCGCCG GCGGCAATGG CGGCGCGGGC GGCAACGCGC AGGCGGCCGG GTACACCGAC 180

GGCGCCACGG GCACCGGCGG CGACGGCGGC AACGGCGGC 219 (2) INFORMATION FOR SEQ ID NO: 171:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 494 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 171:

TAGCTCCGGC GAGGGCGGCA ACGGCGGCGA CGGTGGCCAC GGCGGTGACG GCGTCGGCGG 60

CAACAGTTCC GTCACCCAAG GCGGCAGCGG CGGTGGCGGC GGCGCCGGCG GCGCCGGCGG 120

CAGCGGCTTT TTCGGCGGCA AGGGCGGCTT CGGCGGCGAC GGCGGTCAGG GCGGCCCCAA 180

CGGCGGCGGT ACCGTCGGCA CCGTGGCCGG TGGCGGCGGC AACGGCGGTG TCGGCGGCCG 240

GGGCGGCGAC GGCGTCTTTG CCGGTGCCGG CGGCCAGGGC GGCCTCGGTG GGCAGGGCGG 300

CAATGGCGGC GGCTCCACCG GCGGCAACGG CGGCCTTGGC GGCGCGGGCG GTGGCGGAGG 360

CAACGCCCCG GCTCGTGCCG AATCCGGGCT GACCATGGAC AGCGCGGCCA AGTTCGCTGC 420

CATCGCATCA GGCGCGTACT GCCCCGAACA CCTGGAACAT CACCCGAGTT AGCGGGGCGC 480

ATTTCCTGAT CACC 494 (2) INFORMATION FOR SEQ ID NO: 172:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 220 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 172:

GGGCCGGTGG TGCCGCGGGC CAGCTCTTCA GCGCCGGAGG CGCGGCGGGT GCCGTTGGGG 60

TTGGCGGCAC CGGCGGCCAG GGTGGGGCTG GCGGTGCCGG AGCGGCCGGC GCCGACGCCC 120

CCGCCAGCAC AGGTCTAACC GGTGGTACCG GGTTCGCTGG CGGGGCCGGC GGCGTCGGCG 180

GCCAGAGCGG CAACGCCATT GCCGGCGGCA TCAACGGCTC 220 (2) INFORMATION FOR SEQ ID NO: 173:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 388 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 173:

ATGGCGGCAA CGGGGGCCCC GGCGGTGCTG GCGGGGCCGG CGACTACAAT TTCCAACGGC 60

GGGCAGGGTG GTGCCGGCGG CCAAGGCGGC CAAGGCGGCC TGGGCGGGGC AAGCACCACC 120

TGATCGGCCT AGCCGCACCC GGGAAAGCCG ATCCAACAGG CGACGATGCC GCCTTCCTTG 180

CCGCGTTGGA CCAGGCCGGC ATCACCTACG CTGACCCAGG CCACGCCATA ACGGCCGCCA 240

AGGCGATGTG TGGGCTGTGT GCTAACGGCG TAACAGGTCT ACAGCTGGTC GCGGACCTGC 300

GGGACTACAA TCCCGGGCTG ACCATGGACA GCGCGGCCAA GTTCGCTGCC ATCGCATCAG 360

GCGCGTACTG CCCCGAACAC CTGGAACA 388 (2) INFORMATION FOR SEQ ID NO: 174:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 400 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 174: GCAAAGGCGG CACCGGCGGG GCCGGCATGA ACAGCCTCGA CCCGCTGCTA GCCGCCCAAG 60 ACGGCGGCCA AGGCGGCACC GGCGGCACCG GCGGCAACGC CGGCGCCGGC GGCACCAGCT 120 TCACCCAAGG CGCCGACGGC AACGCCGGCA ACGGCGGTGA CGGCGGGGTC GGCGGCAACG 180

GCGGAAACGG CGGAAACGGC GCAGACAACA CCACCACCGC CGCCGCCGGC ACCACAGGCG 240

GCGACGGCGG GGCCGGCGGG GCCGGCGGAA CCGGCGGAAC CGGCGGAGCC GCCGGCACCG 300

GCACCGGCGG CCAACAAGGC AACGGCGGCA ACGGCGGCAC CGGCGGCAAA GGCGGCACCG 360

GCGGCGACGG TGCACTCTCA GGCAGCACCG GTGGTGCCGG 400 (2) INFORMATION FOR SEQ ID NO: 175:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 538 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 175:

GGCAACGGCG GCAACGGCGG CATCGCCGGC ATTGGGCGGC AACGGCGTTC CGGGACGGGC 60

AGCGGCAACG GCGGCCAACG GCGGCAGCGG CGGCAACGGC GGCAACGCCG GCATGGGCGG 120

CAACAGCGGC ACCGGCAGCG GCGACGGCGG TGCCGGCGGG AACGGCGGCG CGGCGGGCAC 180

GGGCGGCACC GGCGGCGACG GCGGCCTCAC CGGTACTGGC GGCACCGGCG GCAGCGGTGG 240

CACCGGCGGT GACGGCGGTA ACGGCGGCAA CGGAGCAGAT AACACCGCAA ACATGACTGC 300

GCAGGCGGGC GGTGACGGTG GCAACGGCGG CGACGGTGGC TTCGGCGGCG GGGCCGGGGC 360

CGGCGGCGGT GGCTTGACCG CTGGCGCCAA CGGCACCGGC GGGCAAGGCG GCGCCGGCGG 420

CGATGGCGGC AACGGGGCCA TCGGCGGCCA CGGCCCACTC ACTGACGACC CCGGCGGCAA 480

CGGGGGCACC GGCGGCAACG GCGGCACCGG CGGCACCGGC GGCGCGGGCA TCGGCAGC 538 (2) INFORMATION FOR SEQ ID NO: 176:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 239 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 176:

GGGCCGGTGG TGCCGCGGGC CAGCTCTTCA GCGCCGGAGG CGCGGCGGGT GCCGTTGGGG 60

TTGGCGGCAC CGGCGGCCAG GGTGGGGCTG GCGGTGCCGG AGCGGCCGGC GCCGACGCCC 120

CCGCCAGCAC AGGTCTAACC GGTGGTACCG GGTTCGCTGG CGGGGCCGGC GGCGTCGGCG 180

GCCACGGCGG CAACGCCATT GCCGGCGGCA TCAACGGCTC CGGTGGTGCC GGCGGCACC 239 (2) INFORMATION FOR SEQ ID NO: 177:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 985 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 177:

AGCAGCGCTA CCGGTGGCGC CGGGTTCGCC GGCGGCGCCG GCGGAGAAGG CGGAGCGGGC 60

GGCAACAGCG GTGTGGGCGG CACCAACGGC TCCGGCGGCG CCGGCGGTGC AGGCGGCAAG 120

GGCGGCACCG GAGGTGCCGG CGGGTCCGGC GCGGACAACC CCACCGGTGC TGGTTTCGCC 180

GGTGGCGCCG GCGGCACAGG TGGCGCGGCC GGCGCCGGCG GGGCCGGCGG GGCGACCGGT 240

ACCGGCGGCA CCGGCGGCGT TGTCGGCGCC ACCGGTAGTG CAGGCATCGG CGGGGCCGGC 300

GGCCGCGGCG GTGACGGCGG CGATGGGGCC AGCGGTCTCG GCCTGGGCCT CTCCGGCTTT 360

GACGGCGGCC AAGGCGGCCA AGGCGGGGCC GGCGGCAGCG CCGGCGCCGG CGGCATCAAC 420

GGGGCCGGCG GGGCCGGCGG CAACGGCGGC GACGGCGGGG ACGGCGCAAC CGGTGCCGCA 480

GGTCTCGGCG ACAACGGCGG GGTCGGCGGT GACGGTGGGG CCGGTGGCGC CGCCGGCAAC 540

GGCGGCAACG CGGGCGTCGG CCTGACAGCC AAGGCCGGCG ACGGCGGCGC CGCGGGCAAT 600

GGCGGCAACG GGGGCGCCGG CGGTGCTGGC GGGGCCGGCG ACAACAATTT CAACGGCGGC 660

CAGGGTGGTG CCGGCGGCCA AGGCGGCCAA GGCGGCTTGG GCGGGGCAAG CACCACCTGA 720

TCGGCCTAGC CGCACCCGGG AAAGCCGATC CAACAGGCGA CGATGCCGCC TTCCTTGCCG 780

CGTTGGACCA GGCCGGCATC ACCTACGCTG ACCCAGGCCA CGCCATAACG GCCGCCAAGG 840

CGATGTGTGG GCTGTGTGCT AACGGCGTAA CAGGTCTACA GCTGGTCGCG GACCTGCGGG 900

AATACAATCC CGGGCTGACC ATGGACAGCG CGGCCAAGTT CGCTGCCATC GCATCAGGCG 960 CGTACTGCCC CGAACACCTG GAACA 985

(2) INFORMATION FOR SEQ ID NO: 178:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 2138 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 178:

CGGCACGAGG ATCGGTACCC CGCGGCATCG GCAGCTGCCG ATTCGCCGGG TTTCCCCACC 60

CGAGGAAAGC CGCTACCAGA TGGCGCTGCC GAAGTAGGGC GATCCGTTCG CGATGCCGGC 120

ATGAACGGGC GGCATCAAAT TAGTGCAGGA ACCTTTCAGT TTAGCGACGA TAATGGCTAT 180

AGCACTAAGG AGGATGATCC GATATGACGC AGTCGCAGAC CGTGACGGTG GATCAGCAAG 240

AGATTTTGAA CAGGGCCAAC GAGGTGGAGG CCCCGATGGC GGACCCACCG ACTGATGTCC 300

CCATCACACC GTGCGAACTC ACGGCGGCTA AAAACGCCGC CCAACAGCTG GTATTGTCCG 360

CCGACAACAT GCGGGAATAC CTGGCGGCCG GTGCCAAAGA GCGGCAGCGT CTGGCGACCT 420

CGCTGCGCAA CGCGGCCAAG GCGTATGGCG AGGTTGATGA GGAGGCTGCG ACCGCGCTGG 480

ACAACGACGG CGAAGGAACT GTGCAGGCAG AATCGGCCGG GGCCGTCGGA GGGGACAGTT 540

CGGCCGAACT AACCGATACG CCGAGGGTGG CCACGGCCGG TGAACCCAAC TTCATGGATC 600

TCAAAGAAGC GGCAAGGAAG CTCGAAACGG GCGACCAAGG CGCATCGCTC GCGCACTTTG 660

CGGATGGGTG GAACACTTTC AACCTGACGC TGCAAGGCGA CGTCAAGCGG TTCCGGGGGT 720

TTGACAACTG GGAAGGCGAT GCGGCTACCG CTTGCGAGGC TTCGCTCGAT CAACAACGGC 780

AATGGATACT CCACATGGCC AAATTGAGCG CTGCGATGGC CAAGCAGGCT CAATATGTCG 840

CGCAGCTGCA CGTGTGGGCT AGGCGGGAAC ATCCGACTTA TGAAGACATA GTCGGGCTCG 900

AACGGCTTTA CGCGGAAAAC CCTTCGGCCC GCGACCAAAT TCTCCCGGTG TACGCGGAGT 960

ATCAGCAGAG GTCGGAGAAG GTGCTGACCG AATACAACAA CAAGGCAGCC CTGGAACCGG 1020

TAAACCCGCC GAAGCCTCCC CCCGCCATCA AGATCGACCC GCCCCCGCCT CCGCAAGAGC 1080

AGGGATTGAT CCCTGGCTTC CTGATGCCGC CGTCTGACGG CTCCGGTGTG ACTCCCGGTA 1140 CCGGGATGCC AGCCGCACCG ATGGTTCCGC CTACCGGATC GCCGGGTGGT GGCCTCCCGG 1200

CTGACACGGC GGCGCAGCTG ACGTCGGCTG GGCGGGAAGC CGCAGCGCTG TCGGGCGACC 1260

TGGCGGTCAA AGCGGCATCG CTCGGTGGCG GTGGAGGCGG CGGGGTGCCG TCGGCGCCGT 1320

TGGGATCCGC GATCGGGGGC GCCGAATCGG TGCGGCCCGC TGGCGCTGGT GACATTGCCG 1380

GCTTAGGCCA GGGAAGGGCC GGCGGCGGCG CCGCGCTGGG CGGCGGTGGC ATGGGAATGC 1440

CGATGGGTGC CGCGCATCAG GGACAAGGGG GCGCCAAGTC CAAGGGTTCT CAGCAGGAAG 1500

ACGAGGCGCT CTACACCGAG GATCGGGCAT GGACCGAGGC CGTCATTGGT AACCGTCGGC 1560

GCCAGGACAG TAAGGAGTCG AAGTGAGCAT GGACGAATTG GACCCGCATG TCGCCCGGGC 1620

GTTGACGCTG GCGGCGCGGT TTCAGTCGGC CCTAGACGGG ACGCTCAATC AGATGAACAA 1680

CGGATCCTTC CGCGCCACCG ACGAAGCCGA GACCGTCGAA GTGACGATCA ATGGGCACCA 1740

GTGGCTCACC GGCCTGCGCA TCGAAGATGG TTTGCTGAAG AAGCTGGGTG CCGAGGCGGT 1800

GGCTCAGCGG GTCAACGAGG CGCTGCACAA TGCGCAGGCC GCGGCGTCCG CGTATAACGA 1860

CGCGGCGGGC GAGCAGCTGA CCGCTGCGTT ATCGGCCATG TCCCGCGCGA TGAACGAAGG 1920

AATGGCCTAA GCCCATTGTT GCGGTGGTAG CGACTACGCA CCGAATGAGC GCCGCAATGC 1980

GGTCATTCAG CGCGCCCGAC ACGGCGTGAG TACGCATTGT CAATGTTTTG ACATGGATCG 2040

GCCGGGTTCG GAGGGCGCCA TAGTCCTGGT CGCCAATATT GCCGCAGCTA GCTGGTCTTA 2100

GGTTCGGTTA CGCTGGTTAA TTATGACGTC CGTTACCA 2138 (2) INFORMATION FOR SEQ ID NO: 179:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 460 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 179:

Met Thr Gin Ser Gin Thr Val Thr Val Asp Gin Gin Glu He Leu Asn

1 5 10 15

Arg Ala Asn Glu Val Glu Ala Pro Met Ala Asp Pro Pro Thr Asp Val 20 25 30

Pro He Thr Pro Cys Glu Leu Thr Ala Ala Lys Asn Ala Ala Gin Gin 35 40 45

Leu Val Leu Ser Ala Asp Asn Met Arg Glu Tyr Leu Ala Ala Gly Ala 50 55 60

Lys Glu Arg Gin Arg Leu Ala Thr Ser Leu Arg Asn Ala Ala Lys Ala 65 70 75 80

Tyr Gly Glu Val Asp Glu Glu Ala Ala Thr Ala Leu Asp Asn Asp Gly 85 90 95

Glu Gly Thr Val Gin Ala Glu Ser Ala Gly Ala Val Gly Gly Asp Ser 100 105 110

Ser Ala Glu Leu Thr Asp Thr Pro Arg Val Ala Thr Ala Gly Glu Pro 115 120 125

Asn Phe Met Asp Leu Lys Glu Ala Ala Arg Lys Leu Glu Thr Gly Asp 130 135 140

Gin Gly Ala Ser Leu Ala His Phe Ala Asp Gly Trp Asn Thr Phe Asn 145 150 155 160

Leu Thr Leu Gin Gly Asp Val Lys Arg Phe Arg Gly Phe Asp Asn Trp 165 170 175

Glu Gly Asp Ala Ala Thr Ala Cys Glu Ala Ser Leu Asp Gin Gin Arg 180 185 190

Gin Trp He Leu His Met Ala Lys Leu Ser Ala Ala Met Ala Lys Gin 195 200 205

Ala Gin Tyr Val Ala Gin Leu His Val Trp Ala Arg Arg Glu His Pro 210 215 220

Thr Tyr Glu Asp He Val Gly Leu Glu Arg Leu Tyr Ala Glu Asn Pro 225 230 235 240

Ser Ala Arg Asp Gin He Leu Pro Val Tyr Ala Glu Tyr Gin Gin Arg 245 250 255

Ser Glu Lys Val Leu Thr Glu Tyr Asn Asn Lys Ala Ala Leu Glu Pro 260 265 270

Val Asn Pro Pro Lys Pro Pro Pro Ala He Lys He Asp Pro Pro Pro 275 280 285

Pro Pro Gin Glu Gin Gly Leu He Pro Gly Phe Leu Met Pro Pro Ser 290 295 300

Asp Gly Ser Gly Val Thr Pro Gly Thr Gly Met Pro Ala Ala Pro Met 305 310 315 320

Val Pro Pro Thr Gly Ser Pro Gly Gly Gly Leu Pro Ala Asp Thr Ala 325 330 335 Ala Gin Leu Thr Ser Ala Gly Arg Glu Ala Ala Ala Leu Ser Gly Asp 340 345 350

Val Ala Val Lys Ala Ala Ser Leu Gly Gly Gly Gly Gly Gly Gly Val 355 360 365

Pro Ser Ala Pro Leu Gly Ser Ala He Gly Gly Ala Glu Ser Val Arg 370 375 380

Pro Ala Gly Ala Gly Asp He Ala Gly Leu Gly Gin Gly Arg Ala Gly 385 390 395 400

Gly Gly Ala Ala Leu Gly Gly Gly Gly Met Gly Met Pro Met Gly Ala 405 410 415

Ala His Gin Gly Gin Gly Gly Ala Lys Ser Lys Gly Ser Gin Gin Glu 420 425 430

Asp Glu Ala Leu Tyr Thr Glu Asp Arg Ala Trp Thr Glu Ala Val He 435 440 445

Gly Asn Arg Arg Arg Gin Asp Ser Lys Glu Ser Lys 450 455 460

(2) INFORMATION FOR SEQ ID NO: 180:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 277 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 180:

Ala Gly Asn Val Thr Ser Ala Ser Gly Pro His Arg Phe Gly Ala Pro 1 5 10 15

Asp Arg Gly Ser Gin Arg Arg Arg Arg His Pro Ala Ala Ser Thr Ala 20 25 30

Thr Glu Arg Cys Arg Phe Asp Arg His Val Ala Arg Gin Arg Cys Gly 35 40 45

Phe Pro Pro Ser Arg Arg Gin Leu Arg Arg Arg Val Ser Arg Glu Ala 50 55 60

Thr Thr Arg Arg Ser Gly Arg Arg Asn His Arg Cys Gly Trp His Pro 65 70 75 80

Gly Thr Gly Ser His Thr Gly Ala Val Arg Arg Arg His Gin Glu Ala 85 90 95

Arg Asp Gin Ser Leu Leu Leu Arg Arg Arg Gly Arg Val Asp Leu Asp 100 105 110

Gly Gly Gly Arg Leu Arg Arg Val Tyr Arg Phe Gin Gly Cys Leu Val 115 120 125

Val Val Phe Gly Gin His Leu Leu Arg Pro Leu Leu He Leu Arg Val 130 135 140

His Arg Glu Asn Leu Val Ala Gly Arg Arg Val Phe Arg Val Lys Pro 145 150 155 160

Phe Glu Pro Asp Tyr Val Phe He Ser Arg Met Phe Pro Pro Ser Pro 165 170 175

His Val Gin Leu Arg Asp He Leu Ser Leu Leu Gly His Arg Ser Ala 180 185 190

Gin Phe Gly His Val Glu Tyr Pro Leu Pro Leu Leu He Glu Arg Ser 195 200 205

Leu Ala Ser Gly Ser Arg He Ala Phe Pro Val Val Lys Pro Pro Glu 210 215 220

Pro Leu Asp Val Ala Leu Gin Arg Gin Val Glu Ser Val Pro Pro He 225 230 235 240

Arg Lys Val Arg Glu Arg Cys Ala Leu Val Ala Arg Phe Glu Leu Pro 245 250 255

Cys Arg Phe Phe Glu He His Glu Val Gly Phe Thr Gly Arg Gly His 260 265 270

Pro Arg Arg He Gly 275

(2) INFORMATION FOR SEQ ID NO: 181:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 192 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS:

( D ) TOPOLOGY : linear

( xi ) SEQUENCE DESCRI PTION : SEQ I D NO : 181 :

Arg Val Ala Ala Ser Phe He Asp Trp Leu Asp Ser Pro Asp Ser Pro 1 5 10 15 Leu Asp Pro Ser Leu Val Ser Ser Leu Leu Asn Ala Val Ser Cys Gly 20 25 30

Ala Glu Ser Ser Ala Ser Ser Ser Ala Arg Ser Gly Asn Gly Ser Arg 35 40 45

Trp Thr Ser Met Pro Ser Gly Thr Arg Pro Gly Pro Arg Arg Ala Thr 50 55 60

Ser Arg Asp Asp Arg Arg Ser Ala Thr Ser Val He Pro Ser Arg Arg 65 70 75 80

Ser Val Ala Pro Arg Ala Glu Phe Gly Thr Arg Leu Ala Ser His Arg 85 90 95

Ala Ser Pro Ser Asn Ala Cys Pro Val Arg He Val Thr Ser Ala Ser 100 105 110

Gly Arg Pro He Ser Ser Pro Pro He Val Arg Ser Arg Ser Cys Val 115 120 125

Asp Lys Asn Gly Arg Arg Cys Ala Ser Gly Tyr Arg Arg Leu Asn Arg 130 135 140

Ala Arg Ser Ser Ser He Ala Ala Arg Cys Arg Thr He Gly Thr Phe 145 150 155 160

Arg Arg Ser Arg Tyr Ser Ala Ser Met Arg Val Ser Thr Asn Ser Pro 165 170 175

His Val Thr His Gly Val Ala Pro Gly Val Thr Arg Arg He Gly Gly 180 185 190

(2) INFORMATION FOR SEQ ID NO: 182:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 196 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 182:

Gin Glu Arg Pro Gin Met Cys Gin Arg Val Ser Glu He Glu Pro Arg

1 5 10 15

Thr Gin Phe Phe Asn Arg Cys Ala Leu Pro His Tyr Trp His Phe Pro 20 25 30

Ala Val Ala Val Phe Ser Lys His Ala Ser Leu Asp Glu Leu Ala Pro 35 40 45

Arg Asn Pro Arg Arg Ser Ser Arg Arg Asp Ala Glu Asp Arg Arg Val 50 55 60

He Phe Ala Ala Thr Leu Val Ala Val Asp Pro Pro Leu Arg Gly Ala 65 70 75 80

Gly Gly Glu Ala Asp Gin Leu He Asp Leu Gly Val Cys Arg Arg Gin 85 90 95

Ala Gly Arg Val Arg Arg Gly Gin Glu Leu His His Arg His Arg His 100 105 110

Gin Gly Ala Ala Pro Asp Leu Arg Arg Arg Arg Arg His Arg Arg Val 115 120 125

Gin Gin His Arg Arg Leu Gin Arg Val Arg Gin Leu Arg Arg Tyr Val 130 135 140

Gin Thr Ala His His Arg Arg Phe Ala Arg Thr Asp Arg Val Arg His 145 150 155 160

His Val Arg Gly Pro Ser Asn His Arg Arg Arg Arg Val Tyr Arg Gly 165 170 175

Arg His Ser Gly Ala Gly Gly Cys Pro Ala Gly Gly Ala Gly Ser Val 180 185 190

Gly Gly Ser Ala 195

(2) INFORMATION FOR SEQ ID NO:183:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 311 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:183:

Val Arg Cys Gly Thr Leu Val Pro Val Pro Met Val Glu Phe Leu Thr 1 5 10 15

Ser Thr Asn Ala Pro Ser Leu Pro Ser Ala Tyr Ala Glu Val Asp Lys 20 25 30

Leu He Gly Leu Pro Ala Gly Thr Ala Lys Arg Trp He Asn Gly Tyr 35 40 45 Glu Arg Gly Gly Lys Asp His Pro Pro He Leu Arg Val Thr Pro Gly 50 55 60

Ala Thr Pro Trp Val Thr Trp Gly Glu Phe Val Glu Thr Arg Met Leu 65 70 75 80

Ala Glu Tyr Arg Asp Arg Arg Lys Val Pro He Val Arg Gin Arg Ala 85 90 95

Ala He Glu Glu Leu Arg Ala Arg Phe Asn Leu Arg Tyr Pro Leu Ala 100 105 110

His Leu Arg Pro Phe Leu Ser Thr His Glu Arg Asp Leu Thr Met Gly 115 120 125

Gly Glu Glu He Gly Leu Pro Asp Ala Glu Val Thr He Arg Thr Gly 130 135 140

Gin Ala Leu Leu Gly Asp Ala Arg Trp Leu Ala Ser Leu Val Pro Asn 145 150 155 160

Ser Ala Arg Gly Ala Thr Leu Arg Arg Leu Gly He Thr Asp Val Ala 165 170 175

Asp Leu Arg Ser Ser Arg Glu Val Ala Arg Arg Gly Pro Gly Arg Val 180 185 190

Pro Asp Gly He Asp Val His Leu Leu Pro Phe Pro Asp Leu Ala Asp 195 200 205

Asp Asp Ala Asp Asp Ser Ala Pro His Glu Thr Ala Phe Lys Arg Leu 210 215 220

Leu Thr Asn Asp Gly Ser Asn Gly Glu Ser Gly Glu Ser Ser Gin Ser 225 230 235 240

He Asn Asp Ala Ala Thr Arg Tyr Met Thr Asp Glu Tyr Arg Gin Phe 245 250 255

Pro Thr Arg Asn Gly Ala Gin Arg Ala Leu His Arg Val Val Thr Leu 260 265 270

Leu Ala Ala Gly Arg Pro Val Leu Thr His Cys Phe Ala Gly Lys Asp 275 280 285

Arg Thr Gly Phe Val Val Ala Leu Val Leu Glu Ala Val Gly Leu Asp 290 295 300

Arg Asp Val He Val Ala Asp 305, 310

(2) INFORMATION FOR SEQ ID NO: 184:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 2072 base pairs (B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 184:

CTCGTGCCGA TTCGGCACGA GCTGAGCAGC CCAAGGGGCC GTTCGGCGAA GTCATCGAGG 60

CATTCGCCGA CGGGCTGGCC GGCAAGGGTA AGCAAATCAA CACCACGCTG AACAGCCTGT 120

CGCAGGCGTT GAACGCCTTG AATGAGGGCC GCGGCGACTT CTTCGCGGTG GTACGCAGCC 180

TGGCGCTATT CGTCAACGCG CTACATCAGG ACGACCAACA GTTCGTCGCG TTGAACAAGA 240

ACCTTGCGGA GTTCACCGAC AGGTTGACCC ACTCCGATGC GGACCTGTCG AACGCCATCC 300

AGCAATTCGA CAGCTTGCTC GCCGTCGCGC GCCCGTTCTT CGCCAAGAAC CGCGAGGTGC 360

TGACGCATGA CGTCAATAAT CTCGCGACCG TGACCACCAC GTTGCTGCAG CCCGATCCGT 420

TGGATGGGTT GGAGACCGTC CTGCACATCT TCCCGACGCT GGCGGCGAAC ATTAACCAGC 480

TTTACCATCC GACACACGGT GGCGTGGTGT CGCTTTCCGC GTTCACGAAT TTCGCCAACC 540

CGATGGAGTT CATCTGCAGC TCGATTCAGG CGGGTAGCCG GCTCGGTTAT CAAGAGTCGG 600

CCGAACTCTG TGCGCAGTAT CTGGCGCCAG TCCTCGATGC GATCAAGTTC AACTACTTTC 660

CGTTCGGCCT GAACGTGGCC AGCACCGCCT CGACACTGCC TAAAGAGATC GCGTACTCCG 720

AGCCCCGCTT GCAGCCGCCC AACGGGTACA AGGACACCAC GGTGCCCGGC ATCTGGGTGC 780

CGGATACGCC GTTGTCACAC CGCAACACGC AGCCCGGTTG GGTGGTGGCA CCCGGGATGC 840

AAGGGGTTCA GGTGGGACCG ATCACGCAGG GTTTGCTGAC GCCGGAGTCC CTGGCCGAAC 900

TCATGGGTGG TCCCGATATC GCCCCTCCGT CGTCAGGGCT GCAAACCCCG CCCGGACCCC 960

CGAATGCGTA CGACGAGTAC CCCGTGCTGC CGCCGATCGG TTTACAGGCC CCACAGGTGC 1020

CGATACCACC GCCGCCTCCT GGGCCCGACG TAATCCCGGG TCCGGTGCCA CCGGTCTTGG 1080

CGGCGATCGT GTTCCCAAGA GATCGCCCGG CAGCGTCGGA AAACTTCGAC TACATGGGCC 1140

TCTTGTTGCT GTCGCCGGGC CTGGCGACCT TCCTGTTCGG GGTGTCATCT AGCCCCGCCC 1200

GTGGAACGAT GGCCGATCGG CACGTGTTGA TACCGGCGAT CACCGGCCTG GCGTTGATCG 1260

CGGCATTCGT CGCACATTCG TGGTACCGCA CAGAACATCC GCTCATAGAC ATGCGCTTGT 1320

TCCAGAACCG AGCGGTCGCG CAGGCCAACA TGACGATGAC GGTGCTCTCC CTCGGGCTGT 1380 TTGGCTCCTT CTTGCTGCTC CCGAGCTACC TCCAGCAAGT GTTGCACCAA TCACCGATGC 1440

AATCGGGGGT GCATATCATC CCACAGGGCC TCGGTGCCAT GCTGGCGATG CCGATCGCCG 1500

GAGCGATGAT GGACCGACGG GGACCGGCCA AGATCGTGCT GGTTGGGATC ATGCTGATCG 1560

CTGCGGGGTT GGGCACCTTC GCCTTTGGTG TCGCGCGGCA AGCGGACTAC TTACCCATTC 1620

TGCCGACCGG GCTGGCAATC ATGGGCATGG GCATGGGCTG CTCCATGATG CCACTGTCCG 1680

GGGCGGCAGT GCAGACCCTG GCCCCACATC AGATCGCTCG CGGTTCGACG CTGATCAGCG 1740

TCAACCAGCA GGTGGGCGGT TCGATAGGGA CCGCACTGAT GTCGGTGCTG CTCACCTACC 1800

AGTTCAATCA CAGCGAAATC ATCGCTACTG CAAAGAAAGT CGCACTGACC CCAGAGAGTG 1860

GCGCCGGGCG GGGGGCGGCG GTTGACCCTT CCTCGCTACC GCGCCAAACC AACTTCGCGG 1920

CCCAACTGCT GCATGACCTT TCGCACGCCT ACGCGGTGGT ATTCGTGATA GCGACCGCGC 1980

TAGTGGTCTC GACGCTGATC CCCGCGGCAT TCCTGCCGAA ACAGCAGGCT AGTCATCGAA 2040

GAGCACCGTT GCTATCCGCA TGACGTCTGC TT 2072 (2) INFORMATION FOR SEQ ID NO: 185:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1923 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 185:

TCACCCCGGA GAAGTCGTTC GTCGACGACC TGGACATCGA CTCGCTGTCG ATGGTCGAGA 60

TCGCCGTGCA GACCGAGGAC AAGTACGGCG TCAAGATCCC CGACGAGGAC CTCGCCGGTC 120

TGCGTACCGT CGGTGACGTT GTCGCCTACA TCCAGAAGCT CGAGGAAGAA AACCCGGAGG 180

CGGCTCAGGC GTTGCGCGCG AAGATTGAGT CGGAGAACCC CGATGCGGCA CGAGCAGATC 240

GGTGCGTTTC ACCCACATCG CAAGCTCGAG ACGCCCGTCG TCCTCTTGCA CGCTCAGCCA 300

GGTTGGCGTG TCGCCGCCTT CCAGCAAGTG TTCCCACCAC ACGAAGGGAC CCTCGCGAAA 360

GGTGACTGAT CCGCGGACCA CATAGTCGAT GCCACCGTGG CTGACAATTG CGCCGGGTCC 420

GAGTTGGCGG GGGCCGAATT GCGGCATTGC GTCGAAGGCC AGCGGATCCC GGCGCCCGCC 480 CGGCGTGGCT GGTGTTTTGG GCCGCCGGAT GGCCACGACG AGAACGACGA TGGCGGCGAT 540

GAACAGCGCC ACGGCAATCA CGACCAGCAG ATTTCCCACG CATACCCTCT CGTACCGCTG 600

CGCCGCGGTT GGTCGATCGG TCGCATATCG ATGGCGCCGT TTAACGTAAC AGCTTTCGCG 660

GGACCGGGGG TCACAACGGG CGAGTTGTCC GGCCGGGAAC CCGGCAGGTC TCGGCCGCGG 720

TCACCCCAGC TCACTGGTGC ACCATCCGGG TGTCGGTGAG CGTGCAACTC AAACACACTC 780

AACGGCAACG GTTTCTCAGG TCACCAGCTC AACCTCGACC CGCAATCGCT CGTACGTTTC 840

GACCGCGCGC AGGTCGCGAG TCAGCAGCTT TGCGCCGGCA GCTTTCGCCG TGAAGCCGAC 900

CAGGGCATCG TAGGTTGCGC CACCGGTGAC ATCGTGCTCG GCGAGGTGGT CGGTCAAGCC 960

GCGATATGAG CAGGCATCCA GTGCCAGGTA GTTGCTGGAG GTGATGTCCG CCAAGTAGGC 1020

GTGGACGGCA ACAGGGGCAA TACGATGCGG CGGTGGTAGC CGGGTCAAGA CCGAATAGGT 1080

TTCCACAGCC GCGTGCGCGA TCAGATGGAC GCCACGGTTG AGCGCGCGCA CGGCGGCCTC 1140

GTGCCCTTCG TGCCAGGTCG CGAATCCGGC AACCAGCACG CTGGTGTCTG GTGCGATCAC 1200

CGCCGTGTGC GATCGAGCGT TTCCCGAACG ATTTCGTCGG TCAACGGGGG CAGGGGACGT 1260

TCTGGCCGTG CGACGAGAAC CGAGCCTTCC CGAACGAGTT CGACACCGGT CGGGGCCGGC 1320

TCAATCTCGA TGCGCCCATC GCGCTCGGTG ATCTCCACCT GGTCGTTCCC GCGCAAGCCA 1380

AGGCGCTCGC GAATCCGCTT GGGAATCACC AGACGTCCTG CGACATCGAT GGTTGTTCGC 1440

ATGGTAGGAA ATTTACCATC GCACGTTCCA TAGGCGTGTC CTGCGCGGGA TGTCGGGACG 1500

ATCCGCTAGC GTATCGAACG ATTGTTTCGG AAATGGCTGA GGGAGCGTGC GGTGCGGGTG 1560

ATGGGTGTCG ATCCCGGGTT GACCCGATGC GGGCTGTCGC TCATCGAGAG TGGGCGTGGT 1620

CGGCAGCTCA CCGCGCTGGA TGTCGACGTG GTGCGCACAC CGTCGGATGC GGCCTTGGCG 1680

CAGCGCCTGT TGGCCATCAG CGATGCCGTC GAGCACTGGC TGGACACCCA TCATCCGGAG 1740

GTGGTGGCTA TCGAACGGGT GTTCTCTCAG CTCAACGTGA CCACGGTGAT GGGCACCGCG 1800

CAGGCCGGCG GCGTGATCGC CCTGGCGGCG GCCAAACGTG GTGTCGACGT GCATTTCCAT 1860

ACCCCCAGCG AGGTCAAGGC GGCGGTCACT GGCAACGGTT CCGCAGACAA GGCTCAGGTC 1920

ACC 1923 (2) INFORMATION FOR SEQ ID NO: 186:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1055 base pairs

(B) TYPE: nucleic acid (C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 186:

CTGGCGTGCC AGTGTCACCG GCGATATGAC GTCGGCATTC AATTTCGCGG CCCCGCCGGA 60

CCCGTCGCCA CCCAATCTGG ACCACCCGGT CCGTCAATTG CCGAAGGTCG CCAAGTGCGT 120

GCCCAATGTG GTGCTGGGTT TCTTGAACGA AGGCCTGCCG TATCGGGTGC CCTACCCCCA 180

AACAACGCCA GTCCAGGAAT CCGGTCCCGC GCGGCCGATT CCCAGCGGCA TCTGCTAGCC 240

GGGGATGGTT CAGACGTAAC GGTTGGCTAG GTCGAAACCC GCGCCAGGGC CGCTGGACGG 300

GCTCATGGCA GCGAAATTAG AAAACCCGGG ATATTGTCCG CGGATTGTCA TACGATGCTG 360

AGTGCTTGGT GGTTCGTGTT TAGCCATTGA GTGTGGATGT GTTGAGACCC TGGCCTGGAA 420

GGGGACAACG TGCTTTTGCC TCTTGGTCCG CCTTTGCCGC CCGACGCGGT GGTGGCGAAA 480

CGGGCTGAGT CGGGAATGCT CGGCGGGTTG TCGGTTCCGC TCAGCTGGGG AGTGGCTGTG 540

CCACCCGATG ATTATGACCA CTGGGCGCCT GCGCCGGAGG ACGGCGCCGA TGTCGATGTC 600

CAGGCGGCCG AAGGGGCGGA CGCAGAGGCC GCGGCCATGG ACGAGTGGGA TGAGTGGCAG 660

GCGTGGAACG AGTGGGTGGC GGAGAACGCT GAACCCCGCT TTGAGGTGCC ACGGAGTAGC 720

AGCAGCGTGA TTCCGCATTC TCCGGCGGCC GGCTAGGAGA GGGGGCGCAG ACTGTCGTTA 780

TTTGACCAGT GATCGGCGGT CTCGGTGTTC CCGCGGCCGG CTATGACAAC AGTCAATGTG 840

CATGACAAGT TACAGGTATT AGGTCCAGGT TCAACAAGGA GACAGGCAAC ATGGCAACAC 900

GTTTTATGAC GGATCCGCAC GCGATGCGGG ACATGGCGGG CCGTTTTGAG GTGCACGCCC 960

AGACGGTGGA GGACGAGGCT CGCCGGATGT GGGCGTCCGC GCAAAACATC TCGGGNGCGG 1020

GCTGGAGTGG CATGGCCGAG GCGACCTCGC TAGAC 1055 (2) INFORMATION FOR SEQ ID NO: 187:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 359 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 187:

CCGCCTCGTT GTTGGCATAC TCCGCCGCGG CCGCCTCGAC CGCACTGGCC GTGGCGTGTG 60

TCCGGGCTGA CCACCGGGAT CGCCGAACCA TCCGAGATCA CCTCGCAATG ATCCACCTCG 120

CGCAGCTGGT CACCCAGCCA CCGGGCGGTG TGCGACAGCG CCTGCATCAC CTTGGTATAG 180

CCGTCGCGCC CCAGCCGCAG GAAGTTGTAG TACTGGCCCA CCACCTGGTT ACCGGGACGG 240

GAGAAGTTCA GGGTGAAGGT CGGCATGTCG CCGCCGAGGT AGTTGACCCG GAAAACCAGA 300

TCCTCCGGCA GGTGCTCGGG CCCGCGCCAC ACGACAAACC CGACGCCGGG ATAGGTCAG 359 (2) INFORMATION FOR SEQ ID NO: 188:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 350 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 188:

AACGGGCCCG TGGGCACCGC TCCTCTAAGG GCTCTCGTTG GTCGCATGAA GTGCTGGAAG 60

GATGCATCTT GGCAGATTCC CGCCAGAGCA AAACAGCCGC TAGTCCTAGT CCGAGTCGCC 120

CGCAAAGTTC CTCGAATAAC TCCGTACCCG GAGCGCCAAA CCGGGTCTCC TTCGCTAAGC 180

TGCGCGAACC ACTTGAGGTT CCGGGACTCC TTGACGTCCA GACCGATTCG TTCGAGTGGC 240

TGATCGGTTC GCCGCGCTGG CGCGAATCCG CCGCCGAGCG GGGTGATGTC AACCCAGTGG 300

GTGGCCTGGA AGAGGTGCTC TACGAGCTGT CTCCGATCGA GGACTTCTCC 350 (2) INFORMATION FOR SEQ ID NO: 189:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 679 ammo acids

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 189: Glu Gin Pro Lys Gly Pro Phe Gly Glu Val He Glu Ala Phe Ala Asp 1 5 10 15

Gly Leu Ala Gly Lys Gly Lys Gin He Asn Thr Thr Leu Asn Ser Leu 20 25 30

Ser Gin Ala Leu Asn Ala Leu Asn Glu Gly Arg Gly Asp Phe Phe Ala 35 40 45

Val Val Arg Ser Leu Ala Leu Phe Val Asn Ala Leu His Gin Asp Asp 50 55 60

Gin Gin Phe Val Ala Leu Asn Lys Asn Leu Ala Glu Phe Thr Asp Arg 65 70 75 80

Leu Thr His Ser Asp Ala Asp Leu Ser Asn Ala He Gin Gin Phe Asp 85 90 95

Ser Leu Leu Ala Val Ala Arg Pro Phe Phe Ala Lys Asn Arg Glu Val 100 105 110

Leu Thr His Asp Val Asn Asn Leu Ala Thr Val Thr Thr Thr Leu Leu 115 120 125

Gin Pro Asp Pro Leu Asp Gly Leu Glu Thr Val Leu His He Phe Pro 130 135 140

Thr Leu Ala Ala Asn He Asn Gin Leu Tyr His Pro Thr His Gly Gly 145 150 155 160

Val Val Ser Leu Ser Ala Phe Thr Asn Phe Ala Asn Pro Met Glu Phe 165 170 175

He Cys Ser Ser He Gin Ala Gly Ser Arg Leu Gly Tyr Gin Glu Ser 180 185 190

Ala Glu Leu Cys Ala Gin Tyr Leu Ala Pro Val Leu Asp Ala He Lys 195 200 205

Phe Asn Tyr Phe Pro Phe Gly Leu Asn Val Ala Ser Thr Ala Ser Thr 210 215 220

Leu Pro Lys Glu He Ala Tyr Ser Glu Pro Arg Leu Gin Pro Pro Asn 225 230 235 240

Gly Tyr Lys Asp Thr Thr Val Pro Gly He Trp Val Pro Asp Thr Pro 245 250 255

Leu Ser His Arg Asn Thr Gin Pro Gly Trp Val Val Ala Pro Gly Met 260 265 270

Gin Gly Val Gin Val Gly Pro He Thr Gin Gly Leu Leu Thr Pro Glu 275 280 285 Ser Leu Ala Glu Leu Met Gly Gly Pro Asp He Ala Pro Pro Ser Ser 290 295 300

Gly Leu Gin Thr Pro Pro Gly Pro Pro Asn Ala Tyr Asp Glu Tyr Pro 305 310 315 320

Val Leu Pro Pro He Gly Leu Gin Ala Pro Gin Val Pro He Pro Pro 325 330 335

Pro Pro Pro Gly Pro Asp Val He Pro Gly Pro Val Pro Pro Val Leu 340 345 350

Ala Ala He Val Phe Pro Arg Asp Arg Pro Ala Ala Ser Glu Asn Phe 355 360 365

Asp Tyr Met Gly Leu Leu Leu Leu Ser Pro Gly Leu Ala Thr Phe Leu 370 375 380

Phe Gly Val Ser Ser Ser Pro Ala Arg Gly Thr Met Ala Asp Arg His 385 390 395 400

Val Leu He Pro Ala He Thr Gly Leu Ala Leu He Ala Ala Phe Val 405 410 415

Ala His Ser Trp Tyr Arg Thr Glu His Pro Leu He Asp Met Arg Leu 420 425 430

Phe Gin Asn Arg Ala Val Ala Gin Ala Asn Met Thr Met Thr Val Leu 435 440 445

Ser Leu Gly Leu Phe Gly Ser Phe Leu Leu Leu Pro Ser Tyr Leu Gin 450 455 460

Gin Val Leu His Gin Ser Pro Met Gin Ser Gly Val His He He Pro 465 470 475 480

Gin Gly Leu Gly Ala Met Leu Ala Met Pro He Ala Gly Ala Met Met 485 490 495

Asp Arg Arg Gly Pro Ala Lys He Val Leu Val Gly He Met Leu He 500 505 510

Ala Ala Gly Leu Gly Thr Phe Ala Phe Gly Val Ala Arg Gin Ala Asp 515 520 525

Tyr Leu Pro He Leu Pro Thr Gly Leu Ala He Met Gly Met Gly Met 530 535 540

Gly Cys Ser Met Met Pro Leu Ser Gly Ala Ala Val Gin Thr Leu Ala 545 550 555 560

Pro His Gin He Ala Arg Gly Ser Thr Leu He Ser Val Asn Gin Gin 565 570 575

Val Gly Gly Ser He Gly Thr Ala Leu Met Ser Val Leu Leu Thr Tyr 580 585 590

Gin Phe Asn His Ser Glu He He Ala Thr Ala Lys Lys Val Ala Leu 595 600 605

Thr Pro Glu Ser Gly Ala Gly Arg Gly Ala Ala Val Asp Pro Ser Ser 610 615 620

Leu Pro Arg Gin Thr Asn Phe Ala Ala Gin Leu Leu His Asp Leu Ser 625 630 635 640

His Ala Tyr Ala Val Val Phe Val He Ala Thr Ala Leu Val Val Ser 645 650 655

Thr Leu He Pro Ala Ala Phe Leu Pro Lys Gin Gin Ala Ser His Arg 660 665 670

Arg Ala Pro Leu Leu Ser Ala 675

(2) INFORMATION FOR SEQ ID NO: 190:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 120 amino acids

(B) TYPE: amino acid

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 190:

Thr Pro Glu Lys Ser Phe Val Asp Asp Leu Asp He Asp Ser Leu Ser 1 5 10 15

Met Val Glu He Ala Val Gin Thr Glu Asp Lys Tyr Gly Val Lys He 20 25 30

Pro Asp Glu Asp Leu Ala Gly Leu Arg Thr Val Gly Asp Val Val Ala 35 40 45

Tyr He Gin Lys Leu Glu Glu Glu Asn Pro Glu Ala Ala Gin Ala Leu 50 55 60

Arg Ala Lys He Glu Ser Glu Asn Pro Asp Ala Ala Arg Ala Asp Arg 65 70 75 80

Cys Val Ser Pro Thr Ser Gin Ala Arg Asp Ala Arg Arg Pro Leu Ala 85 90 95

Arg Ser Ala Arg Leu Ala Cys Arg Arg Leu Pro Ala Ser Val Pro Thr 100 105 110 Thr Arg Arg Asp Pro Arg Glu Arg 115 120

(2) INFORMATION FOR SEQ ID NO: 191:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 89 ammo acids

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 191:

Leu Ala Cys Gin Cys His Arg Arg Tyr Asp Val Gly He Gin Phe Arg 1 5 10 15

Gly Pro Ala Gly Pro Val Ala Thr Gin Ser Gly Pro Pro Gly Pro Ser 20 25 30

He Ala Glu Gly Arg Gin Val Arg Ala Gin Cys Gly Ala Gly Phe Leu 35 40 45

Glu Arg Arg Pro Ala Val Ser Gly Ala Leu Pro Pro Asn Asn Ala Ser 50 55 60

Pro Gly He Arg Ser Arg Ala Ala Asp Ser Gin Arg His Leu Leu Ala 65 70 75 80

Gly Asp Gly Ser Asp Val Thr Val Gly 85

(2) INFORMATION FOR SEQ ID NO: 192:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 119 ammo acids

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 192:

Ala Ser Leu Leu Ala Tyr Ser Ala Ala Ala Ala Ser Thr Ala Leu Ala 1 5 10 15

Val Ala Cys Val Arg Ala Asp His Arg Asp Arg Arg Thr He Arg Asp 20 25 30 His Leu Ala Met He His Leu Ala Gin Leu Val Thr Gin Pro Pro Gly 35 40 45

Gly Val Arg Gin Arg Leu His His Leu Gly He Ala Val Ala Pro Gin 50 55 60

Pro Gin Glu Val Val Val Leu Ala His His Leu Val Thr Gly Thr Gly 65 70 75 80

Glu Val Gin Gly Glu Gly Arg His Val Ala Ala Glu Val Val Asp Pro 85 90 95

Glu Asn Gin He Leu Arg Gin Val Leu Gly Pro Ala Pro His Asp Lys 100 105 110

Pro Asp Ala Gly He Gly Gin 115

(2) INFORMATION FOR SEQ ID NO: 193:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 116 ammo acids

(B) TYPE: amino acid

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 193:

Arg Ala Arg Gly His Arg Ser Ser Lys Gly Ser Arg Trp Ser His Glu 1 5 10 15

Val Leu Glu Gly Cys He Leu Ala Asp Ser Arg Gin Ser Lys Thr Ala 20 25 30

Ala Ser Pro Ser Pro Ser Arg Pro Gin Ser Ser Ser Asn Asn Ser Val 35 40 45

Pro Gly Ala Pro Asn Arg Val Ser Phe Ala Lys Leu Arg Glu Pro Leu 50 55 60

Glu Val Pro Gly Leu Leu Asp Val Gin Thr Asp Ser Phe Glu Trp Leu 65 70 75 80

He Gly Ser Pro Arg Trp Arg Glu Ser Ala Ala Glu Arg Gly Asp Val 85 90 95

Asn Pro Val Gly Gly Leu Glu Glu Val Leu Tyr Glu Leu Ser Pro He 100 105 110

Glu Asp Phe Ser 115 (2) INFORMATION FOR SEQ ID NO: 194:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 811 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 194:

TGCTACGCAG CAATCGCTTT GGTGACAGAT GTGGATGCCG GCGTCGCTGC TGGCGATGGC 60

GTGAAAGCCG CCGACGTGTT CGCCGCATTC GGGGAGAACA TCGAACTGCT CAAAAGGCTG 120

GTGCGGGCCG CCATCGATCG GGTCGCCGAC GAGCGCACGT GCACGCACTG TCAACACCAC 180

GCCGGTGTTC CGTTGCCGTT CGAGCTGCCA TGAGGGTGCT GCTGACCGGC GCGGCCGGCT 240

TCATCGGGTC GCGCGTGGAT GCGGCGTTAC GGGCTGCGGG TCACGACGTG GTGGGCGTCG 300

ACGCGCTGCT GCCCGCCGCG CACGGGCCAA ACCCGGTGCT GCCACCGGGC TGCCAGCGGG 360

TCGACGTGCG CGACGCCAGC GCGCTGGCCC CGTTGTTGGC CGGTGTCGAT CTGGTGTGTC 420

ACCAGGCCGC CATGGTGGGT GCCGGCGTCA ACGCCGCCGA CGCACCCGCC TATGGCGGCC 480

ACAACGATTT CGCCACCACG GTGCTGCTGG CGCAGATGTT CGCCGCCGGG GTCCGCCGTT 540

TGGTGCTGGC GTCGTCGATG GTGGTTTACG GGCAGGGGCG CTATGACTGT CCCCAGCATG 600

GACCGGTCGA CCCGCTGCCG CGGCGGCGAG CCGACCTGGA CAATGGGGTC TTCGAGCACC 660

GTTGCCCGGG GTGCGGCGAG CCAGTCATCT GGCAATTGGT CGACGAAGAT GCCCCGTTGC 720

GCCCGCGCAG CCTGTACGCG GCAGCAAGAC CGCGCAGGAG CACTACGCGC TGGCGTGGTC 780 GGAAACGAAT GGCGGTTCCG TGGTGGCGTT G 811

(2) INFORMATION FOR SEQ ID NO: 195:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 966 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 195:

GTCCCGCGAT GTGGCCGAGC ATGACTTTCG GCAACACCGG CGTAGTAGTC GAAGATATCG 60

GACTTTGTGG TCCCGGTGGC GGGATAGAGC ACCTGTCGGC GTTGGTCAGC GTCACCCGTT 120

GCTCGGACGC CGAACCCATG CTTTCAACGT AGCCTGTCGG TCACACAAGT CGCGAGCGTA 180

ACGTCACGGT CAAATATCGC GTGGAATTTC GCCGTGACGT TCCGCTCGCG GACAATCAAG 240

GCATACTCAC TTACATGCGA GCCATTTGGA CGGGTTCGAT CGCCTTCGGG CTGGTGAACG 300

TGCCGGTCAA GGTGTACAGC GCTACCGCAG ACCACGACAT CAGGTTCCAC CAGGTGCACG 360

CCAAGGACAA CGGACGCATC CGGTACAAGC GCGTCTGCGA GGCGTGTGGC GAGGTGGTCG 420

ACTACCGCGA TCTTGCCCGG GCCTACGAGT CCGGCGACGG CCAAATGGTG GCGATCACCG 480

ACGACGACAT CGCCAGCTTG CCTGAAGAAC GCAGCCGGGA GATCGAGGTG TTGGAGTTCG 540

TCCCCGCCGC CGACGTGGAC CCGATGATGT TCGACCGCAG CTACTTTTTG GAGCCTGATT 600

CGAAGTCGTC GAAATCGTAT GTGCTGCTGG CTAAGACACT CGCCGAGACC GACCGGATGG 660

CGATCGTGGA TCGCCCCACC GGCCGTGAAT GCAGGAAAAA TAAGAGCCGC TATCCACAAT 720

TCGGCGTCGA GCTCGGCTAC CACAAACGGT AGAACGATCG AGACATTCCC GAGCTGAAGT 780

GCGGCGCTAT AGAAGCCGCT CTGCGCGATT ATCAAACGCA AAATACGCTT ACTCATGCCA 840

TCGGCGCTGC TCACCCGATG CGACGTTTTT GCCACGCTCC ACCGCCTGCC GCGCGACCTC 900

AAGTGGGCAT GCATCCCACC CGTTCCCGGA AACCGGTTCC GGCGGGTCGG CTCATCGCTT 960

CATCCT 966 (2) INFORMATION FOR SEQ ID NO: 196:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 2367 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 196:

CCGCACCGCC GGCAATACCG CCAGCGCCAC CGTTACCGCC GTTTGCGCCG TTGCCCCCGT 60

TGCCGCCCGT CCCGCCGGCC CCGCCGATGG AGTTCTCATC GCCAAAAGTA CTGGCGTTGC 120

CACCGGAGCC GCCGTTGCCG CCGTCACCGC CAGCCCCGCC GACTCCACCG GCCCCACCGA 180 CTCCGCCGCT GCCACCGTTG CCGCCGTTGC CGATCAACAT GCCGCTGGCG CCACCCTTGC 240

CACCCACGCC ACCGGCTCCG CCCACCCCGC CGACACCAAG CGAGCTGCCG CCGGAGCCAC 300

CATCACCACC TACGCCACCG ACCGCCCAGA CACCAGCGAC CGGGTCTTCG TGAAACGTCG 360

CGGTGCCACC ACCGCCGCCG TTACCGCCAA CCCCACCGGC AACGCCGGCG CCGCCATCCC 420

CGCCGGCCCC GGCGTTGCCG CCGTTGCCGC CGTTGCCGAA CAACAACCCG CCGGCGCCGC 480

CGTTGCCGCC CGCGCCGCCG GTCCCGCCGG CGCCGCCGAC GCCAAGGCCG CTGCCGCCCT 540

TGCCGCCATC ACCACCCTTG CCGCCGACCA CATCGGGTTC TGCCTCGGGG TCTGGGCTGT 600

CAAACCTCGC GATGCCAGCG TTGCCGCCGC TTCCCCCGGG CCCCCCCGTG GCGCCGTCAC 660

CACCGATACC ACCCGCGCCA CCGGCGCCAC CGTTGCCGCC ATCACCGAAT AGCAACCCGC 720

CGGCGCCACC ATTGCCGCCA GCTCCCCCTG CGCCACCGTC GGCGCCGGAG GCGGCACTGG 780

CAGCCCCGTT ACCACCGAAA CCGCCGCTAC CACCGGTAGA GGTGGCAGTG GCGATGTGTA 840

CGAAAGCGCC GCCTCCGGCG CCGCCGCTAC CACCCCCACT GCCGGCGGCT ACACCGTCGG 900

ACCCGTTGCC ACCATCACCG CCAAAGGCGC TCGCAATGTC GCCCTGCGCG ACTCCGCCGT 960

CGCCGCCGTT GCCGCCGCCG CCACCGGCAG CGGCGGTACC GCCGTCACCA CCGGCACCGC 1020

CGGTGGCCTT GCCCGAGCCT GCCGTCGCGG TGGCACCGTC GCCGCCGGTG CCACCGGTCG 1080

GCGTGCCGGC AGTGCCATGG CCGCCCGTGC CGCCGTCGCC GCCGGTTTGA TCACCGATGC 1140

CGGACACATC TGCCGGGCTG TCCCCGGTGC TGGCCGCGGG GCCGGGCGTG GGATTGACCC 1200

CGTTTGCCCC GGCGAGGCCG GCGCCGCCGG TACCACCGGC GCCGCCATGG CCGAACAGCC 1260

CGGCGTTGCC GCCGTTACCG CCCGCACCCC CGATGCCTGC GGCCACGCTG GTGCCGCCGA 1320

CACCGCCGTT GCCGCCGTTG CCCCACAACC ACCCCCCGTT CCCACCGGCA CCGCCGGCCG 1380

CGCCGGTACC ACCGGCCCCG CCGTTGCCGC CGTTGCCGAT CAACCCGGCC GCGCCTCCGC 1440

TGCCGCCGGT TTGACCGAAC CCGCCAGCCG CGCCGTTGCC ACCGTTGCCA AACAGCAACC 1500

CGCCGGCCGC GCCAGGCTGC CCGGGTGCCG TCCCGTCGGC GCCGTTTCCG ATCAACGGGC 1560

GCCCCAAAAG CGCCTCGGTG GGCGCATTCA CCGCACCCAG CAGACTCCGC TCAACAGCGG 1620

CTTCAGTGCT GGCATACCGA CCCGCGGCCG CAGTCAACGC CTGCACAAAC TGCTCGTGAA 1680

ACGCTGCCAC CTGTACGCTG AGCGCCTGAT ACTGCCGAGC ATGGGCCCCG AACAACCCCG 1740

CAATCGCCGC CGACACTTCA TCGGCAGCCG CAGCCACCAC TTCCGTCGTC GGGATCGCCG 1800 CGGCCGCATT AGCCGCGCTC ACCTGCGAAC CAATAGTCGA TAAATCCAAA GCCGCAGTTG 1860

CCAGCAGCTG CGGCGTCGCG ATCACCAAGG ACACCTCGCA CCTCCGGATA CCCCATATCG 1920

CCGCACCGTG TCCCCAGCGG CCACGTGACC TTTGGTCGCT GGCTGGCGGC CCTGACTATG 1980

GCCGCGACGG CCCTCGTTCT GATTCGCCCC GGCGCGCAGC TTGTTGCGCG AGTTGAAGAC 2040

GGGAGGACAG GCCGAGCTTG GTGTAGACGT GGGTCAAGTG GGAATGCACG GTCCGCGGCG 2100

AGATGAATAG GCGGACGCCG ATCTCCTTGT TGCTGAGTCC CTCACCGACC AGTAGAGCCA 2160

CCTCAAGCTC TGTCGGTGTC AACGCGCCCC AGCCACTTGT CGGGCGTTTC CGTGCACCGC 2220

GGCCTCGTTG CGCGTACGCG ATCGCCTCAT CGATCGATAA CGCAGTTCCT TCGGCCCAGG 2280

CATCGTCGAA CTCGCTGTCA CCCATGGATT TTCGAAGGGT GGCTAGCGAC GAGTTACAGC 2340

CCGCCTGGTA GATCCCGAAG CGGACCG 2367 (2) INFORMATION FOR SEQ ID NO: 197:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 376 ammo acids

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 197:

Gin Pro Ala Gly Ala Thr He Ala Ala Ser Ser Pro Cys Ala Thr Val 1 5 10 15

Gly Ala Gly Gly Gly Thr Gly Ser Pro Val Thr Thr Glu Thr Ala Ala 20 25 30

Thr Thr Gly Arg Gly Gly Ser Gly Asp Val Tyr Glu Ser Ala Ala Ser 35 40 45

Gly Ala Ala Ala Thr Thr Pro Thr Ala Gly Gly Tyr Thr Val Gly Pro 50 55 60

Val Ala Thr He Thr Ala Lys Gly Ala Arg Asn Val Ala Leu Arg Asp 65 70 75 80

Ser Ala Val Ala Ala Val Ala Ala Ala Ala Thr Gly Ser Gly Gly Thr 85 90 95

Ala Val Thr Thr Gly Thr Ala Gly Gly Leu Ala Arg Ala Cys Arg Arg 100 105 110 Gly Gly Thr Val Ala Ala Gly Ala Thr Gly Arg Arg Ala Gly Ser Ala 115 120 125

Met Ala Ala Arg Ala Ala Val Ala Ala Gly Leu He Thr Asp Ala Gly 130 135 140

His He Cys Arg Ala Val Pro Gly Ala Gly Arg Gly Ala Gly Arg Gly 145 150 155 160

He Asp Pro Val Cys Pro Gly Glu Ala Gly Ala Ala Gly Thr Thr Gly 165 170 175

Ala Ala Met Ala Glu Gin Pro Gly Val Ala Ala Val Thr Ala Arg Thr 180 185 190

Pro Asp Ala Cys Gly His Ala Gly Ala Ala Asp Thr Ala Val Ala Ala 195 200 205

Val Ala Pro Gin Pro Pro Pro Val Pro Thr Gly Thr Ala Gly Arg Ala 210 215 220

Gly Thr Thr Gly Pro Ala Val Ala Ala Val Ala Asp Gin Pro Gly Arg 225 230 235 240

Ala Ser Ala Ala Ala Gly Leu Thr Glu Pro Ala Ser Arg Ala Val Ala 245 250 255

Thr Val Ala Lys Gin Gin Pro Ala Gly Arg Ala Arg Leu Pro Gly Cys 260 265 270

Arg Pro Val Gly Ala Val Ser Asp Gin Arg Ala Pro Gin Lys Arg Leu 275 280 285

Gly Gly Arg He His Arg Thr Gin Gin Thr Pro Leu Asn Ser Gly Phe 290 295 300

Ser Ala Gly He Pro Thr Arg Gly Arg Ser Gin Arg Leu His Lys Leu 305 310 315 320

Leu Val Lys Arg Cys His Leu Tyr Ala Glu Arg Leu He Leu Pro Ser 325 330 335

Met Gly Pro Glu Gin Pro Arg Asn Arg Arg Arg His Phe He Gly Ser 340 345 350

Arg Ser His His Phe Arg Arg Arg Asp Arg Arg Gly Arg He Ser Arg 355 360 365

Ala His Leu Arg Thr Asn Ser Arg 370 375

(2) INFORMATION FOR SEQ ID NO: 198:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 2852 base pairs (B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 198:

GGCCAAAACG CCCCGGCGAT CGCGGCCACC GAGGCCGCCT ACGACCAGAT GTGGGCCCAG 60

GACGTGGCGG CGATGTTTGG CTACCATGCC GGGGCTTCGG CGGCCGTCTC GGCGTTGACA 120

CCGTTCGGCC AGGCGCTGCC GACCGTGGCG GGCGGCGGTG CGCTGGTCAG CGCGGCCGCG 180

GCTCAGGTGA CCACGCGGGT CTTCCGCAAC CTGGGCTTGG CGAACGTCCG CGAGGGCAAC 240

GTCCGCAACG GTAATGTCCG GAACTTCAAT CTCGGCTCGG CCAACATCGG CAACGGCAAC 300

ATCGGCAGCG GCAACATCGG CAGCTCCAAC ATCGGGTTTG GCAACGTGGG TCCTGGGTTG 360

ACCGCAGCGC TGAACAACAT CGGTTTCGGC AACACCGGCA GCAACAACAT CGGGTTTGGC 420

AACACCGGCA GCAACAACAT CGGGTTCGGC AATACCGGAG ACGGCAACCG AGGTATCGGG 480

CTCACGGGTA GCGGTTTGTT GGGGTTCGGC GGCCTGAACT CGGGCACCGG CAACATCGGT 540

CTGTTCAACT CGGGCACCGG AAACGTCGGC ATCGGCAACT CGGGTACCGG GAACTGGGGC 600

ATTGGCAACT CGGGCAACAG CTACAACACC GGTTTTGGCA ACTCCGGCGA CGCCAACACG 660

GGCTTCTTCA ACTCCGGAAT AGCCAACACC GGCGTCGGCA ACGCCGGCAA CTACAACACC 720

GGTAGCTACA ACCCGGGCAA CAGCAATACC GGCGGCTTCA ACATGGGCCA GTACAACACG 780

GGCTACCTGA ACAGCGGCAA CTACAACACC GGCTTGGCAA ACTCCGGCAA TGTCAACACC 840

GGCGCCTTCA TTACTGGCAA CTTCAACAAC GGCTTCTTGT GGCGCGGCGA CCACCAAGGC 900

CTGATTTTCG GGAGCCCCGG CTTCTTCAAC TCGACCAGTG CGCCGTCGTC GGGATTCTTC 960

AACAGCGGTG CCGGTAGCGC GTCCGGCTTC CTGAACTCCG GTGCCAACAA TTCTGGCTTC 1020

TTCAACTCTT CGTCGGGGGC CATCGGTAAC TCCGGCCTGG CAAACGCGGG CGTGCTGGTA 1080

TCGGGCGTGA TCAACTCGGG CAACACCGTA TCGGGTTTGT TCAACATGAG CCTGGTGGCC 1140

ATCACAACGC CGGCCTTGAT CTCGGGCTTC TTCAACACCG GAAGCAACAT GTCGGGATTT 1200

TTCGGTGGCC CACCGGTCTT CAATCTCGGC CTGGCAAACC GGGGCGTCGT GAACATTCTC 1260

GGCAACGCCA ACATCGGCAA TTACAACATT CTCGGCAGCG GAAACGTCGG TGACTTCAAC 1320

ATCCTTGGCA GCGGCAACCT CGGCAGCCAA AACATCTTGG GCAGCGGCAA CGTCGGCAGC 1380 TTCAATATCG GCAGTGGAAA CATCGGAGTA TTCAATGTCG GTTCCGGAAG CCTGGGAAAC 1440

TACAACATCG GATCCGGAAA CCTCGGGATC TACAACATCG GTTTTGGAAA CGTCGGCGAC 1500

TACAACGTCG GCTTCGGGAA CGCGGGCGAC TTCAACCAAG GCTTTGCCAA CACCGGCAAC 1560

AACAACATCG GGTTCGCCAA CACCGGCAAC AACAACATCG GCATCGGGCT GTCCGGCGAC 1620

AACCAGCAGG GCTTCAATAT TGCTAGCGGC TGGAACTCGG GCACCGGCAA CAGCGGCCTG 1680

TTCAATTCGG GCACCAATAA CGTTGGCATC TTCAACGCGG GCACCGGAAA CGTCGGCATC 1740

GCAAACTCGG GCACCGGGAA CTGGGGTATC GGGAACCCGG GTACCGACAA TACCGGCATC 1800

CTCAATGCTG GCAGCTACAA CACGGGCATC CTCAACGCCG GCGACTTCAA CACGGGCTTC 1860

TACAACACGG GCAGCTACAA CACCGGCGGC TTCAACGTCG GTAACACCAA CACCGGCAAC 1920

TTCAACGTGG GTGACACCAA TACCGGCAGC TATAACCCGG GTGACACCAA CACCGGCTTC 1980

TTCAATCCCG GCAACGTCAA TACCGGCGCT TTCGACACGG GCGACTTCAA CAATGGCTTC 2040

TTGGTGGCGG GCGATAACCA GGGCCAGATT GCCATCGATC TCTCGGTCAC CACTCCATTC 2100

ATCCCCATAA ACGAGCAGAT GGTCATTGAC GTACACAACG TAATGACCTT CGGCGGCAAC 2160

ATGATCACGG TCACCGAGGC CTCGACCGTT TTCCCCCAAA CCTTCTATCT GAGCGGTTTG 2220

TTCTTCTTCG GCCCGGTCAA TCTCAGCGCA TCCACGCTGA CCGTTCCGAC GATCACCCTC 2280

ACCATCGGCG GACCGACGGT GACCGTCCCC ATCAGCATTG TCGGTGCTCT GGAGAGCCGC 2340

ACGATTACCT TCCTCAAGAT CGATCCGGCG CCGGGCATCG GAAATTCGAC CACCAACCCC 2400

TCGTCCGGCT TCTTCAACTC GGGCACCGGT GGCACATCTG GCTTCCAAAA CGTCGGCGGC 2460

GGCAGTTCAG GCGTCTGGAA CAGTGGTTTG AGCAGCGCGA TAGGGAATTC GGGTTTCCAG 2520

AACCTCGGCT CGCTGCAGTC AGGCTGGGCG AACCTGGGCA ACTCCGTATC GGGCTTTTTC 2580

AACACCAGTA CGGTGAACCT CTCCACGCCG GCCAATGTCT CGGGCCTGAA CAACATCGGC 2640

ACCAACCTGT CCGGCGTGTT CCGCGGTCCG ACCGGGACGA TTTTCAACGC GGGCCTTGCC 2700

AACCTGGGCC AGTTGAACAT CGGCAGCGCC TCGTGCCGAA TTCGGCACGA GTTAGATACG 2760

GTTTCAACAA TCATATCCGC GTTTTGCGGC AGTGCATCAG ACGAATCGAA CCCGGGAAGC 2820

GTAAGCGAAT AAACCGAATG GCGGCCTGTC AT 2852

(2) INFORMATION FOR SEQ ID NO: 199:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 943 ammo acids (B) TYPE: amino acid

(C) STRANDEDNESS:

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 199:

Gly Gin Asn Ala Pro Ala He Ala Ala Thr Glu Ala Ala Tyr Asp Gin 1 5 10 15

Met Trp Ala Gin Asp Val Ala Ala Met Phe Gly Tyr His Ala Gly Ala 20 25 30

Ser Ala Ala Val Ser Ala Leu Thr Pro Phe Gly Gin Ala Leu Pro Thr 35 40 45

Val Ala Gly Gly Gly Ala Leu Val Ser Ala Ala Ala Ala Gin Val Thr 50 55 60

Thr Arg Val Phe Arg Asn Leu Gly Leu Ala Asn Val Arg Glu Gly Asn 65 70 75 80

Val Arg Asn Gly Asn Val Arg Asn Phe Asn Leu Gly Ser Ala Asn He 85 90 95

Gly Asn Gly Asn He Gly Ser Gly Asn He Gly Ser Ser Asn He Gly 100 105 110

Phe Gly Asn Val Gly Pro Gly Leu Thr Ala Ala Leu Asn Asn He Gly 115 120 125

Phe Gly Asn Thr Gly Ser Asn Asn He Gly Phe Gly Asn Thr Gly Ser 130 135 140

Asn Asn He Gly Phe Gly Asn Thr Gly Asp Gly Asn Arg Gly He Gly 145 150 155 160

Leu Thr Gly Ser Gly Leu Leu Gly Phe Gly Gly Leu Asn Ser Gly Thr 165 170 175

Gly Asn He Gly Leu Phe Asn Ser Gly Thr Gly Asn Val Gly He Gly 180 185 190

Asn Ser Gly Thr Gly Asn Trp Gly He Gly Asn Ser Gly Asn Ser Tyr 195 200 205

Asn Thr Gly Phe Gly Asn Ser Gly Asp Ala Asn Thr Gly Phe Phe Asn 210 215 220

Ser Gly He Ala Asn Thr Gly Val Gly Asn Ala Gly Asn Tyr Asn Thr 225 230 235 240 Gly Ser Tyr Asn Pro Gly Asn Ser Asn Thr Gly Gly Phe Asn Met Gly 245 250 255

Gin Tyr Asn Thr Gly Tyr Leu Asn Ser Gly Asn Tyr Asn Thr Gly Leu 260 265 270

Ala Asn Ser Gly Asn Val Asn Thr Gly Ala Phe He Thr Gly Asn Phe 275 280 285

Asn Asn Gly Phe Leu Trp Arg Gly Asp His Gin Gly Leu He Phe Gly 290 295 300

Ser Pro Gly Phe Phe Asn Ser Thr Ser Ala Pro Ser Ser Gly Phe Phe 305 310 315 320

Asn Ser Gly Ala Gly Ser Ala Ser Gly Phe Leu Asn Ser Gly Ala Asn 325 330 335

Asn Ser Gly Phe Phe Asn Ser Ser Ser Gly Ala He Gly Asn Ser Gly 340 345 350

Leu Ala Asn Ala Gly Val Leu Val Ser Gly Val He Asn Ser Gly Asn 355 360 365

Thr Val Ser Gly Leu Phe Asn Met Ser Leu Val Ala He Thr Thr Pro 370 375 380

Ala Leu He Ser Gly Phe Phe Asn Thr Gly Ser Asn Met Ser Gly Phe 385 390 395 400

Phe Gly Gly Pro Pro Val Phe Asn Leu Gly Leu Ala Asn Arg Gly Val 405 410 415

Val Asn He Leu Gly Asn Ala Asn He Gly Asn Tyr Asn He Leu Gly 420 425 430

Ser Gly Asn Val Gly Asp Phe Asn He Leu Gly Ser Gly Asn Leu Gly 435 440 445

Ser Gin Asn He Leu Gly Ser Gly Asn Val Gly Ser Phe Asn He Gly 450 455 460

Ser Gly Asn He Gly Val Phe Asn Val Gly Ser Gly Ser Leu Gly Asn 465 470 475 480

Tyr Asn He Gly Ser Gly Asn Leu Gly He Tyr Asn He Gly Phe Gly 485 490 495

Asn Val Gly Asp Tyr Asn Val Gly Phe Gly Asn Ala Gly Asp Phe Asn 500 505 510

Gin Gly Phe Ala Asn Thr Gly Asn Asn Asn He Gly Phe Ala Asn Thr 515 520 525

Gly Asn Asn Asn He Gly He Gly Leu Ser Gly Asp Asn Gin Gin Gly 530 535 540

Phe Asn He Ala Ser Gly Trp Asn Ser Gly Thr Gly Asn Ser Gly Leu 545 550 555 560

Phe Asn Ser Gly Thr Asn Asn Val Gly He Phe Asn Ala Gly Thr Gly 565 570 575

Asn Val Gly He Ala Asn Ser Gly Thr Gly Asn Trp Gly He Gly Asn 580 585 590

Pro Gly Thr Asp Asn Thr Gly He Leu Asn Ala Gly Ser Tyr Asn Thr 595 600 605

Gly He Leu Asn Ala Gly Asp Phe Asn Thr Gly Phe Tyr Asn Thr Gly 610 615 620

Ser Tyr Asn Thr Gly Gly Phe Asn Val Gly Asn Thr Asn Thr Gly Asn 625 630 635 640

Phe Asn Val Gly Asp Thr Asn Thr Gly Ser Tyr Asn Pro Gly Asp Thr 645 650 655

Asn Thr Gly Phe Phe Asn Pro Gly Asn Val Asn Thr Gly Ala Phe Asp 660 665 670

Thr Gly Asp Phe Asn Asn Gly Phe Leu Val Ala Gly Asp Asn Gin Gly 675 680 685

Gin He Ala He Asp Leu Ser Val Thr Thr Pro Phe He Pro He Asn 690 695 700

Glu Gin Met Val He Asp Val His Asn Val Met Thr Phe Gly Gly Asn 705 710 715 720

Met He Thr Val Thr Glu Ala Ser Thr Val Phe Pro Gin Thr Phe Tyr 725 730 735

Leu Ser Gly Leu Phe Phe Phe Gly Pro Val Asn Leu Ser Ala Ser Thr 740 745 750

Leu Thr Val Pro Thr He Thr Leu Thr He Gly Gly Pro Thr Val Thr 755 760 765

Val Pro He Ser He Val Gly Ala Leu Glu Ser Arg Thr He Thr Phe 770 775 780

Leu Lys He Asp Pro Ala Pro Gly He Gly Asn Ser Thr Thr Asn Pro 785 790 795 800

Ser Ser Gly Phe Phe Asn Ser Gly Thr Gly Gly Thr Ser Gly Phe Gin 805 810 815

Asn Val Gly Gly Gly Ser Ser Gly Val Trp Asn Ser Gly Leu Ser Ser 820 825 830 Ala He Gly Asn Ser Gly Phe Gin Asn Leu Gly Ser Leu Gin Ser Gly 835 840 845

Trp Ala Asn Leu Gly Asn Ser Val Ser Gly Phe Phe Asn Thr Ser Thr 850 855 860

Val Asn Leu Ser Thr Pro Ala Asn Val Ser Gly Leu Asn Asn He Gly 865 870 875 880

Thr Asn Leu Ser Gly Val Phe Arg Gly Pro Thr Gly Thr He Phe Asn 885 890 895

Ala Gly Leu Ala Asn Leu Gly Gin Leu Asn He Gly Ser Ala Ser Cys 900 905 910

Arg He Arg His Glu Leu Asp Thr Val Ser Thr He He Ser Ala Phe 915 920 925

Cys Gly Ser Ala Ser Asp Glu Ser Asn Pro Gly Ser Val Ser Glu 930 935 940

12) INFORMATION FOR SEQ ID NO: 200:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 53 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:200: GGATCCATAT GGGCCATCAT CATCATCATC ACGTGATCGA CATCATCGGG ACC 53

(2) INFORMATION FOR SEQ ID NO:201:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 42 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 201: CCTGAATTCA GGCCTCGGTT GCGCCGGCCT CATCTTGAAC GA 42

(2) INFORMATION FOR SEQ ID NO: 202: (l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 31 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 202: GGATCCTGCA GGCTCGAAAC CACCGAGCGG T 31

(2) INFORMATION FOR SEQ ID NO:203:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 31 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 203: CTCTGAATTC AGCGCTGGAA ATCGTCGCGA T 31

(2) INFORMATION FOR SEQ ID NO: 204:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 33 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi ) SEQUENCE DESCRIPTION: SEQ ID NO: 204: GGATCCAGCG CTGAGATGAA GACCGATGCC GCT 33

(2) INFORMATION FOR SEQ ID NO: 205:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 38 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 205: GGATATCTGC AGAATTCAGG TTTAAAGCCC ATTTGCGA 38

(2) INFORMATION FOR SEQ ID NO: 206:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 30 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:206: CCGCATGCGA GCCACGTGCC CACAACGGCC 30

(2) INFORMATION FOR SEQ ID NO: 207:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 37 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:207: CTTCATGGAA TTCTCAGGCC GGTAAGGTCC GCTGCGG 37

(2) INFORMATION FOR SEQ ID NO: 208:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 7676 base pairs

(B) TYPE: nucleic acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 208: TGGCGAATGG GACGCGCCCT GTAGCGGCGC ATTAAGCGCG GCGGGTGTGG TGGTTACGCG 60 CAGCGTGACC GCTACACTTG CCAGCGCCCT AGCGCCCGCT CCTTTCGCTT TCTTCCCTTC 120

CTTTCTCGCC ACGTTCGCCG GCTTTCCCCG TCAAGCTCTA AATCGGGGGC TCCCTTTAGG 180

GTTCCGATTT AGTGCTTTAC GGCACCTCGA CCCCAAAAAA CTTGATTAGG GTGATGGTTC 240

ACGTAGTGGG CCATCGCCCT GATAGACGGT TTTTCGCCCT TTGACGTTGG AGTCCACGTT 300

CTTTAATAGT GGACTCTTGT TCCAAACTGG AACAACACTC AACCCTATCT CGGTCTATTC 360

TTTTGATTTA TAAGGGATTT TGCCGATTTC GGCCTATTGG TTAAAAAATG AGCTGATTTA 420

ACAAAAATTT AACGCGAATT TTAACAAAAT ATTAACGTTT ACAATTTCAG GTGGCACTTT 480

TCGGGGAAAT GTGCGCGGAA CCCCTATTTG TTTATTTTTC TAAATACATT CAAATATGTA 540

TCCGCTCATG AATTAATTCT TAGAAAAACT CATCGAGCAT CAAATGAAAC TGCAATTTAT 600

TCATATCAGG ATTATCAATA CCATATTTTT GAAAAAGCCG TTTCTGTAAT GAAGGAGAAA 660

ACTCACCGAG GCAGTTCCAT AGGATGGCAA GATCCTGGTA TCGGTCTGCG ATTCCGACTC 720

GTCCAACATC AATACAACCT ATTAATTTCC CCTCGTCAAA AATAAGGTTA TCAAGTGAGA 780

AATCACCATG AGTGACGACT GAATCCGGTG AGAATGGCAA AAGTTTATGC ATTTCTTTCC 840

AGACTTGTTC AACAGGCCAG CCATTACGCT CGTCATCAAA ATCACTCGCA TCAACCAAAC 900

CGTTATTCAT TCGTGATTGC GCCTGAGCGA GACGAAATAC GCGATCGCTG TTAAAAGGAC 960

AATTACAAAC AGGAATCGAA TGCAACCGGC GCAGGAACAC TGCCAGCGCA TCAACAATAT 1020

TTTCACCTGA ATCAGGATAT TCTTCTAATA CCTGGAATGC TGTTTTCCCG GGGATCGCAG 1080

TGGTGAGTAA CCATGCATCA TCAGGAGTAC GGATAAAATG CTTGATGGTC GGAAGAGGCA 1140

TAAATTCCGT CAGCCAGTTT AGTCTGACCA TCTCATCTGT AACATCATTG GCAACGCTAC 1200

CTTTGCCATG TTTCAGAAAC AACTCTGGCG CATCGGGCTT CCCATACAAT CGATAGATTG 1260

TCGCACCTGA TTGCCCGACA TTATCGCGAG CCCATTTATA CCCATATAAA TCAGCATCCA 1320

TGTTGGAATT TAATCGCGGC CTAGAGCAAG ACGTTTCCCG TTGAATATGG CTCATAACAC 1380

CCCTTGTATT ACTGTTTATG TAAGCAGACA GTTTTATTGT TCATGACCAA AATCCCTTAA 1440

CGTGAGTTTT CGTTCCACTG AGCGTCAGAC CCCGTAGAAA AGATCAAAGG ATCTTCTTGA 1500

GATCCTTTTT TTCTGCGCGT AATCTGCTGC TTGCAAACAA AAAAACCACC GCTACCAGCG 1560

GTGGTTTGTT TGCCGGATCA AGAGCTACCA ACTCTTTTTC CGAAGGTAAC TGGCTTCAGC 1620

AGAGCGCAGA TACCAAATAC TGTCCTTCTA GTGTAGCCGT AGTTAGGCCA CCACTTCAAG 1680 AACTCTGTAG CACCGCCTAC ATACCTCGCT CTGCTAATCC TGTTACCAGT GGCTGCTGCC 1740

AGTGGCGATA AGTCGTGTCT TACCGGGTTG GACTCAAGAC GATAGTTACC GGATAAGGCG 1800

CAGCGGTCGG GCTGAACGGG GGGTTCGTGC ACACAGCCCA GCTTGGAGCG AACGACCTAC 1860

ACCGAACTGA GATACCTACA GCGTGAGCTA TGAGAAAGCG CCACGCTTCC CGAAGGGAGA 1920

AAGGCGGACA GGTATCCGGT AAGCGGCAGG GTCGGAACAG GAGAGCGCAC GAGGGAGCTT 1980

CCAGGGGGAA ACGCCTGGTA TCTTTATAGT CCTGTCGGGT TTCGCCACCT CTGACTTGAG 2040

CGTCGATTTT TGTGATGCTC GTCAGGGGGG CGGAGCCTAT GGAAAAACGC CAGCAACGCG 2100

GCCTTTTTAC GGTTCCTGGC CTTTTGCTGG CCTTTTGCTC ACATGTTCTT TCCTGCGTTA 2160

TCCCCTGATT CTGTGGATAA CCGTATTACC GCCTTTGAGT GAGCTGATAC CGCTCGCCGC 2220

AGCCGAACGA CCGAGCGCAG CGAGTCAGTG AGCGAGGAAG CGGAAGAGCG CCTGATGCGG 2280

TATTTTCTCC TTACGCATCT GTGCGGTATT TCACACCGCA TATATGGTGC ACTCTCAGTA 2340

CAATCTGCTC TGATGCCGCA TAGTTAAGCC AGTATACACT CCGCTATCGC TACGTGACTG 2400

GGTCATGGCT GCGCCCCGAC ACCCGCCAAC ACCCGCTGAC GCGCCCTGAC GGGCTTGTCT 2460

GCTCCCGGCA TCCGCTTACA GACAAGCTGT GACCGTCTCC GGGAGCTGCA TGTGTCAGAG 2520

GTTTTCACCG TCATCACCGA AACGCGCGAG GCAGCTGCGG TAAAGCTCAT CAGCGTGGTC 2580

GTGAAGCGAT TCACAGATGT CTGCCTGTTC ATCCGCGTCC AGCTCGTTGA GTTTCTCCAG 2640

AAGCGTTAAT GTCTGGCTTC TGATAAAGCG GGCCATGTTA AGGGCGGTTT TTTCCTGTTT 2700

GGTCACTGAT GCCTCCGTGT AAGGGGGATT TCTGTTCATG GGGGTAATGA TACCGATGAA 2760

ACGAGAGAGG ATGCTCACGA TACGGGTTAC TGATGATGAA CATGCCCGGT TACTGGAACG 2820

TTGTGAGGGT AAACAACTGG CGGTATGGAT GCGGCGGGAC CAGAGAAAAA TCACTCAGGG 2880

TCAATGCCAG CGCTTCGTTA ATACAGATGT AGGTGTTCCA CAGGGTAGCC AGCAGCATCC 2940

TGCGATGCAG ATCCGGAACA TAATGGTGCA GGGCGCTGAC TTCCGCGTTT CCAGACTTTA 3000

CGAAACACGG AAACCGAAGA CCATTCATGT TGTTGCTCAG GTCGCAGACG TTTTGCAGCA 3060

GCAGTCGCTT CACGTTCGCT CGCGTATCGG TGATTCATTC TGCTAACCAG TAAGGCAACC 3120

CCGCCAGCCT AGCCGGGTCC TCAACGACAG GAGCACGATC ATGCGCACCC GTGGGGCCGC 3180

CATGCCGGCG ATAATGGCCT GCTTCTCGCC GAAACGTTTG GTGGCGGGAC CAGTGACGAA 3240

GGCTTGAGCG AGGGCGTGCA AGATTCCGAA TACCGCAAGC GACAGGCCGA TCATCGTCGC 3300

GCTCCAGCGA AAGCGGTCCT CGCCGAAAAT GACCCAGAGC GCTGCCGGCA CCTGTCCTAC 3360 GAGTTGCATG ATAAAGAAGA CAGTCATAAG TGCGGCGACG ATAGTCATGC CCCGCGCCCA 3420

CCGGAAGGAG CTGACTGGGT TGAAGGCTCT CAAGGGCATC GGTCGAGATC CCGGTGCCTA 3480

ATGAGTGAGC TAACTTACAT TAATTGCGTT GCGCTCACTG CCCGCTTTCC AGTCGGGAAA 3540

CCTGTCGTGC CAGCTGCATT AATGAATCGG CCAACGCGCG GGGAGAGGCG GTTTGCGTAT 3600

TGGGCGCCAG GGTGGTTTTT CTTTTCACCA GTGAGACGGG CAACAGCTGA TTGCCCTTCA 3660

CCGCCTGGCC CTGAGAGAGT TGCAGCAAGC GGTCCACGCT GGTTTGCCCC AGCAGGCGAA 3720

AATCCTGTTT GATGGTGGTT AACGGCGGGA TATAACATGA GCTGTCTTCG GTATCGTCGT 3780

ATCCCACTAC CGAGATATCC GCACCAACGC GCAGCCCGGA CTCGGTAATG GCGCGCATTG 3840

CGCCCAGCGC CATCTGATCG TTGGCAACCA GCATCGCAGT GGGAACGATG CCCTCATTCA 3900

GCATTTGCAT GGTTTGTTGA AAACCGGACA TGGCACTCCA GTCGCCTTCC CGTTCCGCTA 3960

TCGGCTGAAT TTGATTGCGA GTGAGATATT TATGCCAGCC AGCCAGACGC AGACGCGCCG 4020

AGACAGAACT TAATGGGCCC GCTAACAGCG CGATTTGCTG GTGACCCAAT GCGACCAGAT 4080

GCTCCACGCC CAGTCGCGTA CCGTCTTCAT GGGAGAAAAT AATACTGTTG ATGGGTGTCT 4140

GGTCAGAGAC ATCAAGAAAT AACGCCGGAA CATTAGTGCA GGCAGCTTCC ACAGCAATGG 4200

CATCCTGGTC ATCCAGCGGA TAGTTAATGA TCAGCCCACT GACGCGTTGC GCGAGAAGAT 4260

TGTGCACCGC CGCTTTACAG GCTTCGACGC CGCTTCGTTC TACCATCGAC ACCACCACGC 4320

TGGCACCCAG TTGATCGGCG CGAGATTTAA TCGCCGCGAC AATTTGCGAC GGCGCGTGCA 4380

GGGCCAGACT GGAGGTGGCA ACGCCAATCA GCAACGACTG TTTGCCCGCC AGTTGTTGTG 4440

CCACGCGGTT GGGAATGTAA TTCAGCTCCG CCATCGCCGC TTCCACTTTT TCCCGCGTTT 4500

TCGCAGAAAC GTGGCTGGCC TGGTTCACCA CGCGGGAAAC GGTCTGATAA GAGACACCGG 4560

CATACTCTGC GACATCGTAT AACGTTACTG GTTTCACATT CACCACCCTG AATTGACTCT 4620

CTTCCGGGCG CTATCATGCC ATACCGCGAA AGGTTTTGCG CCATTCGATG GTGTCCGGGA 4680

TCTCGACGCT CTCCCTTATG CGACTCCTGC ATTAGGAAGC AGCCCAGTAG TAGGTTGAGG 4740

CCGTTGAGCA CCGCCGCCGC AAGGAATGGT GCATGCAAGG AGATGGCGCC CAACAGTCCC 4800

CCGGCCACGG GGCCTGCCAC CATACCCACG CCGAAACAAG CGCTCATGAG CCCGAAGTGG 4860

CGAGCCCGAT CTTCCCCATC GGTGATGTCG GCGATATAGG CGCCAGCAAC CGCACCTGTG 4920

GCGCCGGTGA TGCCGGCCAC GATGCGTCCG GCGTAGAGGA TCGAGATCTC GATCCCGCGA 4980 AATTAATACG ACTCACTATA GGGGAATTGT GAGCGGATAA CAATTCCCCT CTAGAAATAA 5040

TTTTGTTTAA CTTTAAGAAG GAGATATACA TATGGGCCAT CATCATCATC ATCACGTGAT 5100

CGACATCATC GGGACCAGCC CCACATCCTG GGAACAGGCG GCGGCGGAGG CGGTCCAGCG 5160

GGCGCGGGAT AGCGTCGATG ACATCCGCGT CGCTCGGGTC ATTGAGCAGG ACATGGCCGT 5220

GGACAGCGCC GGCAAGATCA CCTACCGCAT CAAGCTCGAA GTGTCGTTCA AGATGAGGCC 5280

GGCGCAACCG AGGGGCTCGA AACCACCGAG CGGTTCGCCT GAAACGGGCG CCGGCGCCGG 5340

TACTGTCGCG ACTACCCCCG CGTCGTCGCC GGTGACGTTG GCGGAGACCG GTAGCACGCT 5400

GCTCTACCCG CTGTTCAACC TGTGGGGTCC GGCCTTTCAC GAGAGGTATC CGAACGTCAC 5460

GATCACCGCT CAGGGCACCG GTTCTGGTGC CGGGATCGCG CAGGCCGCCG CCGGGACGGT 5520

CAACATTGGG GCCTCCGACG CCTATCTGTC GGAAGGTGAT ATGGCCGCGC ACAAGGGGCT 5580

GATGAACATC GCGCTAGCCA TCTCCGCTCA GCAGGTCAAC TACAACCTGC CCGGAGTGAG 5640

CGAGCACCTC AAGCTGAACG GAAAAGTCCT GGCGGCCATG TACCAGGGCA CCATCAAAAC 5700

CTGGGACGAC CCGCAGATCG CTGCGCTCAA CCCCGGCGTG AACCTGCCCG GCACCGCGGT 5760

AGTTCCGCTG CACCGCTCCG ACGGGTCCGG TGACACCTTC TTGTTCACCC AGTACCTGTC 5820

CAAGCAAGAT CCCGAGGGCT GGGGCAAGTC GCCCGGCTTC GGCACCACCG TCGACTTCCC 5880

GGCGGTGCCG GGTGCGCTGG GTGAGAACGG CAACGGCGGC ATGGTGACCG GTTGCGCCGA 5940

GACACCGGGC TGCGTGGCCT ATATCGGCAT CAGCTTCCTC GACCAGGCCA GTCAACGGGG 6000

ACTCGGCGAG GCCCAACTAG GCAATAGCTC TGGCAATTTC TTGTTGCCCG ACGCGCAAAG 6060

CATTCAGGCC GCGGCGGCTG GCTTCGCATC GAAAACCCCG GCGAACCAGG CGATTTCGAT 6120

GATCGACGGG CCCGCCCCGG ACGGCTACCC GATCATCAAC TACGAGTACG CCATCGTCAA 6180

CAACCGGCAA AAGGACGCCG CCACCGCGCA GACCTTGCAG GCATTTCTGC ACTGGGCGAT 6240

CACCGACGGC AACAAGGCCT CGTTCCTCGA CCAGGTTCAT TTCCAGCCGC TGCCGCCCGC 6300

GGTGGTGAAG TTGTCTGACG CGTTGATCGC GACGATTTCC AGCGCTGAGA TGAAGACCGA 6360

TGCCGCTACC CTCGCGCAGG AGGCAGGTAA TTTCGAGCGG ATCTCCGGCG ACCTGAAAAC 6420

CCAGATCGAC CAGGTGGAGT CGACGGCAGG TTCGTTGCAG GGCCAGTGGC GCGGCGCGGC 6480

GGGGACGGCC GCCCAGGCCG CGGTGGTGCG CTTCCAAGAA GCAGCCAATA AGCAGAAGCA 6540

GGAACTCGAC GAGATCTCGA CGAATATTCG TCAGGCCGGC GTCCAATACT CGAGGGCCGA 6600

CGAGGAGCAG CAGCAGGCGC TGTCCTCGCA AATGGGCTTT GTGCCCACAA CGGCCGCCTC 6660 GCCGCCGTCG ACCGCTGCAG CGCCACCCGC ACCGGCGACA CCTGTTGCCC CCCCACCACC 6720

GGCCGCCGCC AACACGCCGA ATGCCCAGCC GGGCGATCCC AACGCAGCAC CTCCGCCGGC 6780

CGACCCGAAC GCACCGCCGC CACCTGTCAT TGCCCCAAAC GCACCCCAAC CTGTCCGGAT 6840

CGACAACCCG GTTGGAGGAT TCAGCTTCGC GCTGCCTGCT GGCTGGGTGG AGTCTGACGC 6900

CGCCCACTTC GACTACGGTT CAGCACTCCT CAGCAAAACC ACCGGGGACC CGCCATTTCC 6960

CGGACAGCCG CCGCCGGTGG CCAATGACAC CCGTATCGTG CTCGGCCGGC TAGACCAAAA 7020

GCTTTACGCC AGCGCCGAAG CCACCGACTC CAAGGCCGCG GCCCGGTTGG GCTCGGACAT 7080

GGGTGAGTTC TATATGCCCT ACCCGGGCAC CCGGATCAAC CAGGAAACCG TCTCGCTTGA 7140

CGCCAACGGG GTGTCTGGAA GCGCGTCGTA TTACGAAGTC AAGTTCAGCG ATCCGAGTAA 7200

GCCGAACGGC CAGATCTGGA CGGGCGTAAT CGGCTCGCCC GCGGCGAACG CACCGGACGC 7260

CGGGCCCCCT CAGCGCTGGT TTGTGGTATG GCTCGGGACC GCCAACAACC CGGTGGACAA 7320

GGGCGCGGCC AAGGCGCTGG CCGAATCGAT CCGGCCTTTG GTCGCCCCGC CGCCGGCGCC 7380

GGCACCGGCT CCTGCAGAGC CCGCTCCGGC GCCGGCGCCG GCCGGGGAAG TCGCTCCTAC 7440

CCCGACGACA CCGACACCGC AGCGGACCTT ACCGGCCTGA GAATTCTGCA GATATCCATC 7500

ACACTGGCGG CCGCTCGAGC ACCACCACCA CCACCACTGA GATCCGGCTG CTAACAAAGC 7560

CCGAAAGGAA GCTGAGTTGG CTGCTGCCAC CGCTGAGCAA TAACTAGCAT AACCCCTTGG 7620

GGCCTCTAAA CGGGTCTTGA GGGGTTTTTT GCTGAAAGGA GGAACTATAT CCGGAT 7676 (2) INFORMATION FOR SEQ ID NO: 209:

(l) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 802 ammo acids

(B) TYPE: ammo acid

(C) STRANDEDNESS: single

(D) TOPOLOGY: linear

(xi ) SEQUENCE DESCRIPTION: SEQ ID NO: 209:

Met Gly His His His His His His Val He Asp He He Gly Thr Ser 1 5 10 15

Pro Thr Ser Trp Glu Gin Ala Ala Ala Glu Ala Val Gin Arg Ala Arg 20 25 30 Asp Ser Val Asp Asp He Arg Val Ala Arg Val He Glu Gin Asp Met 35 40 45

Ala Val Asp Ser Ala Gly Lys He Thr Tyr Arg He Lys Leu Glu Val 50 55 60

Ser Phe Lys Met Arg Pro Ala Gin Pro Arg Gly Ser Lys Pro Pro Ser 65 70 75 80

Gly Ser Pro Glu Thr Gly Ala Gly Ala Gly Thr Val Ala Thr Thr Pro 85 90 95

Ala Ser Ser Pro Val Thr Leu Ala Glu Thr Gly Ser Thr Leu Leu Tyr 100 105 110

Pro Leu Phe Asn Leu Trp Gly Pro Ala Phe His Glu Arg Tyr Pro Asn 115 120 125

Val Thr He Thr Ala Gin Gly Thr Gly Ser Gly Ala Gly He Ala Gin 130 135 140

Ala Ala Ala Gly Thr Val Asn He Gly Ala Ser Asp Ala Tyr Leu Ser 145 150 155 160

Glu Gly Asp Met Ala Ala His Lys Gly Leu Met Asn He Ala Leu Ala 165 170 175

He Ser Ala Gin Gin Val Asn Tyr Asn Leu Pro Gly Val Ser Glu His 180 185 190

Leu Lys Leu Asn Gly Lys Val Leu Ala Ala Met Tyr Gin Gly Thr He 195 200 205

Lys Thr Trp Asp Asp Pro Gin He Ala Ala Leu Asn Pro Gly Val Asn 210 215 220

Leu Pro Gly Thr Ala Val Val Pro Leu His Arg Ser Asp Gly Ser Gly 225 230 235 240

Asp Thr Phe Leu Phe Thr Gin Tyr Leu Ser Lys Gin Asp Pro Glu Gly 245 250 255

Trp Gly Lys Ser Pro Gly Phe Gly Thr Thr Val Asp Phe Pro Ala Val 260 265 270

Pro Gly Ala Leu Gly Glu Asn Gly Asn Gly Gly Met Val Thr Gly Cys 275 280 285

Ala Glu Thr Pro Gly Cys Val Ala Tyr He Gly He Ser Phe Leu Asp 290 295 300

Gin Ala Ser Gin Arg Gly Leu Gly Glu Ala Gin Leu Gly Asn Ser Ser 305 310 315 320

Gly Asn Phe Leu Leu Pro Asp Ala Gin Ser He Gin Ala Ala Ala Ala 325 330 335

Gly Phe Ala Ser Lys Thr Pro Ala Asn Gin Ala He Ser Met He Asp 340 345 350

Gly Pro Ala Pro Asp Gly Tyr Pro He He Asn Tyr Glu Tyr Ala He 355 360 365

Val Asn Asn Arg Gin Lys Asp Ala Ala Thr Ala Gin Thr Leu Gin Ala 370 375 380

Phe Leu His Trp Ala He Thr Asp Gly Asn Lys Ala Ser Phe Leu Asp 385 390 395 400

Gin Val His Phe Gin Pro Leu Pro Pro Ala Val Val Lys Leu Ser Asp 405 410 415

Ala Leu He Ala Thr He Ser Ser Ala Glu Met Lys Thr Asp Ala Ala 420 425 430

Thr Leu Ala Gin Glu Ala Gly Asn Phe Glu Arg He Ser Gly Asp Leu 435 440 445

Lys Thr Gin He Asp Gin Val Glu Ser Thr Ala Gly Ser Leu Gin Gly 450 455 460

Gin Trp Arg Gly Ala Ala Gly Thr Ala Ala Gin Ala Ala Val Val Arg 465 470 475 480

Phe Gin Glu Ala Ala Asn Lys Gin Lys Gin Glu Leu Asp Glu He Ser 485 490 495

Thr Asn He Arg Gin Ala Gly Val Gin Tyr Ser Arg Ala Asp Glu Glu 500 505 510

Gin Gin Gin Ala Leu Ser Ser Gin Met Gly Phe Val Pro Thr Thr Ala 515 520 525

Ala Ser Pro Pro Ser Thr Ala Ala Ala Pro Pro Ala Pro Ala Thr Pro 530 535 540

Val Ala Pro Pro Pro Pro Ala Ala Ala Asn Thr Pro Asn Ala Gin Pro 545 550 555 560

Gly Asp Pro Asn Ala Ala Pro Pro Pro Ala Asp Pro Asn Ala Pro Pro 565 570 575

Pro Pro Val He Ala Pro Asn Ala Pro Gin Pro Val Arg He Asp Asn 580 585 590

Pro Val Gly Gly Phe Ser Phe Ala Leu Pro Ala Gly Trp Val Glu Ser 595 600 605

Asp Ala Ala His Phe Asp Tyr Gly Ser Ala Leu Leu Ser Lys Thr Thr 610 615 620 Gly Asp Pro Pro Phe Pro Gly Gin Pro Pro Pro Val Ala Asn Asp Thr 625 630 635 640

Arg He Val Leu Gly Arg Leu Asp Gin Lys Leu Tyr Ala Ser Ala Glu 645 650 655

Ala Thr Asp Ser Lys Ala Ala Ala Arg Leu Gly Ser Asp Met Gly Glu 660 665 670

Phe Tyr Met Pro Tyr Pro Gly Thr Arg He Asn Gin Glu Thr Val Ser 675 680 685

Leu Asp Ala Asn Gly Val Ser Gly Ser Ala Ser Tyr Tyr Glu Val Lys 690 695 700

Phe Ser Asp Pro Ser Lys Pro Asn Gly Gin He Trp Thr Gly Val He 705 710 715 720

Gly Ser Pro Ala Ala Asn Ala Pro Asp Ala Gly Pro Pro Gin Arg Trp 725 730 735

Phe Val Val Trp Leu Gly Thr Ala Asn Asn Pro Val Asp Lys Gly Ala 740 745 750

Ala Lys Ala Leu Ala Glu Ser He Arg Pro Leu Val Ala Pro Pro Pro 755 760 765

Ala Pro Ala Pro Ala Pro Ala Glu Pro Ala Pro Ala Pro Ala Pro Ala 770 775 780

Gly Glu Val Ala Pro Thr Pro Thr Thr Pro Thr Pro Gin Arg Thr Leu 785 790 795 800

Pro Ala

Claims

CLAIMS We claim:

1. A polypeptide comprising an antigenic portion of a soluble

M. tuberculosis antigen, or a variant of said antigen that differs only in conservative substitutions and/or modifications, wherein said antigen has an N-terminal sequence selected from the group consisting of:

(a) Asp-Pro-Val-Asp-Ala-Val-Ile-Asn-Thr-Thr-Cys-Asn-Tyr-Gly-Gln- Val-Val- Ala-Ala-Leu (SEQ ID NO: 115);

(c) Ala-Ala-Met-Lys-Pro-Arg-Thr-Gly-Asp-Gly-Pro-Leu-Glu-Ala-Ala- Lys-Glu-Gly-Arg (SEQ ID NO: 17);

(d) Tyr-Tyr-Trp-Cys-Pro-Gly-Gln-Pro-Phe-Asp-Pro-Ala-Trp-Gly-Pro (SEQ ID NO: 118);

(e) Asp-Ile-Gly-Ser-Glu-Ser-Thr-Glu-Asp-Gln-Gln-Xaa-Ala-Val (SEQ ID NO: 119);

(f) Ala-Glu-Glu-Ser-Ile-Ser-Thr-Xaa-Glu-Xaa-Ile-Val-Pro (SEQ ID NO: 120);

(h) Ala-Pro-Lys-Thr-Tyr-Xaa-Glu-Glu-Leu-Lys-Gly-Thr-Asp-Thr-Gly

Leu-Leu-Asn-Ser-Leu-Ala-Asp-Pro-Asn-Val-Ser-Phe-Ala-Asn (SEQ

ID NO: 123); and (j) Ala-Pro-Glu-Ser-Gly-Ala-Gly-Leu-Gly-Gly-Thr-Val-Gln-Ala-Gly;

(SEQ ID NO: 131) wherein Xaa may be any amino acid.

2. A polypeptide comprising an immunogenic portion of an M. tuberculosis antigen, or a variant of said antigen that differs only in conservative substitutions and/or modifications, wherein said antigen has an N-terminal sequence selected from the group consisting of:

(a) Asp-Pro-Pro-Asp-Pro-His-Gln-Xaa-Asp-Met-Thr-Lys-Gly-Tyr-Tyr- Pro-Gly-Gly-Arg-Arg-Xaa-Phe; (SEQ ID NO: 124) and

(b) Xaa-Tyr-Ile-Ala-Tyr-Xaa-Thr-Thr-Ala-Gly-Ile-Val-Pro-Gly-Lys-Ile- Asn-Val-His-Leu-Val; (SEQ ID NO: 132), wherein Xaa may be any amino acid.

3. A polypeptide comprising an antigenic portion of a soluble M. tuberculosis antigen, or a variant of said antigen that differs only in conservative substitutions and/or modifications, wherein said antigen comprises an amino acid sequence encoded by a DNA sequence selected from the group consisting of the sequences recited in SEQ ID NOS: 1, 2, 4-10, 13-25, 52, 94 and 96, the complements of said sequences, and DNA sequences that hybridize to a sequence recited in SEQ ID NOS: 1, 2, 4-10, 13-25, 52, 94 and 96 or a complement thereof under moderately stringent conditions.

4. A polypeptide comprising an antigenic portion of a M. tuberculosis antigen, or a variant of said antigen that differs only in conservative substitutions and/or modifications, wherein said antigen comprises an amino acid sequence encoded by a DNA sequence selected from the group consisting of the sequences recited in SEQ ID NOS: 26-51, 133, 134, 158-178 and 196, the complements of said sequences, and DNA sequences that hybridize to a sequence recited in SEQ ID NOS: 26-51, 133, 134, 158-178 and 196 or a complement thereof under moderately stringent conditions.

5. A DNA molecule comprising a nucleotide sequence encoding a polypeptide according to any one of claims 1-4.

6. A recombinant expression vector comprising a DNA molecule according to claim 5.

7. A host cell transformed with an expression vector according to claim 6.

8. The host cell of claim 7 wherein the host cell is selected from the group consisting of E. coli, yeast and mammalian cells.

9. A method for detecting M. tuberculosis infection in a biological sample, comprising:

(a) contacting a biological sample with one or more polypeptides according to any of claims 1-4; and

(b) detecting in the sample the presence of antibodies that bind to at least one of the polypeptides, thereby detecting M. tuberculosis infection in the biological sample.

10. A method for detecting M. tuberculosis infection in a biological sample, comprising:

(a) contacting a biological sample with a polypeptide having an N- terminal sequence selected from the group consisting of sequences provided in SEQ ID NO: 129 and 130; and

11. A method for detecting M. tuberculosis infection in a biological sample, comprising:

(a) contacting a biological sample with one or more polypeptides encoded by a DNA sequence selected from the group consisting of SEQ ID NOS: 3, 11, 12, 135, 136, 151-155, 184-188, 194-195 and 198, the complements of said sequences, and DNA sequences that hybridize to a sequence recited in SEQ ID NOS: 3, 11, 12, 135, 136, 151-155, 184-188, 194-195 and 198; and (b) detecting in the sample the presence of antibodies that bind to at least one of the polypeptides, thereby detecting M. tuberculosis infection in the biological sample.

12. The method of any one of claims 9-11 wherein step (a) additionally comprises contacting the biological sample with a 38 kD tuberculosis antigen and step (b) additionally comprises detecting in the sample the presence of antibodies that bind to the 38 kD tuberculosis antigen.

13. The method of any one of claims 9-11 wherein the polypeptide(s) are bound to a solid support.

14. The method of claim 13 wherein the solid support comprises nitrocellulose, latex or a plastic material.

15. The method of any one of claims 9-11 wherein the biological sample is selected from the group consisting of whole blood, serum, plasma, saliva, cerebrospinal fluid and urine.

16. The method of claim 15 wherein the biological sample is whole blood or serum.

17. A method for detecting M. tuberculosis infection in a biological sample, comprising:

(a) contacting the sample with at least two oligonucleotide primers in a polymerase chain reaction, wherein at least one of the oligonucleotide primers is specific for a DNA molecule according to claim 5; and

(b) detecting in the sample a DNA sequence that amplifies in the presence of the oligonucleotide primers, thereby detecting M. tuberculosis infection.

18. The method of claim 17, wherein at least one of the oligonucleotide primers comprises at least about 10 contiguous nucleotides of a DNA molecule according to claim 5.

19. A method for detecting M. tuberculosis infection in a biological sample, comprising:

(a) contacting the sample with at least two oligonucleotide primers in a polymerase chain reaction, wherein at least one of the oligonucleotide primers is specific for a DNA sequence selected from the group consisting of SEQ ID NOS: 3, 11, 12, 135, 136, 151- 155, 184-188, 194-195 and 198; and

(b) detecting in the sample a DNA sequence that amplifies in the presence of the first and second oligonucleotide primers, thereby detecting M. tuberculosis infection.

20. The method of claim 19, wherein at least one of the oligonucleotide primers comprises at least about 10 contiguous nucleotides of a DNA sequence selected from the group consisting of SEQ ID NOS: 3, 11, 12, 135, 136, 151-155, 184-188, 194-195 and 198.

21. The method of claims 17 or 19 wherein the biological sample is selected from the group consisting of whole blood, sputum, serum, plasma, saliva, cerebrospinal fluid and urine.

22. A method for detecting M. tuberculosis infection in a biological sample, comprising:

(a) contacting the sample with one or more oligonucleotide probes specific for a DNA molecule according to claim 5; and

(b) detecting in the sample a DNA sequence that hybridizes to the oligonucleotide probe, thereby detecting M. tuberculosis infection.

23. The method of claim 22 wherein the probe comprises at least about 15 contiguous nucleotides of a DNA molecule according to claim 5.

24. A method for detecting M. tuberculosis infection in a biological sample, comprising:

(a) contacting the sample with one or more oligonucleotide probes specific for a DNA sequence selected from the group consisting of SEQ ID NOS: 3, 11, 12, 135, 136, 151-155, 184-188, 194-195 and 198; and

25. The method of claim 24 wherein the oligonucleotide probe comprises at least about 15 contiguous nucleotides of a DNA sequence selected from the group consisting of SEQ ID NOS: 3, 11, 12, 135, 136, 151-155, 184-188, 194-195 and 198.

26. The method of claims 22 or 24 wherein the biological sample is selected from the group consisting of whole blood, sputum, serum, plasma, saliva, cerebrospinal fluid and urine.

27. A method for detecting M. tuberculosis infection in a biological sample, comprising:

(a) contacting the biological sample with a binding agent which is capable of binding to a polypeptide according to any one of claims 1-4; and

(b) detecting in the sample a protein or polypeptide that binds to the binding agent, thereby detecting M. tuberculosis infection in the biological sample.

28. A method for detecting M. tuberculosis infection in a biological sample, comprising: (a) contacting the biological sample with a binding agent which is capable of binding to a polypeptide having an N-terminal sequence selected from the group consisting of sequences provided in SEQ ID NO: 129 and 130; and

29. A method for detecting M. tuberculosis infection in a biological sample, comprising:

(a) contacting the biological sample with a binding agent which is capable of binding to a polypeptide encoded by a DNA sequence selected from the group consisting of SEQ ID NOS: 3, 11, 12, 135, 136, 151-155, 184-188, 194-195 and 198, the complements of said sequences, and DNA sequences that hybridize to a sequence recited in SEQ ID NOS: 3, 11, 12, 135, 136, 151-155, 184-188, 194-195 and 198; and

30. The method of any one of claims 27-29 wherein the binding agent is a monoclonal antibody.

31. The method of any one of claims 27-29 wherein the binding agent is a polyclonal antibody.

32. A diagnostic kit comprising:

(a) one or more polypeptides according to any of claims 1-4; and

(b) a detection reagent.

33. A diagnostic kit comprising:

(a) one or more polypeptides having an N-terminal sequence selected from the group consisting of sequences provided in SEQ ID NO: 129 and 130; and

(b) a detection reagent.

34. A diagnostic kit comprising:

(a) one or more polypeptides encoded by a DNA sequence selected from the group consisting of SEQ ID NOS: 3, 11, 12, 135, 136, 151-155, 184-188, 194-195 and 198, the complements of said sequences, and DNA sequences that hybridize to a sequence recited in SEQ ID NOS: 3, 11, 12, 135, 136, 151-155, 184-188, 194-195 and 198; and

(b) a detection reagent.

35. The kit of any one of claims 32-34 wherein the polypeptide(s) are immobilized on a solid support.

36. The kit of claim 35 wherein the solid support comprises nitrocellulose, latex or a plastic material.

37. The kit of any one of claims 32-34 wherein the detection reagent comprises a reporter group conjugated to a binding agent.

38. The kit of claim 37 wherein the binding agent is selected from the group consisting of anti-immunoglobulins, Protein G, Protein A and lectins.

39. The kit of claim 37 wherein the reporter group is selected from the group consisting of radioisotopes, fluorescent groups, luminescent groups, enzymes, biotin and dye particles.

40. A diagnostic kit comprising at least two oligonucleotide primers, at least one of the oligonucleotide primers being specific for a DNA molecule according to claim 5.

41. A diagnostic kit according to claim 40, wherein at least one of the oligonucleotide primers comprises at least about 10 contiguous nucleotide of a DNA molecule according to claim 5.

42. A diagnostic kit comprising a at least two oligonucleotide primers, at least one of the primers being specific for a DNA sequence selected from the group consisting of SEQ ID NOS: 3, 11, 12, 135, 136, 151-155, 184-188, 194-195 and 198.

43. A diagnostic kit according to claim 42, wherein at least one of the oligonucleotide primers comprises at least about 10 contiguous nucleotide of a DNA sequence selected from the group consisting of SEQ ID NOS: 3, 11, 12, 135, 136, 151-155, 184-188, 194-195 and 198.

44. A diagnostic kit comprising at least one oligonucleotide probe, the oligonucleotide probe being specific for a DNA molecule according to claim 5.

45. A kit according to claim 44, wherein the oligonucleotide probe comprises at least about 15 contiguous nucleotides of a DNA molecule according to claim 5.

46. A diagnostic kit comprising at least one oligonucleotide probe, the oligonucleotide probe being specific for a DNA sequence selected from the group consisting of SEQ ID NOS: 3, 11, 12, 135, 136, 151-155, 184-188, 194-195 and 198.

47. A kit according to claim 46, wherein the oligonucleotide probe comprises at least about 15 contiguous nucleotides of a DNA sequence selected from the group consisting of SEQ ID NOS: 3, 11, 12, 135, 136, 151-155, 184-188, 194-195 and 198.

48. A monoclonal antibody that binds to a polypeptide according to any of claims 1-4.

49. A polyclonal antibody that binds to a polypeptide according to any of claims 1-4.

50. A fusion protein comprising two or more polypeptides according to any one of claims 1-4.

51. A fusion protein comprising one or more polypeptides according to any one of claims 1-4 and ESAT-6 (SEQ ID NO: 99).

52. A fusion protein comprising a polypeptide having an N-terminal sequence selected from the group of sequences provided in SEQ ID NOS: 129 and 130.

53. A fusion protein comprising one or more polypeptides according to any one of claims 1-4 and the M. tuberculosis antigen 38 kD (SEQ ID NO: 150).

54. A diagnostic kit comprising:

(a) one or more fusion proteins according to any one of claims 50-53; and

(b) a detection reagent.