CN114621329A - T cell epitope peptide compound - Google Patents

T cell epitope peptide compound Download PDF

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CN114621329A
CN114621329A CN202110504310.7A CN202110504310A CN114621329A CN 114621329 A CN114621329 A CN 114621329A CN 202110504310 A CN202110504310 A CN 202110504310A CN 114621329 A CN114621329 A CN 114621329A
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王树毅
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Banju Biotechnology Co ltd
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    • C12N2770/20011—Coronaviridae
    • C12N2770/20034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

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Abstract

The invention provides a T cell epitope peptide complex, which comprises a single peptide or polypeptide consisting of one or more amino acid sequences in SEQ ID NO.4-209 and/or fragments and variants thereof. The T cell epitope peptide compound provided by the invention can be used for preparing a new coronary pneumonia related vaccine and has a good application prospect.

Description

T cell epitope peptide compound
Technical Field
The invention belongs to the field of immunotherapy, and particularly relates to a T cell epitope complex for preventing, diagnosing and treating neocoronary pneumonia and related components thereof.
Background
The T cell epitope refers to an antigen epitope recognized by a T Cell Receptor (TCR), and the epitope component is a polypeptide after protein degradation, mostly exists inside an antigen molecule, and can be recognized by the TCR only by being combined with an MHC molecule to form a complex after being processed by an Antigen Presenting Cell (APC). T cell epitopes include CD8+Epitopes recognized by T cells and CD4+Epitope recognized by T cell, wherein CD8+The epitope recognized by T cell contains 8-10 amino acids, CD4+T cells recognize epitopes that contain 13-17 amino acids.
T cell epitopes can induce cellular immune responses, and as targets for cytotoxic T cell attack, at least one T cell epitope per antigenic molecule is necessary to render the antigen immunogenic. The short peptide sequence on the antigen molecule recognized by the T cell of the antigen molecule is determined, and the positioning of the T cell epitope has important significance for the regulation of specific immune response.
Chinese patent 200710037962.4 discloses a therapeutic cytotoxic T cell epitope vaccine for hepatitis B, which comprises a fusion polypeptide formed by connecting 21 CTL epitopes selected from HBV antigen CTL epitope data with two general T lymphocyte helper epitopes; and Saccharomyces cerevisiae is also selected to express the fusion antigen and is mixed with immunologic adjuvant. The vaccine can activate or enhance the cellular immune response of chronic HBV infected persons, promote the immune elimination of HBV by organisms, and can be used for the immunotherapy of chronic hepatitis B.
Identification of CD4 in novel coronavirus (2019-nCoV) at present+And CD8+The effector T cell epitope has important significance for developing vaccines and medicines for preventing, diagnosing and treating the neocoronary pneumonia.
Disclosure of Invention
In order to solve the above problems, the present invention provides a T cell epitope complex for the prevention, diagnosis and treatment of neocoronary pneumonia.
Unless defined otherwise, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this information disclosure belongs.
AAY: an alanine-tyrosine cleavage motif. An "AAY cleavage motif" refers to a short amino acid motif consisting of the sequence "alanine-tyrosine" that is capable of promoting proteasome-mediated cleavage of a peptide or protein, promoting binding of a transporter associated with antigen processing to a peptide or protein, and/or increasing proteasomal degradation at a specific site within a peptide or protein.
MHC: major histocompatibility complex.
The "T cell epitopes" of the present invention are 7-30 amino acids in length and are capable of specifically binding to Human Leukocyte Antigen (HLA) molecules and interacting with specific T Cell Receptors (TCR). In general, T cell epitopes are linear and do not exhibit specific three-dimensional characteristics. T cell epitopes are not affected by the presence of denaturing solvents. The ability to interact with T-cell epitopes can be predicted by computational methods (De Groot AS et al, (1997), AIDS Res Hum Retroviruses,13(7): 539-41; Schafer JR et al, (1998), Vaccine, 16(19): 1880-4; De Groot AS et al, (2001), Vaccine,19(31): 4385-95; De Groot AR et al, (2003), Vaccine,21(27-30): 4486-.
A "variant" peptide or polypeptide (including a variant T cell epitope) of the invention may differ in amino acid sequence by one or more substitutions, deletions, insertions, inversions, fusions and truncations, or combinations thereof. In certain aspects, variant peptides or polypeptides (including variant T cell epitopes) may differ in amino acid sequence by one or more substitutions, deletions, insertions, inversions, fusions and truncations, or any combination of these variants, so long as the variant retains MHC binding propensity and/or TCR specificity.
In one aspect, the invention provides a T cell epitope peptide complex.
The T cell epitope is a binding epitope of a ligand of an HLA class I and/or HLA class II MHC molecule, and an epitope recognized by a T cell containing the MHC class I and/or class II molecule.
The T cell epitope peptide is selected from a single peptide and/or a polypeptide consisting of one or more amino acid sequences in SEQ ID NO.4-209 and/or fragments and variants thereof.
The variants retain MHC binding propensity and/or TCR specificity. In certain aspects, the mutant can enhance binding to an MHC molecule. In certain aspects, the mutant can enhance binding to a TCR. In certain aspects, the mutation can result in reduced binding to MHC molecules and/or TCRs. In certain aspects, a mutant that binds but does not allow for signal transmission through the TCR is also contemplated.
The variant may comprise an allelic or sequence variant.
The variants may include chemical modifications, e.g., pegylation, glycosylation.
Optionally, 1-12 additional amino acids are included at the N-and/or C-terminus of the sequences SEQ ID NO.4-209 in any proportion. The additional amino acid sequence may be used as an MHC stabilization domain. The use of longer peptides may allow endogenous processing of patient cells and may lead to more efficient antigen presentation and induction of T cell responses.
Wherein the sequences SEQ ID NO.4-8 are derived from the envelope protein (SEQ ID NO.1) of the neocoronaviruse; sequences SEQ ID NO.9-63 are derived from the membrane protein of the new coronavirus (SEQ ID NO. 2); the sequences SEQ ID NO.64-209 are derived from the spike protein of the novel coronavirus (SEQ ID NO. 3).
The T cell epitopes of the invention are highly conserved among known variants of their source proteins, present in more than 10% of the known variants.
What is generally considered to be conservative substitutions are those between the aliphatic amino acids Ala, Val, Leu, Met and Ile; the exchange of hydroxyl residues Ser and Thr, the exchange of acidic residues Asp and Glu, the exchange of amide residues Asn and Gln, the exchange of basic residues His, Lys and Arg and the exchange of aromatic residues Trp, Phe and Tyr.
T cell epitopes of the invention include the epitope EpiMatrixTMAnalyzing the identified at least one putative T cell epitope.
The T cell epitope peptides provided herein are useful in the selective binding and activation of immunogenic T cells. Certain naturally occurring T cells can be activated and/or used to induce immunity to pathogens, such as new coronaviruses.
In certain aspects, the T cell epitopes of the invention bind to at least one common HLA class I and/or class II allele with at least moderate affinity (e.g., IC50 in soluble HLA molecule-based HLA binding assays).
In certain aspects, the peptide or polypeptide may be neutral (uncharged) or in salt form, and may be free of or include modifications such as glycosylation, side chain oxidation, or phosphorylation.
Optionally, the T cell epitope cluster complex further comprises a pharmaceutically acceptable carrier and/or excipient.
Such pharmaceutically acceptable carriers include, but are not limited to, salts having the desired pharmacological activity of the mono-or polypeptide.
Such pharmaceutically acceptable salts include, but are not limited to, the conventional non-toxic salts or the quaternary ammonium salts of the parent compound formed, for example, from non-toxic inorganic or organic acids.
Such conventional non-toxic salts include, but are not limited to, those derived from inorganic and organic acids, stearic acid, glycolic acid, succinic acid, sulfamic acid, sulfoaniline, sulfuric acid, tannins, tartaric acid, toluenesulfonic acid, and common amino acids such as glycine, alanine, phenylalanine, arginine, and the like, selected from 2-acetoxybenzoic acid, 2-isethionic acid, acetic acid, ascorbic acid, benzenesulfonic acid, benzoic acid, bicarbonate, carbonate, citric acid, glycol salts, ethanedisulfonic acid, 1, 2-ethanesulfonic acid, fumaric acid, gluconic acid, glutamic acid, glycolic acid, hexylisophthalic acid.
The T cell epitope complexes of the invention may be administered parenterally, topically, intravenously, orally, subcutaneously, intraarterially, intradermally, transdermally, rectally, intracranially, intrathecally, intraperitoneally, nasally, vaginally, intramuscularly or as an inhalant.
In another aspect, the invention provides a tandem polypeptide.
The tandem polypeptide comprises the T cell epitope peptide.
The tandem polypeptide comprises a single peptide and/or a polypeptide.
Each single peptide or polypeptide of the tandem polypeptide may optionally have one or more linkers, optionally cleavage sensitive sites, adjacent to its N-and/or C-terminus. Such suitable linkers and cleavage sensitive sites include AAY cleavage motifs.
In yet another aspect, the invention provides a chimeric or fusion polypeptide.
The chimeric or fused polypeptide comprises the T cell epitope peptide and/or the tandem polypeptide.
One or more peptides, polypeptides or linker peptides of the invention may be inserted into the heterologous polypeptide, may be added to the C-terminus of the heterologous polypeptide, or may be added to the N-terminus of the heterologous polypeptide.
In certain aspects, the chimeric or fusion polypeptide comprises one or more T cell epitope peptides and/or tandem polypeptides of the invention operably linked to a heterologous polypeptide.
The chimeric or fused polypeptide complex includes one or more peptides, polypeptides and/or linker peptides linked to, linked to (e.g., fused in frame, chemically linked or otherwise associated with) and/or inserted into a heterologous polypeptide.
Preferably, the fusion polypeptide may be a GST fusion polypeptide in which the T cell epitope sequence is fused to the C-terminus of the GST sequence.
Preferably, the fusion polypeptide includes but is not limited to enzymatic fusion polypeptides, such as beta-galactosidase fusion, yeast two-hybrid galactose fusion, polyhistidine fusion.
In yet another aspect, the present invention provides a biological vector.
The biological vector includes but is not limited to recombinant nucleic acid, expression cassette, plasmid, expression vector or recombinant virus, cell.
The biological vector is a nucleic acid molecule, and the nucleic acid encodes the T cell epitope peptide and/or the tandem polypeptide and/or the chimeric or fused polypeptide.
The biological vector is an expression vector or a gene therapy vector or a virus vector.
The expression vector or the gene therapy vector or the virus vector comprises the nucleic acid molecule.
The viral vectors may be derived from different types of viruses, such as swinepox, fowlpox, pseudorabies, Aujezky virus, Salmonella, vaccinia virus, BHV (bovine herpes virus), HVT (herpes virus of Turkey), adenovirus, TGEV (transmissible gastroenteritis coronavirus), erythrovirus and SIV (Simian immunodeficiency virus).
The biological vector is a cell, and the cell comprises the expression vector or the gene therapy vector.
Such cells include, but are not limited to, mammalian cells, bacterial cells, insect cells, or yeast cells.
In yet another aspect, the invention provides an Ii-key hybridization construct.
The Ii-key hybridization construct comprises:
(1) an N-terminal element comprising/consisting essentially of the residues LRMK of SEQ ID No.1 and 0-12 additional sequence residues of SEQ ID No. 1;
(2) an antigenic peptide binding site with MHC class II and/or class I molecules as a C-terminal element;
(3) an optional intermediate chemical structure;
the intermediate chemical structure covalently links hybridized N-terminal and C-terminal elements.
The C-terminal element includes MHC class II and/or class I presented epitopes presented in the form of a polypeptide or peptidomimetic structure that binds to antigenic peptide binding sites of MHC class II and/or class I molecules.
Preferably, said C-terminal element is selected from the group consisting of SEQ ID NO.4-209 and/or fragments and variants thereof.
The random distribution of the C terminal or the N terminal of the SEQ ID NO.4-209 and/or the fragments and variants thereof comprises 0-12 additional amino acids, and the additional amino acids do not influence the MHC binding tendency and TCR specificity of the SEQ ID NO.4-209 and/or the fragments and variants thereof.
In some embodiments, a poly GS linker may be included on the N-terminus of the C-terminal element. The epitope may overlap with the C-terminal element and the linker element. In some cases, there may be additional epitope or determinant overlap between the linker element and the N-terminus. In certain aspects, the intermediate chemical structure may comprise one or more epitopes/determinants, the total length within the defined range being largely determined by the identity and determinants of the epitope/determinant. In certain aspects, the intermediate chemical structure is antigenically neutral and is preferably less than 9 amino acids in length in a linear arrangement, and more preferably 4-6 in length in a linear arrangement.
Preferably, the intermediate chemical structure is selected from an MHC class I epitope or a part thereof and/or a determinant recognized by an antibody or a part thereof.
Preferably, the intermediate chemical structure is a covalently linked group of atoms that, when aligned in a linear fashion, forms a flexible chain extending to a length of 20 amino acids that is also aligned in a linear fashion.
Further, the intermediate chemical structure includes delta-aminopentanoic acid, i.e., 5-aminopentanoic acid (AVA). In certain aspects, the intervening chemical structure may consist of AVA, Ala-Ala, Gly-Gly or other biologically acceptable functional equivalents of AVA, Ala-Ala-Ala and Gly-Gly, preferably Gly-Gly.
The intermediate chemical structure may include chemical groups including, but not limited to, fatty chain moieties interrupted by heteroatoms, such as C2-C6 alkylene or ═ N- (CH2)2-6-N ═.
The intermediate chemical structure may comprise alternating units, for example hydrophobic, lipophilic, aliphatic and arylaliphatic sequences, optionally interrupted by heteroatoms such as O, N or S. The components are preferably selected from the following classes of compounds: sterols, alkyl alcohols, polyglycerol triesters with different alkyl functions, alkylphenols, alkylamines, amides, hydrophobe polyoxyethylenes, and also from the group consisting of hydrophobic polyanhydrides, polyorthoesters, polyphosphazenes, polyhydroxy acids, polycaprolactones, polylactic acids, polyhydroxybutyric acids.
The intermediate compound structure may include repeating short aliphatic chains separated by oxygen atoms, such as polypropylene, isopropene, butylene, isobutylene, pentamethylene, and the like.
Preferably, the Ii-key hybridization construct is selected from the sequence SEQ ID NO. 217-422.
Mammalian Ii-Key peptide LRMKLPKPPKPVSKMR (SEQ ID NO.210) and modified mammalian Ii-Key peptide YRMKLPKPPKPVSKMR (SEQ ID NO.212) are capable of altering the presentation of certain MHC class II restricted antigenic peptides in T lymphocyte hybridomas and thereby recognizing these corresponding antigenic peptides.
All modified Ii-key peptides that retain antigen presentation enhancing activity will function in the enhanced hybrids of the present invention.
Examples of modified versions of the Ii-key peptide known to retain high activity and which may be included in the instant disclosed Ii-key hybridization constructs are LRMK (SEQ ID NO.211), LRMKLPK (SEQ ID NO.213), LRMKLPKS (SEQ ID NO.214), LRMKLPKSAKP (SEQ ID NO.215) and LRMKLPKSAKPVSK (SEQ ID NO. 216). The modified version of the Ii-Key peptide (SEQ ID NO.212) known to retain activity is referred to herein as the "Ii-Key homolog". Thus, the N-terminal element of the Ii-Key hybridization construct may consist of or consist essentially of 4-16 residues of the mammalian Ii-Key peptide SEQ ID No.210 and modifications of the sequence SEQ ID No.210 that retain antigen presentation enhancing activity (which in certain aspects may comprise or consist essentially of residues LRMK of SEQ ID No.210 and 0-12 additional sequence residues of SEQ ID No. 210). Or may otherwise consist essentially of LRMK (SEQ ID NO. 211).
In a further aspect, the invention provides the use of a T cell epitope peptide and/or a tandem polypeptide and/or a chimeric or fusion polypeptide and/or a biological vector and/or an Ii-key hybrid construct as hereinbefore described in the manufacture of a vaccine or medicament.
Such vaccines include, but are not limited to, vaccines for the prevention and/or treatment of new coronavirus infections.
In yet another aspect, the invention provides a vaccine.
Preferably, the vaccine is a vaccine for preventing and/or treating a new coronavirus infection.
The vaccine comprises the T cell epitope peptide and/or the tandem polypeptide and/or the chimeric or fused polypeptide and/or the biological carrier and/or the Ii-key hybridization construct.
In some embodiments, the vaccine further comprises a combination of Live Attenuated Viruses (LAV) or inactivated viruses.
Adjuvants may also be included in the vaccine, including, but not limited to, oil-in-water emulsions, aluminum hydroxide, immunostimulatory complexes, non-ionic block polymers or copolymers, cytokines (e.g., IL-1, IL-2, IL-7, interferon- α, interferon- β, interferon- γ, etc.), saponins, monophosphoryl lipid A, etc.; such adjuvants include, but are not limited to, potassium aluminum sulfate, heat-stable or heat-stable enterotoxin isolated from E.coli, cholera toxin or subunits thereof, diphtheria toxin, tetanus toxin, pertussis toxin, Freund's incomplete or complete adjuvant.
Further, the diphtheria toxin, tetanus toxin and pertussis toxin may be inactivated prior to use by formaldehyde treatment.
The vaccine may also include a freeze-drying stabilizer.
Further, the freeze-drying stabilizer includes, but is not limited to, carbohydrates such as sorbitol, mannitol, starch, sucrose, dextran, or glucose, proteins such as albumin or casein, and derivatives thereof.
The vaccine may also include at least one immunogen from at least one additional pathogen, including but not limited to, porcine actinobacillus pleuropneumoniae, adenovirus, and a virus type a.
The vaccine also comprises pharmaceutically acceptable carriers, excipients, diluents, adjuvants, freeze-drying stabilizers, wetting or emulsifying agents, pH buffering agents, gel or viscosity-increasing additives and preservatives.
Examples of such pharmaceutically acceptable carriers, excipients or diluents include, but are not limited to, demineralized or distilled water, saline solutions, vegetable oils, silicone oils, volatile silicones, mineral oils, lower polyalkylene glycols or lower alkyl glycols, fatty acid esters, polyvinylpyrrolidone, agar, carrageenan, tragacanth, acacia, vaseline.
Further, the vegetable oil includes but is not limited to: peanut oil, safflower oil, olive oil, cottonseed oil, corn oil, sesame oil or coconut oil.
Further, the silicone oil includes but is not limited to: polysiloxanes such as methyl polysiloxane, phenyl polysiloxane and methylphenyl polysiloxane.
Further, the mineral oil includes, but is not limited to: p-hydroxy siloxane.
The lower polyalkylene glycols or lower alkyl glycols include, but are not limited to: polyethylene glycol, polypropylene glycol, ethylene glycol, propylene glycol, 1, 3-butylene glycol, or glycerin.
The fatty acid esters include, but are not limited to: such as isopropyl palmitate, isopropyl myristate or ethyl oleate.
In some embodiments, the vaccine composition may be a liquid formulation, such as an aqueous solution, a water-in-oil or oil-in-water emulsion, a syrup, a medicated wine, or a formulation for parenteral, subcutaneous, intradermal, intramuscular, or intravenous administration, such as a sterile suspension or emulsion. Liquid formulations may also include suspensions and emulsions containing suspending or emulsifying agents. The route of administration may be transdermal, mucosal or parenteral (intradermal, intramuscular, subcutaneous, intravenous or intraperitoneal).
In some embodiments, the vaccine is in the form of a vaccination kit, and the invention also provides a vaccination kit comprising an optionally sterile container comprising an immunologically effective dose of the vaccine, means for injecting the vaccine into an animal, and optionally instructions comprising regulatory information for the immunologically effective dose of the complex for treating and/or preventing the new coronavirus-related disease.
The vaccines of the present application can stimulate, induce and/or amplify the corresponding naturally occurring immune response to the novel coronaviruses, including CD4+And CD8+T cells respond, and in some aspects result in increased secretion of one or more cytokines and chemokines.
In yet another aspect, the present invention provides a medicament.
The medicine comprises the T cell epitope peptide and/or the tandem polypeptide and/or the chimeric or fused polypeptide.
The type of drug includes, but is not limited to, injectable or oral agents.
The oral medicament comprises an inert diluent or an edible carrier.
The oral medicament dosage form comprises but is not limited to capsules, tablets, aerosols, nasal sprays, suppositories, ointments, gels and creams.
The medicines also include but are not limited to: binders, excipients, disintegrating compounds, lubricants, glidants, sweeteners, flavoring agents, penetrants.
The binder includes, but is not limited to, microcrystalline cellulose, baical skullcap root gum or gelatin.
Such excipients include, but are not limited to, starch or lactose.
The disintegrating compound includes, but is not limited to, alginic acid, primrose gum, or corn starch.
The lubricant includes, but is not limited to, magnesium stearate or magnesium stearate.
The slip agent includes, but is not limited to, colloidal silica.
Such sweeteners include, but are not limited to, sucrose or saccharin.
Such flavoring agents include, but are not limited to, peppermint, methyl salicylate, or orange flavoring.
Such penetrants include, but are not limited to, detergents for transmucosal administration, bile salts, and fusidic acid derivatives.
The medicament also comprises other pharmaceutically acceptable carriers, and the pharmaceutically acceptable carriers can be biodegradable and biocompatible polymers, including but not limited to ethylene-vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters and polylactic acid.
Preferably, the pharmaceutically acceptable carrier is a liposome suspension comprising liposomes targeted to infected cells with monoclonal antibodies to viral antigens.
Modes of administration of the drug include, but are not limited to: inhalation, transmucosal or transdermal administration, parenteral (intradermal, intramuscular, subcutaneous, intravenous or intraperitoneal), ocular administration.
The agents may be administered alone or may be administered simultaneously or sequentially with one or more further complexes.
In some embodiments, the drug may also be administered with other agents that enhance passage of the drug across the blood-brain barrier.
In some embodiments, the drug may be implanted in or attached to a biopolymer solid support that allows for slow release of the T cell epitope complex to the desired site.
Detailed Description
The present invention will be further illustrated in detail with reference to the following specific examples, which are not intended to limit the present invention but are merely illustrative thereof. The experimental methods used in the following examples, unless otherwise specified, and experimental methods not specified in specific conditions in the examples, are generally commercially available according to conventional conditions, and materials, reagents, and the like used in the following examples, unless otherwise specified.
Example 1 electronic computer identification of potential epitopes of human leukocyte antigens
T cells specifically recognize epitopes presented by cells in the context of MHC class I and class II molecules. These T cell epitopes can be represented as linear sequences consisting of 7 to 30 contiguous amino acids, suitable for MHC class I or class II binding cleft.
The conserved chain system (EpiVax) is an algorithm for identifying 9-mer polypeptide sequences from a larger data set. The conserved domain system resolves input sequences into 9-mer sequences that are conserved across multiple input complete sequences, e.g., multiple strains of the same pathogen, even for the most variable potential vaccine targets. These 9-mer sequences can be searched in the dataset to find identical matching 9-mer sequences.
The epimatrix hla system (EpiVax) is a set of predictive algorithms encoded in a computer program that can be used to predict class I and class II ligands and T cell epitopes. The epimatrix hla system uses a matrix to mimic the interaction between a particular amino acid and an intramolecular binding site. To identify putative epitopes residing in any given input protein, the appearance matrix system first resolves the input protein into a set of overlapping n-mer frameworks (n-the amino acid length of the epitope polypeptide to be screened; e.g., n-9 or n-10), where each framework overlaps the last by n-1 amino acids. Each frame is then scored according to predicted affinity for one or more common alleles of an HLA molecule. Briefly, for any given n-peptide, the specific amino acid code (one for each of the 20 naturally occurring amino acids) and relative binding positions (1 to n) are used to select coefficients from the prediction matrix. A proprietary approach similar to but not identical to the pocket distribution method first developed by Sturniolo (Sturniolo T et al, 1999, NAT Biotechnol, 17 (6): 555-61) was used to guideThe respective coefficients are given (Sturniolo T et al, 1999, NAT Biotechnol, 17 (6): 555-61). The coefficients are then added to obtain an original score. Then, for EpiMatrix, relative to a fractional distribution derived from a very large set of randomly generated peptide sequencesTMThe raw scores are normalized. The resulting "Z" scores are normally distributed and can be compared directly between alleles. The results indicate that any peptide scoring above 1.64 on the EpiMatrix MHC "Z" scale (approximately the first 5% of any given peptide group) has a great chance and predictability of being scoredTMAnd (4) combining molecules. Peptides scoring above 2.32 on the scale (top 1%) are most likely to bind together.
Polypeptides containing putative T cell epitope clusters are more likely to be positive in vitro and in vivo assays. In certain aspects, a so-called clusttimer is usedTMSecond patented Algorithm further screens the initial phenotype matrixTMThe results of the analysis were analyzed to determine if a putative "cluster" of T cell epitopes was present. ClusTimerTMThe algorithm identifies subregions contained in any given amino acid sequence that contain a statistically abnormal number of putative T cell epitopes. Typical "clusters" of T cell epitopes are between about 9 and 30 amino acids in length and may contain from about 4 to about 40 putative T cell epitopes, given their affinity for multiple alleles and spanning multiple 9-mer frameworks.
Table 1 shows: information related to MHC class II clusters from the envelope (SEQ ID NO.1) of the novel coronavirus, including SEQ ID NO. 4-8; information related to MHC class II clusters from the membrane of the novel coronavirus (SEQ ID NO.2), including SEQ ID NO. 9-63; and information related to MHC class II clusters from the new coronavirus spike (SEQ ID NO.3), including SEQ ID NO. 64-209. The information in the table includes the cluster sequence of the T cell epitope (underlined), the cluster score (no flanking), the number of EpiMatrix hits for MHC class I (the number of hits is the number of EpiMatrix Z scores found in the sequence greater than 1.64 or the first 5%), and the number of EpiMatrix hits for MHC class II (the number of hits is the number of EpiMatrix Z scores found above 1.64 or the first 5%). By adding the fractions of putative T cell epitopes and based on the length of the candidate epitope cluster and the same lengthCalculating the recognition aggregate epitope matrix by subtracting the correction factor from the expected score of the randomly generated clusters of degreesTMEach epitope cluster of the fraction. EpiMatrixTMCluster scores above +10 were considered significant. In certain aspects, the T cell epitopes of the present invention comprise several putative T cell epitopes, forming a pattern referred to as a T cell epitope cluster.
TABLE 1
Figure BDA0003057729410000111
Figure BDA0003057729410000121
Figure BDA0003057729410000131
Figure BDA0003057729410000141
Figure BDA0003057729410000151
Figure BDA0003057729410000161
Figure BDA0003057729410000171
Figure BDA0003057729410000181
Figure BDA0003057729410000191
Figure BDA0003057729410000201
Figure BDA0003057729410000211
Figure BDA0003057729410000221
Figure BDA0003057729410000231
The janus matrix system (EpiVax) was used to screen peptide sequences that were cross-conserved with the host proteome. Janus matrix is an algorithm that predicts the potential for cross-reactivity between a polypeptide cluster and a host genome or proteome based on the conservation of TCR-oriented residues between the polypeptide cluster and the host genome or proteome. The janus matrix algorithm first considers all predicted epitopes contained in a given protein sequence and separates each predicted epitope into its constituent epitopes and epitopes. Each sequence was then screened against the host protein database. Peptides with compatible MHC-facing epitopes (i.e., binding epitopes of the input peptide and its host counterpart are predicted to bind the same MHC allele) and identical TCR-facing epitopes are returned. Homology scores for janus matrix indicate a bias towards immune tolerance. In the case of therapeutic proteins, cross conservation between autologous human epitopes and epitopes in the therapeutic protein may increase the tolerance of the human immune system to such candidate epitopes. In the case of vaccines, cross conservation between human epitopes and antigenic epitopes may suggest that this candidate utilizes immune camouflage to evade immune responses, thereby creating an ineffective vaccine. For example, when the host is human, peptide clusters are screened against the human genome and proteome based on the conservation of TCR-facing residues in their putative HLA ligands. These peptides were then scored using the janus matrix homology score. In certain aspects, peptides with janus matrix homology scores below 2.5 or below 3.0 indicate a lower tolerance potential and may be useful for vaccines. In certain aspects, peptides with janus matrix homology scores above 3.0 indicate high tolerability potential and may not be useful for vaccines, and in certain aspects may be excluded from the T cell epitope complexes of the invention disclosed in this information. Table 1 discloses that the JanusMatrix homology scores for the sequences SEQ ID No.4-209, are all well below 2.5.
The VaccineCAD system is used to rank potential epitope candidate vaccines into strings to avoid the generation of new epitopes when adding vaccine candidate sequences. In particular, the vaccine candidates were designed as tandem bead vaccines by VaccineCAD while minimizing any deleterious epitope junctions that may occur during the addition process. The VaccineCAD may use EpiMatrix to predict binding epitopes.
Table 2 shows a specific Ii-key mixture construct including the sequence SEQ ID NO. 217-422.
TABLE 2
Figure BDA0003057729410000241
Figure BDA0003057729410000251
Figure BDA0003057729410000261
Figure BDA0003057729410000271
Figure BDA0003057729410000281
Figure BDA0003057729410000291
Figure BDA0003057729410000301
Figure BDA0003057729410000311
Example 2 construction of Ii-Key/HER-2Neu antigen hybrid peptide
Immunotherapy against epidermal growth factor receptors that are overexpressed by certain cancer cells can control the growth of these tumors. Her-2/neu is overexpressed on tumors in up to 30% of patients with invasive breast cancer, and this overexpression is associated with a poor clinical prognosis. Women with tumors overexpressing HER2/neu have a poor prognosis despite hormone therapy or chemotherapy, and therefore many tumor vaccines have been developed to target HER-2/neu. The basic principle is that by induction: (1) antigen-specific CD8+And CD4+Lymphocytes; (2) autoantibodies to Her-2/neu that bind to memory B cells; and (3) memory helper T cells, thereby improving therapeutic effects and clinical ease of use.
Compared with cell-based vaccines, DNA vaccines and gene therapy methods, polypeptide vaccines have the following characteristics: (1) easy to construct and manufacture; (2) chemical stabilization; (3) is free of foreign substances and other pathogens; (4) has no carcinogenic potential. The polypeptide vaccine can indeed enhance the CTL cell recognition of MHC class I presented polypeptide immune response, but it would be better if it could enhance helper T cell response by MHC class II presented polypeptide at the same time.
It was found that Her-2/neu polypeptides only produced low level and short CTL responses in the presence of MHC class I only and no MHC class II presented epitopes (Ward R L. hum Immunol.199960: 510-5). Disis et al showed that Her-2/neu polypeptides induced long-term production of Her-2/neu-specific IFN-. gamma. -CD8T cells (Knutson K L.J. Clin invest.2001: 107: 477-84) when both MHC class I and MHC class II presenting epitopes were present. The introduction of the Ii-Key hybrid molecule used in this study into Her-2/neu polypeptides resulted in faster anti-Her-2/neu immune responses at lower and lower doses, and in induction of higher affinity, longer duration T-cell anti-tumor immune responses, leading to better clinical efficacy.
The amino acid sequence of the human Her-2/neu protein (giII 19575768 II) has been obtained from GenBank (SEQ ID NO. 423). An important consideration in selecting polypeptides for cancer immunotherapy is the high degree of sequence homology between Her-2/neu and another member of the growth factor receptor (EGF-r) subclass I family (Lustgarten J. hum Immunol.199752: 109-18). Unlike Her-2/neu, EGF-r is widely expressed in vivo. For two reasons, the peptide sequence identical between Her-2/neu and mouse or human EGF-r was not selected. First, T cell tolerance to such sequences is likely to have been eliminated from high affinity T cells with such epitope specificity. Secondly, it is not desirable to target CTLs to normal cells expressing EGF-gamma peptide. The predicted MHC class II presented epitopes of Her-2/neu protein are shown in Table 3. Table 4 lists the experimentally determined MHC class II restricted epitopes of the human Her-2/neu protein. Table 5 lists Ii-Key/Her-2/neu hybrids designed using some of the MHC class II presenting epitopes of tables 3 and 4. Table 6 lists the predicted MHC class I presenting epitopes of Her-2/neu protein. Table 7 lists the experimentally determined MHC class I presenting Her-2/neu protein epitopes. Table 8 lists the Ii-Key/MHC class II epitope/MHC class I epitope hybrids designed. Table 9 lists the antibody recognition determinants on Her-2/neu. Ii-Key/Her-2/neu hybrids were designed using Table 9 and some of the antibody recognition determinants of MHC class II.
TABLE 3 prediction of MHC class II epitopes of Her-2/neu proteins
Figure BDA0003057729410000331
"position" is the residue position in the primary sequence of the first amino acid in an epitope of an antigen. "sequence" refers to the predicted amino acid sequence of an MHC class II epitope. Scores are reported by the proped program for high score selection with multiple common HLA-DR alleles. Ii-Key is the number of residue positions between the Ii-Key motif and the first residue of the epitope.
TABLE 4 Experimental determination of MHC class II restricted epitopes of human Her-2/neu protein
Figure BDA0003057729410000332
Figure BDA0003057729410000341
Position is the residue position in the primary sequence of the first amino acid in the peptide this sequence is the amino acid sequence of an experimentally determined MHC class II epitope. Ii-Key is the number of residue positions between the Ii-Key motif and the first residue of the epitope. Peptide 5.1 was reported by Perez S. et al (Cancer Immunol Immunother.200250: 615-24). Peptide 5.2 was reported by Sotiriadou R. et al (Br J cancer.200185: 1527-34). Peptide 5.3 was reported by Fisk B.et al (Anticancer Res.199717: 45-53). Peptides 5.8-5.16 were reported in phase I clinical trials by Disis and his colleagues (Disis M.L.J.Clin Oncol 200220: 2624-32). The 5.9 peptide contained the predicted HLA-DRB1-0101 presentation motif LRIVRTGTQL (SEQ ID No.455), and the 5.16 peptide contained the DRB 10101 presentation motif LVSEFSRMA (SEQ ID No.456), both of which stimulated lymphocytes in immunized patients. Other peptides in the series studied by dis et al may be found to contain MHC class II presented motifs when tested against other HLA-DB alleles and have a lower score index. These epitopes may be incorporated into Ii-Key/Her-2 epitope hybrids.
TABLE 5 Ii-Key/Her-2/neu hybrid design
Figure BDA0003057729410000351
"position" in Table 5 refers to the residue position in the primary sequence of the first amino acid in the epitope. "sequence" is the amino acid sequence of a hybrid peptide comprising the MHC class II epitopes of tables 3 and 4.
TABLE 6 prediction of MHC class I epitopes of Her-2/neu proteins
Figure BDA0003057729410000352
Figure BDA0003057729410000361
A "position" is a residue position in the primary sequence of the first amino acid in an epitope of an antigen. "sequence" is the predicted amino acid sequence of an MHC class I epitope. Software programs are used to predict MHC class I presented epitopes. The "fraction" is the dissociation T1/2 of the peptide comprising this subsequence (Tsang KY. J Natl Cancer Inst.199587: 982-90).
TABLE 7 experimentally determined MHC class I representation of epitopes of Her-2/neu proteins
Figure BDA0003057729410000362
A "position" is a residue position in the primary sequence of the first amino acid in an epitope of an antigen. "sequence" is an experimentally defined amino acid sequence of an MHC class I presentation epitope. Peptide 8.1 was presented by HLA-A2.1(Kono K. int J cancer. 199878: 202-8). Peptide 8.2 was presented by HLA-A2.1(Kono K. int J cancer. 199878: 202-8), Rongcun Y., et al (J. Immunol. 1999163: 1037-44). Immunogenicity has also been demonstrated in double transgenic mice expressing HLA-A2.1 and human CD8 (Lustgarten J. hum Immunol.199752: 109-18). Polypeptide 8.3 is HLA-A2.1(Kono, K.int J cancer.199878: 202-8; Rongcun Y.J.Immunol.1999163: 1037-44). In the Lustgarten J. et al study, it was non-immunogenic (Hum Immunol. 199752: 109-18). The three polypeptides 8.4, 8.5 and 8.6 are presented by HLA-A2.1 (Rongcun Y.J.Immunol.1999163: 1037-44). Polypeptide 8.7 was presented by HLA-A2 (Peoples G. ProcNatl AcadSci USA.199592: 432-6) and was non-immunogenic in the Lustgarten J. et al study (Hum Immunol.199752: 109-18). Peptide 8.8 was presented by HLA-A2 (Tanaka Y. int J cancer.200194: 540-4). Polypeptide 8.9 is HLA-A2.1 presentation (Lustgarten J. hum Immunol.52: 109-18). Peptide 8.10 was presented by HLA-A3 (Ka washima I. cancer response.199959: 431-5).
TABLE 8 designed Ii-Key/MHC class II epitope/MHC class I epitope hybrids
Figure BDA0003057729410000371
Position is the residue position in the primary sequence of the first amino acid of the epitope. MHC class I is denoted as I and MHC class II is denoted as II. The sequences are the amino acid sequences of the hybrid peptides in Table 3 that comprise MHC Class II epitopes.
TABLE 9 antibody recognition determinants on Her-2/neu
Figure BDA0003057729410000372
These peptides were reported to react with sera from mice immunized with GST fusion proteins containing Her-2/neu (C220-C235) sequences (YIp YL. cancer Immunol Immunol.200250: 569-87; YIp Y L.J.Immunol.2001166: 5271-8).
Ii-Key/Her-2/neu hybrids were designed using some of the antibody recognition determinants in Table 9 and MHC class II to present the epitopes of tables 3 and 4. As shown in table 10.
Watch 10
Figure BDA0003057729410000381
"position" in Table 10 refers to the residue position in the first amino acid sequence of the first amino acid in an MHC class II epitope, after the accession number, of the first residue in the reported antibody recognition epitope-containing polypeptide. "sequence" refers to the amino acids of a hybrid peptide.
Sequence listing
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Met Tyr Ser Phe Val Ser Glu Glu Thr Gly Thr Leu Ile Val Asn Ser
1 5 10 15
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20 25 30
Ile Leu Thr Ala Leu Arg Leu Cys Ala Tyr Cys Cys Asn Ile Val Asn
35 40 45
Val Ser Leu Val Lys Pro Ser Phe Tyr Val Tyr Ser Arg Val Lys Asn
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Leu Asn Ser Ser Arg Val Pro Asp Leu Leu Val
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Cys Leu Leu Gln Phe Ala Tyr Ala Asn Arg Asn Arg Phe Leu Tyr Ile
35 40 45
Ile Lys Leu Ile Phe Leu Trp Leu Leu Trp Pro Val Thr Leu Ala Cys
50 55 60
Phe Val Leu Ala Ala Val Tyr Arg Ile Asn Trp Ile Thr Gly Gly Ile
65 70 75 80
Ala Ile Ala Met Ala Cys Leu Val Gly Leu Met Trp Leu Ser Tyr Phe
85 90 95
Ile Ala Ser Phe Arg Leu Phe Ala Arg Thr Arg Ser Met Trp Ser Phe
100 105 110
Asn Pro Glu Thr Asn Ile Leu Leu Asn Val Pro Leu His Gly Thr Ile
115 120 125
Leu Thr Arg Pro Leu Leu Glu Ser Glu Leu Val Ile Gly Ala Val Ile
130 135 140
Leu Arg Gly His Leu Arg Ile Ala Gly His His Leu Gly Arg Cys Asp
145 150 155 160
Ile Lys Asp Leu Pro Lys Glu Ile Thr Val Ala Thr Ser Arg Thr Leu
165 170 175
Ser Tyr Tyr Lys Leu Gly Ala Ser Gln Arg Val Ala Gly Asp Ser Gly
180 185 190
Phe Ala Ala Tyr Ser Arg Tyr Arg Ile Gly Asn Tyr Lys Leu Asn Thr
195 200 205
Asp His Ser Ser Ser Ser Asp Asn Ile Ala Leu Leu Val Gln
210 215 220
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Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val
1 5 10 15
Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe
20 25 30
Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu
35 40 45
His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp
50 55 60
Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp
65 70 75 80
Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu
85 90 95
Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser
100 105 110
Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile
115 120 125
Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr
130 135 140
Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr
145 150 155 160
Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu
165 170 175
Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe
180 185 190
Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr
195 200 205
Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu
210 215 220
Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr
225 230 235 240
Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser
245 250 255
Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro
260 265 270
Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala
275 280 285
Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys
290 295 300
Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val
305 310 315 320
Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys
325 330 335
Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala
340 345 350
Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu
355 360 365
Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro
370 375 380
Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe
385 390 395 400
Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly
405 410 415
Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys
420 425 430
Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn
435 440 445
Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe
450 455 460
Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys
465 470 475 480
Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly
485 490 495
Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val
500 505 510
Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys
515 520 525
Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn
530 535 540
Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu
545 550 555 560
Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val
565 570 575
Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe
580 585 590
Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val
595 600 605
Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile
610 615 620
His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser
625 630 635 640
Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val
645 650 655
Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala
660 665 670
Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala
675 680 685
Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser
690 695 700
Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile
705 710 715 720
Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val
725 730 735
Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu
740 745 750
Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr
755 760 765
Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln
770 775 780
Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe
785 790 795 800
Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser
805 810 815
Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly
820 825 830
Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp
835 840 845
Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu
850 855 860
Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly
865 870 875 880
Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile
885 890 895
Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr
900 905 910
Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn
915 920 925
Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala
930 935 940
Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn
945 950 955 960
Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val
965 970 975
Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln
980 985 990
Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val
995 1000 1005
Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu
1010 1015 1020
Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val
1025 1030 1035 1040
Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala
1045 1050 1055
Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu
1060 1065 1070
Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His
1075 1080 1085
Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val
1090 1095 1100
Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr
1105 1110 1115 1120
Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr
1125 1130 1135
Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu
1140 1145 1150
Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp
1155 1160 1165
Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp
1170 1175 1180
Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu
1185 1190 1195 1200
Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile
1205 1210 1215
Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile
1220 1225 1230
Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys
1235 1240 1245
Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val
1250 1255 1260
Leu Lys Gly Val Lys Leu His Tyr Thr
1265 1270
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Pro Ser Phe Tyr Val Tyr Ser Arg Val Lys Asn Leu Asn Ser Ser Arg
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Tyr Val Tyr Ser Arg Val Lys Asn Leu Asn Ser Ser Arg
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Tyr Val Tyr Ser Arg Val Lys Asn Leu Asn Ser
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Lys Lys Leu Leu Glu Gln Trp Asn Leu Val Ile Gly Phe Leu
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Leu Leu Glu Gln Trp Asn Leu Val Ile Gly Phe Leu
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Glu Gln Trp Asn Leu Val Ile Gly Phe Leu Phe Leu Thr Trp
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Gln Trp Asn Leu Val Ile Gly Phe Leu Phe Leu Thr Trp
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Trp Asn Leu Val Ile Gly Phe Leu Phe Leu Thr Trp
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Trp Asn Leu Val Ile Gly Phe Leu Phe
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Cys Leu Leu Gln Phe Ala Tyr Ala Asn Arg Asn Arg Phe Leu Tyr Ile
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<400> 21
Leu Leu Gln Phe Ala Tyr Ala Asn Arg Asn Arg Phe Leu Tyr Ile
1 5 10 15
<210> 22
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 22
Leu Gln Phe Ala Tyr Ala Asn Arg Asn Arg Phe Leu Tyr Ile
1 5 10
<210> 23
<211> 11
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 23
Leu Gln Phe Ala Tyr Ala Asn Arg Asn Arg Phe
1 5 10
<210> 24
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 24
Arg Asn Arg Phe Leu Tyr Ile Ile Lys Leu Ile Phe Leu Trp Leu Leu
1 5 10 15
Trp Pro Val
<210> 25
<211> 18
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 25
Asn Arg Phe Leu Tyr Ile Ile Lys Leu Ile Phe Leu Trp Leu Leu Trp
1 5 10 15
Pro Val
<210> 26
<211> 17
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 26
Arg Phe Leu Tyr Ile Ile Lys Leu Ile Phe Leu Trp Leu Leu Trp Pro
1 5 10 15
Val
<210> 27
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 27
Phe Leu Tyr Ile Ile Lys Leu Ile Phe Leu Trp Leu Leu Trp Pro Val
1 5 10 15
<210> 28
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 28
Phe Leu Tyr Ile Ile Lys Leu Ile Phe Leu Trp Leu Leu
1 5 10
<210> 29
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 29
Leu Ala Cys Phe Val Leu Ala Ala Val Tyr Arg Ile Asn Trp Ile
1 5 10 15
<210> 30
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 30
Ala Cys Phe Val Leu Ala Ala Val Tyr Arg Ile Asn Trp Ile
1 5 10
<210> 31
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 31
Cys Phe Val Leu Ala Ala Val Tyr Arg Ile Asn Trp Ile
1 5 10
<210> 32
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 32
Phe Val Leu Ala Ala Val Tyr Arg Ile Asn Trp Ile
1 5 10
<210> 33
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 33
Phe Val Leu Ala Ala Val Tyr Arg Ile
1 5
<210> 34
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 34
Leu Ser Tyr Phe Ile Ala Ser Phe Arg Leu Phe Ala Arg Thr Arg
1 5 10 15
<210> 35
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 35
Ser Tyr Phe Ile Ala Ser Phe Arg Leu Phe Ala Arg Thr Arg
1 5 10
<210> 36
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 36
Tyr Phe Ile Ala Ser Phe Arg Leu Phe Ala Arg Thr Arg
1 5 10
<210> 37
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 37
Phe Ile Ala Ser Phe Arg Leu Phe Ala Arg Thr Arg
1 5 10
<210> 38
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 38
Phe Ile Ala Ser Phe Arg Leu Phe Ala
1 5
<210> 39
<211> 18
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 39
Ile Ala Ser Phe Arg Leu Phe Ala Arg Thr Arg Ser Met Trp Ser Phe
1 5 10 15
Asn Pro
<210> 40
<211> 17
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 40
Ala Ser Phe Arg Leu Phe Ala Arg Thr Arg Ser Met Trp Ser Phe Asn
1 5 10 15
Pro
<210> 41
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 41
Ser Phe Arg Leu Phe Ala Arg Thr Arg Ser Met Trp Ser Phe Asn Pro
1 5 10 15
<210> 42
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 42
Phe Arg Leu Phe Ala Arg Thr Arg Ser Met Trp Ser Phe Asn Pro
1 5 10 15
<210> 43
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 43
Phe Arg Leu Phe Ala Arg Thr Arg Ser Met Trp Ser
1 5 10
<210> 44
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 44
Arg Gly His Leu Arg Ile Ala Gly His His Leu Gly Arg Cys Asp
1 5 10 15
<210> 45
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 45
Gly His Leu Arg Ile Ala Gly His His Leu Gly Arg Cys Asp
1 5 10
<210> 46
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 46
His Leu Arg Ile Ala Gly His His Leu Gly Arg Cys Asp
1 5 10
<210> 47
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 47
Leu Arg Ile Ala Gly His His Leu Gly Arg Cys Asp
1 5 10
<210> 48
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 48
Leu Arg Ile Ala Gly His His Leu Gly
1 5
<210> 49
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 49
Pro Lys Glu Ile Thr Val Ala Thr Ser Arg Thr Leu Ser Tyr Tyr
1 5 10 15
<210> 50
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 50
Lys Glu Ile Thr Val Ala Thr Ser Arg Thr Leu Ser Tyr Tyr
1 5 10
<210> 51
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 51
Glu Ile Thr Val Ala Thr Ser Arg Thr Leu Ser Tyr Tyr
1 5 10
<210> 52
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 52
Ile Thr Val Ala Thr Ser Arg Thr Leu Ser Tyr Tyr
1 5 10
<210> 53
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 53
Ile Thr Val Ala Thr Ser Arg Thr Leu
1 5
<210> 54
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 54
Thr Leu Ser Tyr Tyr Lys Leu Gly Ala Ser Gln Arg Val Ala Gly Asp
1 5 10 15
<210> 55
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 55
Thr Leu Ser Tyr Tyr Lys Leu Gly Ala Ser Gln Arg Val Ala Gly Asp
1 5 10 15
<210> 56
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 56
Thr Leu Ser Tyr Tyr Lys Leu Gly Ala Ser Gln Arg Val Ala Gly Asp
1 5 10 15
<210> 57
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 57
Thr Leu Ser Tyr Tyr Lys Leu Gly Ala Ser Gln Arg Val Ala Gly Asp
1 5 10 15
<210> 58
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 58
Thr Leu Ser Tyr Tyr Lys Leu Gly Ala Ser Gln Arg Val Ala Gly Asp
1 5 10 15
<210> 59
<211> 17
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 59
Ile Gly Asn Tyr Lys Leu Asn Thr Asp His Ser Ser Ser Ser Asp Asn
1 5 10 15
Ile
<210> 60
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 60
Gly Asn Tyr Lys Leu Asn Thr Asp His Ser Ser Ser Ser Asp Asn Ile
1 5 10 15
<210> 61
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 61
Asn Tyr Lys Leu Asn Thr Asp His Ser Ser Ser Ser Asp Asn Ile
1 5 10 15
<210> 62
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 62
Tyr Lys Leu Asn Thr Asp His Ser Ser Ser Ser Asp Asn Ile
1 5 10
<210> 63
<211> 11
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 63
Tyr Lys Leu Asn Thr Asp His Ser Ser Ser Ser
1 5 10
<210> 64
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 64
Pro Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro
1 5 10 15
<210> 65
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 65
Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro
1 5 10
<210> 66
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 66
Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro
1 5 10
<210> 67
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 67
Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro
1 5 10
<210> 68
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 68
Tyr Thr Asn Ser Phe Thr Arg Gly Val
1 5
<210> 69
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 69
Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp Phe His
1 5 10 15
<210> 70
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 70
Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp Phe His
1 5 10
<210> 71
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 71
Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp Phe His
1 5 10
<210> 72
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 72
Phe Leu Pro Phe Phe Ser Asn Val Thr Trp Phe His
1 5 10
<210> 73
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 73
Phe Leu Pro Phe Phe Ser Asn Val Thr
1 5
<210> 74
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 74
Asn Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr
1 5 10 15
<210> 75
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 75
Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr
1 5 10 15
<210> 76
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 76
Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr
1 5 10
<210> 77
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 77
Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr
1 5 10
<210> 78
<211> 10
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 78
Trp Phe His Ala Ile His Val Ser Gly Thr
1 5 10
<210> 79
<211> 17
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 79
Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg
1 5 10 15
Gly
<210> 80
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 80
Asp Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly
1 5 10 15
<210> 81
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 81
Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly
1 5 10 15
<210> 82
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 82
Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly
1 5 10
<210> 83
<211> 11
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 83
Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile
1 5 10
<210> 84
<211> 17
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 84
Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile Lys
1 5 10 15
Val
<210> 85
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 85
Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile Lys Val
1 5 10 15
<210> 86
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 86
Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile Lys Val
1 5 10 15
<210> 87
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 87
Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile Lys Val
1 5 10
<210> 88
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 88
Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile
1 5 10
<210> 89
<211> 17
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 89
Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser
1 5 10 15
Glu
<210> 90
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 90
Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu
1 5 10 15
<210> 91
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 91
Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu
1 5 10 15
<210> 92
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 92
Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu
1 5 10
<210> 93
<211> 11
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 93
Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met
1 5 10
<210> 94
<211> 18
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 94
Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu
1 5 10 15
Tyr Val
<210> 95
<211> 17
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 95
Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr
1 5 10 15
Val
<210> 96
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 96
Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val
1 5 10 15
<210> 97
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 97
Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val
1 5 10 15
<210> 98
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 98
Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe
1 5 10
<210> 99
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 99
Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu
1 5 10 15
<210> 100
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 100
Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu
1 5 10
<210> 101
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 101
Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu
1 5 10
<210> 102
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 102
Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu
1 5 10
<210> 103
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 103
Phe Lys Ile Tyr Ser Lys His Thr Pro
1 5
<210> 104
<211> 17
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 104
Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp
1 5 10 15
Ala
<210> 105
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 105
Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala
1 5 10 15
<210> 106
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 106
Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala
1 5 10 15
<210> 107
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 107
Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala
1 5 10
<210> 108
<211> 11
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 108
Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile
1 5 10
<210> 109
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 109
Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe
1 5 10 15
<210> 110
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 110
Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe
1 5 10
<210> 111
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 111
Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe
1 5 10
<210> 112
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 112
Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe
1 5 10
<210> 113
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 113
Phe Arg Val Gln Pro Thr Glu Ser Ile
1 5
<210> 114
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 114
Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala
1 5 10 15
<210> 115
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 115
Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala
1 5 10
<210> 116
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 116
Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala
1 5 10
<210> 117
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 117
Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala
1 5 10
<210> 118
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 118
Val Phe Asn Ala Thr Arg Phe Ala Ser
1 5
<210> 119
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 119
Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn
1 5 10
<210> 120
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 120
Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn
1 5 10
<210> 121
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 121
Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn
1 5 10
<210> 122
<211> 11
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 122
Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn
1 5 10
<210> 123
<211> 10
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 123
Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser
1 5 10
<210> 124
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 124
Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr
1 5 10 15
<210> 125
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 125
Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr
1 5 10
<210> 126
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 126
Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr
1 5 10
<210> 127
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 127
Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr
1 5 10
<210> 128
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 128
Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn
1 5 10 15
<210> 129
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 129
Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn
1 5 10
<210> 130
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 130
Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn
1 5 10
<210> 131
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 131
Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn
1 5 10
<210> 132
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 132
Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg
1 5
<210> 133
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 133
Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe
1 5 10 15
<210> 134
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 134
Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe
1 5 10
<210> 135
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 135
Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe
1 5 10
<210> 136
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 136
Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe
1 5 10
<210> 137
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 137
Tyr Arg Leu Phe Arg Lys Ser Asn Leu
1 5
<210> 138
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 138
Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp
1 5 10
<210> 139
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 139
Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp
1 5 10
<210> 140
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 140
Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp
1 5 10
<210> 141
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 141
Phe Arg Lys Ser Asn Leu Lys Pro Phe
1 5
<210> 142
<211> 18
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 142
Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln
1 5 10 15
Pro Thr
<210> 143
<211> 17
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 143
Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro
1 5 10 15
Thr
<210> 144
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 144
Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr
1 5 10 15
<210> 145
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 145
Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr
1 5 10 15
<210> 146
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 146
Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe
1 5 10
<210> 147
<211> 17
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 147
Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro
1 5 10 15
Tyr
<210> 148
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 148
Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr
1 5 10 15
<210> 149
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 149
Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr
1 5 10 15
<210> 150
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 150
Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr
1 5 10
<210> 151
<211> 11
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 151
Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr
1 5 10
<210> 152
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 152
Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly
1 5 10 15
<210> 153
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 153
Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly
1 5 10
<210> 154
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 154
Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly
1 5 10
<210> 155
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 155
Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly
1 5 10
<210> 156
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 156
Phe Glu Leu Leu His Ala Pro Ala Thr
1 5
<210> 157
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 157
Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly
1 5 10 15
<210> 158
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 158
Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly
1 5 10
<210> 159
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 159
Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly
1 5 10
<210> 160
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 160
Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly
1 5 10
<210> 161
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 161
Val Asn Phe Asn Phe Asn Gly Leu Thr
1 5
<210> 162
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 162
Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu
1 5 10 15
<210> 163
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 163
Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu
1 5 10
<210> 164
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 164
Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu
1 5 10
<210> 165
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 165
Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu
1 5 10
<210> 166
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 166
Phe Asn Gly Leu Thr Gly Thr Gly Val
1 5
<210> 167
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 167
Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln
1 5 10
<210> 168
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 168
Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln
1 5 10
<210> 169
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 169
Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln
1 5 10
<210> 170
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 170
Leu Asn Arg Ala Leu Thr Gly Ile Ala
1 5
<210> 171
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 171
Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly
1 5 10 15
<210> 172
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 172
Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly
1 5 10
<210> 173
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 173
Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly
1 5 10
<210> 174
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 174
Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly
1 5 10
<210> 175
<211> 10
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 175
Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu
1 5 10
<210> 176
<211> 17
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 176
Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly
1 5 10 15
Val
<210> 177
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 177
Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val
1 5 10 15
<210> 178
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 178
Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val
1 5 10 15
<210> 179
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 179
Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val
1 5 10
<210> 180
<211> 11
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 180
Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly
1 5 10
<210> 181
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 181
Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile
1 5 10 15
<210> 182
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 182
Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile
1 5 10
<210> 183
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 183
Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile
1 5 10
<210> 184
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 184
Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile
1 5 10
<210> 185
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 185
Ile Ala Asn Gln Phe Asn Ser Ala Ile
1 5
<210> 186
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 186
Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu
1 5 10 15
<210> 187
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 187
Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu
1 5 10
<210> 188
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 188
Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu
1 5 10
<210> 189
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 189
Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu
1 5 10
<210> 190
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 190
Phe Asn Ser Ala Ile Gly Lys Ile Gln
1 5
<210> 191
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 191
Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu
1 5 10 15
<210> 192
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 192
Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu
1 5 10
<210> 193
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 193
Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu
1 5 10
<210> 194
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 194
Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu
1 5 10
<210> 195
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 195
Leu Gln Ser Leu Gln Thr Tyr Val Thr
1 5
<210> 196
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 196
Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro His
1 5 10 15
<210> 197
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 197
Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro His
1 5 10
<210> 198
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 198
Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro His
1 5 10
<210> 199
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 199
Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro His
1 5 10
<210> 200
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 200
Tyr His Leu Met Ser Phe Pro Gln Ser
1 5
<210> 201
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 201
Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu
1 5 10 15
<210> 202
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 202
Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu
1 5 10
<210> 203
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 203
Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu
1 5 10
<210> 204
<211> 10
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 204
Val Ile Gly Ile Val Asn Asn Thr Val Tyr
1 5 10
<210> 205
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 205
Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly
1 5 10 15
<210> 206
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 206
Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly
1 5 10 15
<210> 207
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 207
Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly
1 5 10
<210> 208
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 208
Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly
1 5 10
<210> 209
<211> 10
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 209
Tyr Phe Lys Asn His Thr Ser Pro Asp Val
1 5 10
<210> 210
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 210
Leu Arg Met Lys Leu Pro Lys Pro Pro Lys Pro Val Ser Lys Met Arg
1 5 10 15
<210> 211
<211> 4
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 211
Leu Arg Met Lys
1
<210> 212
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 212
Tyr Arg Met Lys Leu Pro Lys Pro Pro Lys Pro Val Ser Lys Met Arg
1 5 10 15
<210> 213
<211> 7
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 213
Leu Arg Met Lys Leu Pro Lys
1 5
<210> 214
<211> 8
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 214
Leu Arg Met Lys Leu Pro Lys Ser
1 5
<210> 215
<211> 11
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 215
Leu Arg Met Lys Leu Pro Lys Ser Ala Lys Pro
1 5 10
<210> 216
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 216
Leu Arg Met Lys Leu Pro Lys Ser Ala Lys Pro Val Ser Lys
1 5 10
<210> 217
<211> 23
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 217
Leu Arg Met Lys Ala Val Ala Pro Ser Phe Tyr Val Tyr Ser Arg Val
1 5 10 15
Lys Asn Leu Asn Ser Ser Arg
20
<210> 218
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 218
Leu Arg Met Lys Ala Val Ala Ser Phe Tyr Val Tyr Ser Arg Val Lys
1 5 10 15
Asn Leu Asn Ser Ser Arg
20
<210> 219
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 219
Leu Arg Met Lys Ala Val Ala Phe Tyr Val Tyr Ser Arg Val Lys Asn
1 5 10 15
Leu Asn Ser Ser Arg
20
<210> 220
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 220
Leu Arg Met Lys Ala Val Ala Tyr Val Tyr Ser Arg Val Lys Asn Leu
1 5 10 15
Asn Ser Ser Arg
20
<210> 221
<211> 18
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 221
Leu Arg Met Lys Ala Val Ala Tyr Val Tyr Ser Arg Val Lys Asn Leu
1 5 10 15
Asn Ser
<210> 222
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 222
Leu Arg Met Lys Ala Val Ala Leu Lys Lys Leu Leu Glu Gln Trp Asn
1 5 10 15
Leu Val Ile Gly Phe Leu
20
<210> 223
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 223
Leu Arg Met Lys Ala Val Ala Lys Lys Leu Leu Glu Gln Trp Asn Leu
1 5 10 15
Val Ile Gly Phe Leu
20
<210> 224
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 224
Leu Arg Met Lys Ala Val Ala Lys Leu Leu Glu Gln Trp Asn Leu Val
1 5 10 15
Ile Gly Phe Leu
20
<210> 225
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 225
Leu Arg Met Lys Ala Val Ala Leu Leu Glu Gln Trp Asn Leu Val Ile
1 5 10 15
Gly Phe Leu
<210> 226
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 226
Leu Arg Met Lys Ala Val Ala Leu Leu Glu Gln Trp Asn Leu Val Ile
1 5 10 15
<210> 227
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 227
Leu Arg Met Lys Ala Val Ala Leu Glu Gln Trp Asn Leu Val Ile Gly
1 5 10 15
Phe Leu Phe Leu Thr Trp
20
<210> 228
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 228
Leu Arg Met Lys Ala Val Ala Glu Gln Trp Asn Leu Val Ile Gly Phe
1 5 10 15
Leu Phe Leu Thr Trp
20
<210> 229
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 229
Leu Arg Met Lys Ala Val Ala Gln Trp Asn Leu Val Ile Gly Phe Leu
1 5 10 15
Phe Leu Thr Trp
20
<210> 230
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 230
Leu Arg Met Lys Ala Val Ala Trp Asn Leu Val Ile Gly Phe Leu Phe
1 5 10 15
Leu Thr Trp
<210> 231
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 231
Leu Arg Met Lys Ala Val Ala Trp Asn Leu Val Ile Gly Phe Leu Phe
1 5 10 15
<210> 232
<211> 24
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 232
Leu Arg Met Lys Ala Val Ala Ile Cys Leu Leu Gln Phe Ala Tyr Ala
1 5 10 15
Asn Arg Asn Arg Phe Leu Tyr Ile
20
<210> 233
<211> 23
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 233
Leu Arg Met Lys Ala Val Ala Cys Leu Leu Gln Phe Ala Tyr Ala Asn
1 5 10 15
Arg Asn Arg Phe Leu Tyr Ile
20
<210> 234
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 234
Leu Arg Met Lys Ala Val Ala Leu Leu Gln Phe Ala Tyr Ala Asn Arg
1 5 10 15
Asn Arg Phe Leu Tyr Ile
20
<210> 235
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 235
Leu Arg Met Lys Ala Val Ala Leu Gln Phe Ala Tyr Ala Asn Arg Asn
1 5 10 15
Arg Phe Leu Tyr Ile
20
<210> 236
<211> 18
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 236
Leu Arg Met Lys Ala Val Ala Leu Gln Phe Ala Tyr Ala Asn Arg Asn
1 5 10 15
Arg Phe
<210> 237
<211> 26
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 237
Leu Arg Met Lys Ala Val Ala Arg Asn Arg Phe Leu Tyr Ile Ile Lys
1 5 10 15
Leu Ile Phe Leu Trp Leu Leu Trp Pro Val
20 25
<210> 238
<211> 25
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 238
Leu Arg Met Lys Ala Val Ala Asn Arg Phe Leu Tyr Ile Ile Lys Leu
1 5 10 15
Ile Phe Leu Trp Leu Leu Trp Pro Val
20 25
<210> 239
<211> 24
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 239
Leu Arg Met Lys Ala Val Ala Arg Phe Leu Tyr Ile Ile Lys Leu Ile
1 5 10 15
Phe Leu Trp Leu Leu Trp Pro Val
20
<210> 240
<211> 23
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 240
Leu Arg Met Lys Ala Val Ala Phe Leu Tyr Ile Ile Lys Leu Ile Phe
1 5 10 15
Leu Trp Leu Leu Trp Pro Val
20
<210> 241
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 241
Leu Arg Met Lys Ala Val Ala Phe Leu Tyr Ile Ile Lys Leu Ile Phe
1 5 10 15
Leu Trp Leu Leu
20
<210> 242
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 242
Leu Arg Met Lys Ala Val Ala Leu Ala Cys Phe Val Leu Ala Ala Val
1 5 10 15
Tyr Arg Ile Asn Trp Ile
20
<210> 243
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 243
Leu Arg Met Lys Ala Val Ala Ala Cys Phe Val Leu Ala Ala Val Tyr
1 5 10 15
Arg Ile Asn Trp Ile
20
<210> 244
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 244
Leu Arg Met Lys Ala Val Ala Cys Phe Val Leu Ala Ala Val Tyr Arg
1 5 10 15
Ile Asn Trp Ile
20
<210> 245
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 245
Leu Arg Met Lys Ala Val Ala Phe Val Leu Ala Ala Val Tyr Arg Ile
1 5 10 15
Asn Trp Ile
<210> 246
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 246
Leu Arg Met Lys Ala Val Ala Phe Val Leu Ala Ala Val Tyr Arg Ile
1 5 10 15
<210> 247
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 247
Leu Arg Met Lys Ala Val Ala Leu Ser Tyr Phe Ile Ala Ser Phe Arg
1 5 10 15
Leu Phe Ala Arg Thr Arg
20
<210> 248
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 248
Leu Arg Met Lys Ala Val Ala Ser Tyr Phe Ile Ala Ser Phe Arg Leu
1 5 10 15
Phe Ala Arg Thr Arg
20
<210> 249
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 249
Leu Arg Met Lys Ala Val Ala Tyr Phe Ile Ala Ser Phe Arg Leu Phe
1 5 10 15
Ala Arg Thr Arg
20
<210> 250
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 250
Leu Arg Met Lys Ala Val Ala Phe Ile Ala Ser Phe Arg Leu Phe Ala
1 5 10 15
Arg Thr Arg
<210> 251
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 251
Leu Arg Met Lys Ala Val Ala Phe Ile Ala Ser Phe Arg Leu Phe Ala
1 5 10 15
<210> 252
<211> 25
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 252
Leu Arg Met Lys Ala Val Ala Ile Ala Ser Phe Arg Leu Phe Ala Arg
1 5 10 15
Thr Arg Ser Met Trp Ser Phe Asn Pro
20 25
<210> 253
<211> 24
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 253
Leu Arg Met Lys Ala Val Ala Ala Ser Phe Arg Leu Phe Ala Arg Thr
1 5 10 15
Arg Ser Met Trp Ser Phe Asn Pro
20
<210> 254
<211> 23
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 254
Leu Arg Met Lys Ala Val Ala Ser Phe Arg Leu Phe Ala Arg Thr Arg
1 5 10 15
Ser Met Trp Ser Phe Asn Pro
20
<210> 255
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 255
Leu Arg Met Lys Ala Val Ala Phe Arg Leu Phe Ala Arg Thr Arg Ser
1 5 10 15
Met Trp Ser Phe Asn Pro
20
<210> 256
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 256
Leu Arg Met Lys Ala Val Ala Phe Arg Leu Phe Ala Arg Thr Arg Ser
1 5 10 15
Met Trp Ser
<210> 257
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 257
Leu Arg Met Lys Ala Val Ala Arg Gly His Leu Arg Ile Ala Gly His
1 5 10 15
His Leu Gly Arg Cys Asp
20
<210> 258
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 258
Leu Arg Met Lys Ala Val Ala Gly His Leu Arg Ile Ala Gly His His
1 5 10 15
Leu Gly Arg Cys Asp
20
<210> 259
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 259
Leu Arg Met Lys Ala Val Ala His Leu Arg Ile Ala Gly His His Leu
1 5 10 15
Gly Arg Cys Asp
20
<210> 260
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 260
Leu Arg Met Lys Ala Val Ala Leu Arg Ile Ala Gly His His Leu Gly
1 5 10 15
Arg Cys Asp
<210> 262
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 262
Leu Arg Met Lys Ala Val Ala Leu Arg Ile Ala Gly His His Leu Gly
1 5 10 15
<210> 262
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 262
Leu Arg Met Lys Ala Val Ala Pro Lys Glu Ile Thr Val Ala Thr Ser
1 5 10 15
Arg Thr Leu Ser Tyr Tyr
20
<210> 263
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 263
Leu Arg Met Lys Ala Val Ala Lys Glu Ile Thr Val Ala Thr Ser Arg
1 5 10 15
Thr Leu Ser Tyr Tyr
20
<210> 264
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 264
Leu Arg Met Lys Ala Val Ala Glu Ile Thr Val Ala Thr Ser Arg Thr
1 5 10 15
Leu Ser Tyr Tyr
20
<210> 265
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 265
Leu Arg Met Lys Ala Val Ala Ile Thr Val Ala Thr Ser Arg Thr Leu
1 5 10 15
Ser Tyr Tyr
<210> 266
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 266
Leu Arg Met Lys Ala Val Ala Ile Thr Val Ala Thr Ser Arg Thr Leu
1 5 10 15
<210> 267
<211> 23
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 267
Leu Arg Met Lys Ala Val Ala Thr Leu Ser Tyr Tyr Lys Leu Gly Ala
1 5 10 15
Ser Gln Arg Val Ala Gly Asp
20
<210> 268
<211> 23
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 268
Leu Arg Met Lys Ala Val Ala Thr Leu Ser Tyr Tyr Lys Leu Gly Ala
1 5 10 15
Ser Gln Arg Val Ala Gly Asp
20
<210> 269
<211> 23
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 269
Leu Arg Met Lys Ala Val Ala Thr Leu Ser Tyr Tyr Lys Leu Gly Ala
1 5 10 15
Ser Gln Arg Val Ala Gly Asp
20
<210> 270
<211> 23
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 270
Leu Arg Met Lys Ala Val Ala Thr Leu Ser Tyr Tyr Lys Leu Gly Ala
1 5 10 15
Ser Gln Arg Val Ala Gly Asp
20
<210> 271
<211> 23
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 271
Leu Arg Met Lys Ala Val Ala Thr Leu Ser Tyr Tyr Lys Leu Gly Ala
1 5 10 15
Ser Gln Arg Val Ala Gly Asp
20
<210> 272
<211> 24
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 272
Leu Arg Met Lys Ala Val Ala Ile Gly Asn Tyr Lys Leu Asn Thr Asp
1 5 10 15
His Ser Ser Ser Ser Asp Asn Ile
20
<210> 273
<211> 23
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 273
Leu Arg Met Lys Ala Val Ala Gly Asn Tyr Lys Leu Asn Thr Asp His
1 5 10 15
Ser Ser Ser Ser Asp Asn Ile
20
<210> 274
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 274
Leu Arg Met Lys Ala Val Ala Asn Tyr Lys Leu Asn Thr Asp His Ser
1 5 10 15
Ser Ser Ser Asp Asn Ile
20
<210> 275
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 275
Leu Arg Met Lys Ala Val Ala Tyr Lys Leu Asn Thr Asp His Ser Ser
1 5 10 15
Ser Ser Asp Asn Ile
20
<210> 276
<211> 18
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 276
Leu Arg Met Lys Ala Val Ala Tyr Lys Leu Asn Thr Asp His Ser Ser
1 5 10 15
Ser Ser
<210> 277
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 277
Leu Arg Met Lys Ala Val Ala Pro Pro Ala Tyr Thr Asn Ser Phe Thr
1 5 10 15
Arg Gly Val Tyr Tyr Pro
20
<210> 278
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 278
Leu Arg Met Lys Ala Val Ala Pro Ala Tyr Thr Asn Ser Phe Thr Arg
1 5 10 15
Gly Val Tyr Tyr Pro
20
<210> 279
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 279
Leu Arg Met Lys Ala Val Ala Ala Tyr Thr Asn Ser Phe Thr Arg Gly
1 5 10 15
Val Tyr Tyr Pro
20
<210> 280
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 280
Leu Arg Met Lys Ala Val Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val
1 5 10 15
Tyr Tyr Pro
<210> 281
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 281
Leu Arg Met Lys Ala Val Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val
1 5 10 15
<210> 282
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 282
Leu Arg Met Lys Ala Val Ala Gln Asp Leu Phe Leu Pro Phe Phe Ser
1 5 10 15
Asn Val Thr Trp Phe His
20
<210> 283
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 283
Leu Arg Met Lys Ala Val Ala Asp Leu Phe Leu Pro Phe Phe Ser Asn
1 5 10 15
Val Thr Trp Phe His
20
<210> 284
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 284
Leu Arg Met Lys Ala Val Ala Leu Phe Leu Pro Phe Phe Ser Asn Val
1 5 10 15
Thr Trp Phe His
20
<210> 285
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 285
Leu Arg Met Lys Ala Val Ala Phe Leu Pro Phe Phe Ser Asn Val Thr
1 5 10 15
Trp Phe His
<210> 286
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 286
Leu Arg Met Lys Ala Val Ala Phe Leu Pro Phe Phe Ser Asn Val Thr
1 5 10 15
<210> 287
<211> 23
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 287
Leu Arg Met Lys Ala Val Ala Asn Val Thr Trp Phe His Ala Ile His
1 5 10 15
Val Ser Gly Thr Asn Gly Thr
20
<210> 288
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 288
Leu Arg Met Lys Ala Val Ala Val Thr Trp Phe His Ala Ile His Val
1 5 10 15
Ser Gly Thr Asn Gly Thr
20
<210> 289
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 289
Leu Arg Met Lys Ala Val Ala Thr Trp Phe His Ala Ile His Val Ser
1 5 10 15
Gly Thr Asn Gly Thr
20
<210> 290
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 290
Leu Arg Met Lys Ala Val Ala Trp Phe His Ala Ile His Val Ser Gly
1 5 10 15
Thr Asn Gly Thr
20
<210> 291
<211> 17
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 291
Leu Arg Met Lys Ala Val Ala Trp Phe His Ala Ile His Val Ser Gly
1 5 10 15
Thr
<210> 292
<211> 24
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 292
Leu Arg Met Lys Ala Val Ala Asn Asp Gly Val Tyr Phe Ala Ser Thr
1 5 10 15
Glu Lys Ser Asn Ile Ile Arg Gly
20
<210> 293
<211> 23
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 293
Leu Arg Met Lys Ala Val Ala Asp Gly Val Tyr Phe Ala Ser Thr Glu
1 5 10 15
Lys Ser Asn Ile Ile Arg Gly
20
<210> 294
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 294
Leu Arg Met Lys Ala Val Ala Gly Val Tyr Phe Ala Ser Thr Glu Lys
1 5 10 15
Ser Asn Ile Ile Arg Gly
20
<210> 295
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 295
Leu Arg Met Lys Ala Val Ala Val Tyr Phe Ala Ser Thr Glu Lys Ser
1 5 10 15
Asn Ile Ile Arg Gly
20
<210> 296
<211> 18
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 296
Leu Arg Met Lys Ala Val Ala Val Tyr Phe Ala Ser Thr Glu Lys Ser
1 5 10 15
Asn Ile
<210> 297
<211> 24
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 297
Leu Arg Met Lys Ala Val Ala Thr Gln Ser Leu Leu Ile Val Asn Asn
1 5 10 15
Ala Thr Asn Val Val Ile Lys Val
20
<210> 298
<211> 23
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 298
Leu Arg Met Lys Ala Val Ala Gln Ser Leu Leu Ile Val Asn Asn Ala
1 5 10 15
Thr Asn Val Val Ile Lys Val
20
<210> 299
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 299
Leu Arg Met Lys Ala Val Ala Ser Leu Leu Ile Val Asn Asn Ala Thr
1 5 10 15
Asn Val Val Ile Lys Val
20
<210> 300
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 300
Leu Arg Met Lys Ala Val Ala Leu Leu Ile Val Asn Asn Ala Thr Asn
1 5 10 15
Val Val Ile Lys Val
20
<210> 301
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 301
Leu Arg Met Lys Ala Val Ala Leu Leu Ile Val Asn Asn Ala Thr Asn
1 5 10 15
Val Val Ile
<210> 302
<211> 24
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 302
Leu Arg Met Lys Ala Val Ala Phe Leu Gly Val Tyr Tyr His Lys Asn
1 5 10 15
Asn Lys Ser Trp Met Glu Ser Glu
20
<210> 303
<211> 23
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 303
Leu Arg Met Lys Ala Val Ala Leu Gly Val Tyr Tyr His Lys Asn Asn
1 5 10 15
Lys Ser Trp Met Glu Ser Glu
20
<210> 304
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 304
Leu Arg Met Lys Ala Val Ala Gly Val Tyr Tyr His Lys Asn Asn Lys
1 5 10 15
Ser Trp Met Glu Ser Glu
20
<210> 305
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 305
Leu Arg Met Lys Ala Val Ala Val Tyr Tyr His Lys Asn Asn Lys Ser
1 5 10 15
Trp Met Glu Ser Glu
20
<210> 306
<211> 18
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 306
Leu Arg Met Lys Ala Val Ala Val Tyr Tyr His Lys Asn Asn Lys Ser
1 5 10 15
Trp Met
<210> 307
<211> 25
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 307
Leu Arg Met Lys Ala Val Ala Glu Ser Glu Phe Arg Val Tyr Ser Ser
1 5 10 15
Ala Asn Asn Cys Thr Phe Glu Tyr Val
20 25
<210> 308
<211> 24
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 308
Leu Arg Met Lys Ala Val Ala Ser Glu Phe Arg Val Tyr Ser Ser Ala
1 5 10 15
Asn Asn Cys Thr Phe Glu Tyr Val
20
<210> 309
<211> 23
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 309
Leu Arg Met Lys Ala Val Ala Glu Phe Arg Val Tyr Ser Ser Ala Asn
1 5 10 15
Asn Cys Thr Phe Glu Tyr Val
20
<210> 310
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 310
Leu Arg Met Lys Ala Val Ala Phe Arg Val Tyr Ser Ser Ala Asn Asn
1 5 10 15
Cys Thr Phe Glu Tyr Val
20
<210> 311
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 311
Leu Arg Met Lys Ala Val Ala Phe Arg Val Tyr Ser Ser Ala Asn Asn
1 5 10 15
Cys Thr Phe
<210> 312
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 312
Leu Arg Met Lys Ala Val Ala Asp Gly Tyr Phe Lys Ile Tyr Ser Lys
1 5 10 15
His Thr Pro Ile Asn Leu
20
<210> 313
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 313
Leu Arg Met Lys Ala Val Ala Gly Tyr Phe Lys Ile Tyr Ser Lys His
1 5 10 15
Thr Pro Ile Asn Leu
20
<210> 314
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 314
Leu Arg Met Lys Ala Val Ala Tyr Phe Lys Ile Tyr Ser Lys His Thr
1 5 10 15
Pro Ile Asn Leu
20
<210> 315
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 315
Leu Arg Met Lys Ala Val Ala Phe Lys Ile Tyr Ser Lys His Thr Pro
1 5 10 15
Ile Asn Leu
<210> 316
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 316
Leu Arg Met Lys Ala Val Ala Phe Lys Ile Tyr Ser Lys His Thr Pro
1 5 10 15
<210> 317
<211> 24
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 317
Leu Arg Met Lys Ala Val Ala Pro Arg Thr Phe Leu Leu Lys Tyr Asn
1 5 10 15
Glu Asn Gly Thr Ile Thr Asp Ala
20
<210> 318
<211> 23
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 318
Leu Arg Met Lys Ala Val Ala Arg Thr Phe Leu Leu Lys Tyr Asn Glu
1 5 10 15
Asn Gly Thr Ile Thr Asp Ala
20
<210> 319
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 319
Leu Arg Met Lys Ala Val Ala Thr Phe Leu Leu Lys Tyr Asn Glu Asn
1 5 10 15
Gly Thr Ile Thr Asp Ala
20
<210> 320
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 320
Leu Arg Met Lys Ala Val Ala Phe Leu Leu Lys Tyr Asn Glu Asn Gly
1 5 10 15
Thr Ile Thr Asp Ala
20
<210> 321
<211> 18
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 321
Leu Arg Met Lys Ala Val Ala Phe Leu Leu Lys Tyr Asn Glu Asn Gly
1 5 10 15
Thr Ile
<210> 322
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 322
Leu Arg Met Lys Ala Val Ala Thr Ser Asn Phe Arg Val Gln Pro Thr
1 5 10 15
Glu Ser Ile Val Arg Phe
20
<210> 323
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 323
Leu Arg Met Lys Ala Val Ala Ser Asn Phe Arg Val Gln Pro Thr Glu
1 5 10 15
Ser Ile Val Arg Phe
20
<210> 324
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 324
Leu Arg Met Lys Ala Val Ala Asn Phe Arg Val Gln Pro Thr Glu Ser
1 5 10 15
Ile Val Arg Phe
20
<210> 325
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 325
Leu Arg Met Lys Ala Val Ala Phe Arg Val Gln Pro Thr Glu Ser Ile
1 5 10 15
Val Arg Phe
<210> 326
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 326
Leu Arg Met Lys Ala Val Ala Phe Arg Val Gln Pro Thr Glu Ser Ile
1 5 10 15
<210> 327
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 327
Leu Arg Met Lys Ala Val Ala Phe Gly Glu Val Phe Asn Ala Thr Arg
1 5 10 15
Phe Ala Ser Val Tyr Ala
20
<210> 328
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 328
Leu Arg Met Lys Ala Val Ala Gly Glu Val Phe Asn Ala Thr Arg Phe
1 5 10 15
Ala Ser Val Tyr Ala
20
<210> 329
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 329
Leu Arg Met Lys Ala Val Ala Glu Val Phe Asn Ala Thr Arg Phe Ala
1 5 10 15
Ser Val Tyr Ala
20
<210> 330
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 330
Leu Arg Met Lys Ala Val Ala Val Phe Asn Ala Thr Arg Phe Ala Ser
1 5 10 15
Val Tyr Ala
<210> 331
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 331
Leu Arg Met Lys Ala Val Ala Val Phe Asn Ala Thr Arg Phe Ala Ser
1 5 10 15
<210> 332
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 332
Leu Arg Met Lys Ala Val Ala Phe Ala Ser Val Tyr Ala Trp Asn Arg
1 5 10 15
Lys Arg Ile Ser Asn
20
<210> 333
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 333
Leu Arg Met Lys Ala Val Ala Ala Ser Val Tyr Ala Trp Asn Arg Lys
1 5 10 15
Arg Ile Ser Asn
20
<210> 334
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 334
Leu Arg Met Lys Ala Val Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg
1 5 10 15
Ile Ser Asn
<210> 335
<211> 18
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 335
Leu Arg Met Lys Ala Val Ala Val Tyr Ala Trp Asn Arg Lys Arg Ile
1 5 10 15
Ser Asn
<210> 336
<211> 17
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 336
Leu Arg Met Lys Ala Val Ala Val Tyr Ala Trp Asn Arg Lys Arg Ile
1 5 10 15
Ser
<210> 337
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 337
Leu Arg Met Lys Ala Val Ala Val Ala Asp Tyr Ser Val Leu Tyr Asn
1 5 10 15
Ser Ala Ser Phe Ser Thr
20
<210> 338
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 338
Leu Arg Met Lys Ala Val Ala Ala Asp Tyr Ser Val Leu Tyr Asn Ser
1 5 10 15
Ala Ser Phe Ser Thr
20
<210> 339
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 339
Leu Arg Met Lys Ala Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala
1 5 10 15
Ser Phe Ser Thr
20
<210> 340
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 340
Leu Arg Met Lys Ala Val Ala Tyr Ser Val Leu Tyr Asn Ser Ala Ser
1 5 10 15
Phe Ser Thr
<210> 341
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 341
Leu Arg Met Lys Ala Val Ala Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg
1 5 10 15
Leu Phe Arg Lys Ser Asn
20
<210> 342
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 342
Leu Arg Met Lys Ala Val Ala Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu
1 5 10 15
Phe Arg Lys Ser Asn
20
<210> 343
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 343
Leu Arg Met Lys Ala Val Ala Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe
1 5 10 15
Arg Lys Ser Asn
20
<210> 344
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 344
Leu Arg Met Lys Ala Val Ala Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg
1 5 10 15
Lys Ser Asn
<210> 345
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 345
Leu Arg Met Lys Ala Val Ala Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg
1 5 10 15
<210> 346
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 346
Leu Arg Met Lys Ala Val Ala Asn Tyr Leu Tyr Arg Leu Phe Arg Lys
1 5 10 15
Ser Asn Leu Lys Pro Phe
20
<210> 347
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 347
Leu Arg Met Lys Ala Val Ala Tyr Leu Tyr Arg Leu Phe Arg Lys Ser
1 5 10 15
Asn Leu Lys Pro Phe
20
<210> 348
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 348
Leu Arg Met Lys Ala Val Ala Leu Tyr Arg Leu Phe Arg Lys Ser Asn
1 5 10 15
Leu Lys Pro Phe
20
<210> 349
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 349
Leu Arg Met Lys Ala Val Ala Tyr Arg Leu Phe Arg Lys Ser Asn Leu
1 5 10 15
Lys Pro Phe
<210> 350
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 350
Leu Arg Met Lys Ala Val Ala Tyr Arg Leu Phe Arg Lys Ser Asn Leu
1 5 10 15
<210> 351
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 351
Leu Arg Met Lys Ala Val Ala Arg Leu Phe Arg Lys Ser Asn Leu Lys
1 5 10 15
Pro Phe Glu Arg Asp
20
<210> 352
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 352
Leu Arg Met Lys Ala Val Ala Leu Phe Arg Lys Ser Asn Leu Lys Pro
1 5 10 15
Phe Glu Arg Asp
20
<210> 353
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 353
Leu Arg Met Lys Ala Val Ala Phe Arg Lys Ser Asn Leu Lys Pro Phe
1 5 10 15
Glu Arg Asp
<210> 354
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 354
Leu Arg Met Lys Ala Val Ala Phe Arg Lys Ser Asn Leu Lys Pro Phe
1 5 10 15
<210> 355
<211> 25
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 355
Leu Arg Met Lys Ala Val Ala Val Glu Gly Phe Asn Cys Tyr Phe Pro
1 5 10 15
Leu Gln Ser Tyr Gly Phe Gln Pro Thr
20 25
<210> 356
<211> 24
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 356
Leu Arg Met Lys Ala Val Ala Glu Gly Phe Asn Cys Tyr Phe Pro Leu
1 5 10 15
Gln Ser Tyr Gly Phe Gln Pro Thr
20
<210> 357
<211> 23
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 357
Leu Arg Met Lys Ala Val Ala Gly Phe Asn Cys Tyr Phe Pro Leu Gln
1 5 10 15
Ser Tyr Gly Phe Gln Pro Thr
20
<210> 358
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 358
Leu Arg Met Lys Ala Val Ala Phe Asn Cys Tyr Phe Pro Leu Gln Ser
1 5 10 15
Tyr Gly Phe Gln Pro Thr
20
<210> 359
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 359
Leu Arg Met Lys Ala Val Ala Phe Asn Cys Tyr Phe Pro Leu Gln Ser
1 5 10 15
Tyr Gly Phe
<210> 360
<211> 24
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 360
Leu Arg Met Lys Ala Val Ala Leu Gln Ser Tyr Gly Phe Gln Pro Thr
1 5 10 15
Asn Gly Val Gly Tyr Gln Pro Tyr
20
<210> 361
<211> 23
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 361
Leu Arg Met Lys Ala Val Ala Gln Ser Tyr Gly Phe Gln Pro Thr Asn
1 5 10 15
Gly Val Gly Tyr Gln Pro Tyr
20
<210> 362
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 362
Leu Arg Met Lys Ala Val Ala Ser Tyr Gly Phe Gln Pro Thr Asn Gly
1 5 10 15
Val Gly Tyr Gln Pro Tyr
20
<210> 363
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 363
Leu Arg Met Lys Ala Val Ala Tyr Gly Phe Gln Pro Thr Asn Gly Val
1 5 10 15
Gly Tyr Gln Pro Tyr
20
<210> 364
<211> 18
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 364
Leu Arg Met Lys Ala Val Ala Tyr Gly Phe Gln Pro Thr Asn Gly Val
1 5 10 15
Gly Tyr
<210> 365
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 365
Leu Arg Met Lys Ala Val Ala Val Leu Ser Phe Glu Leu Leu His Ala
1 5 10 15
Pro Ala Thr Val Cys Gly
20
<210> 366
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 366
Leu Arg Met Lys Ala Val Ala Leu Ser Phe Glu Leu Leu His Ala Pro
1 5 10 15
Ala Thr Val Cys Gly
20
<210> 367
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 367
Leu Arg Met Lys Ala Val Ala Ser Phe Glu Leu Leu His Ala Pro Ala
1 5 10 15
Thr Val Cys Gly
20
<210> 368
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 368
Leu Arg Met Lys Ala Val Ala Phe Glu Leu Leu His Ala Pro Ala Thr
1 5 10 15
Val Cys Gly
<210> 369
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 369
Leu Arg Met Lys Ala Val Ala Phe Glu Leu Leu His Ala Pro Ala Thr
1 5 10 15
<210> 370
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 370
Leu Arg Met Lys Ala Val Ala Asn Lys Cys Val Asn Phe Asn Phe Asn
1 5 10 15
Gly Leu Thr Gly Thr Gly
20
<210> 371
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 371
Leu Arg Met Lys Ala Val Ala Lys Cys Val Asn Phe Asn Phe Asn Gly
1 5 10 15
Leu Thr Gly Thr Gly
20
<210> 372
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 372
Leu Arg Met Lys Ala Val Ala Cys Val Asn Phe Asn Phe Asn Gly Leu
1 5 10 15
Thr Gly Thr Gly
20
<210> 373
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 373
Leu Arg Met Lys Ala Val Ala Val Asn Phe Asn Phe Asn Gly Leu Thr
1 5 10 15
Gly Thr Gly
<210> 374
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 374
Leu Arg Met Lys Ala Val Ala Val Asn Phe Asn Phe Asn Gly Leu Thr
1 5 10 15
<210> 375
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 375
Leu Arg Met Lys Ala Val Ala Asn Phe Asn Phe Asn Gly Leu Thr Gly
1 5 10 15
Thr Gly Val Leu Thr Glu
20
<210> 376
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 376
Leu Arg Met Lys Ala Val Ala Phe Asn Phe Asn Gly Leu Thr Gly Thr
1 5 10 15
Gly Val Leu Thr Glu
20
<210> 377
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 377
Leu Arg Met Lys Ala Val Ala Asn Phe Asn Gly Leu Thr Gly Thr Gly
1 5 10 15
Val Leu Thr Glu
20
<210> 378
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 378
Leu Arg Met Lys Ala Val Ala Phe Asn Gly Leu Thr Gly Thr Gly Val
1 5 10 15
Leu Thr Glu
<210> 379
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 379
Leu Arg Met Lys Ala Val Ala Phe Asn Gly Leu Thr Gly Thr Gly Val
1 5 10 15
<210> 380
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 380
Leu Arg Met Lys Ala Val Ala Thr Gln Leu Asn Arg Ala Leu Thr Gly
1 5 10 15
Ile Ala Val Glu Gln
20
<210> 381
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 381
Leu Arg Met Lys Ala Val Ala Gln Leu Asn Arg Ala Leu Thr Gly Ile
1 5 10 15
Ala Val Glu Gln
20
<210> 382
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 382
Leu Arg Met Lys Ala Val Ala Leu Asn Arg Ala Leu Thr Gly Ile Ala
1 5 10 15
Val Glu Gln
<210> 383
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 383
Leu Arg Met Lys Ala Val Ala Leu Asn Arg Ala Leu Thr Gly Ile Ala
1 5 10 15
<210> 384
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 384
Leu Arg Met Lys Ala Val Ala Thr Asp Glu Met Ile Ala Gln Tyr Thr
1 5 10 15
Ser Ala Leu Leu Ala Gly
20
<210> 385
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 385
Leu Arg Met Lys Ala Val Ala Asp Glu Met Ile Ala Gln Tyr Thr Ser
1 5 10 15
Ala Leu Leu Ala Gly
20
<210> 386
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 386
Leu Arg Met Lys Ala Val Ala Glu Met Ile Ala Gln Tyr Thr Ser Ala
1 5 10 15
Leu Leu Ala Gly
20
<210> 387
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 387
Leu Arg Met Lys Ala Val Ala Met Ile Ala Gln Tyr Thr Ser Ala Leu
1 5 10 15
Leu Ala Gly
<210> 388
<211> 17
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 388
Leu Arg Met Lys Ala Val Ala Met Ile Ala Gln Tyr Thr Ser Ala Leu
1 5 10 15
Leu
<210> 389
<211> 24
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 389
Leu Arg Met Lys Ala Val Ala Gln Ile Pro Phe Ala Met Gln Met Ala
1 5 10 15
Tyr Arg Phe Asn Gly Ile Gly Val
20
<210> 390
<211> 23
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 390
Leu Arg Met Lys Ala Val Ala Ile Pro Phe Ala Met Gln Met Ala Tyr
1 5 10 15
Arg Phe Asn Gly Ile Gly Val
20
<210> 391
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 391
Leu Arg Met Lys Ala Val Ala Pro Phe Ala Met Gln Met Ala Tyr Arg
1 5 10 15
Phe Asn Gly Ile Gly Val
20
<210> 392
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 392
Leu Arg Met Lys Ala Val Ala Phe Ala Met Gln Met Ala Tyr Arg Phe
1 5 10 15
Asn Gly Ile Gly Val
20
<210> 393
<211> 18
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 393
Leu Arg Met Lys Ala Val Ala Phe Ala Met Gln Met Ala Tyr Arg Phe
1 5 10 15
Asn Gly
<210> 394
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 394
Leu Arg Met Lys Ala Val Ala Gln Lys Leu Ile Ala Asn Gln Phe Asn
1 5 10 15
Ser Ala Ile Gly Lys Ile
20
<210> 395
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 395
Leu Arg Met Lys Ala Val Ala Lys Leu Ile Ala Asn Gln Phe Asn Ser
1 5 10 15
Ala Ile Gly Lys Ile
20
<210> 396
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 396
Leu Arg Met Lys Ala Val Ala Leu Ile Ala Asn Gln Phe Asn Ser Ala
1 5 10 15
Ile Gly Lys Ile
20
<210> 397
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 397
Leu Arg Met Lys Ala Val Ala Ile Ala Asn Gln Phe Asn Ser Ala Ile
1 5 10 15
Gly Lys Ile
<210> 398
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 398
Leu Arg Met Lys Ala Val Ala Ile Ala Asn Gln Phe Asn Ser Ala Ile
1 5 10 15
<210> 399
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 399
Leu Arg Met Lys Ala Val Ala Ala Asn Gln Phe Asn Ser Ala Ile Gly
1 5 10 15
Lys Ile Gln Asp Ser Leu
20
<210> 400
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 400
Leu Arg Met Lys Ala Val Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys
1 5 10 15
Ile Gln Asp Ser Leu
20
<210> 401
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 401
Leu Arg Met Lys Ala Val Ala Gln Phe Asn Ser Ala Ile Gly Lys Ile
1 5 10 15
Gln Asp Ser Leu
20
<210> 402
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 402
Leu Arg Met Lys Ala Val Ala Phe Asn Ser Ala Ile Gly Lys Ile Gln
1 5 10 15
Asp Ser Leu
<210> 403
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 403
Leu Arg Met Lys Ala Val Ala Phe Asn Ser Ala Ile Gly Lys Ile Gln
1 5 10 15
<210> 404
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 404
Leu Arg Met Lys Ala Val Ala Thr Gly Arg Leu Gln Ser Leu Gln Thr
1 5 10 15
Tyr Val Thr Gln Gln Leu
20
<210> 405
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 405
Leu Arg Met Lys Ala Val Ala Gly Arg Leu Gln Ser Leu Gln Thr Tyr
1 5 10 15
Val Thr Gln Gln Leu
20
<210> 406
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 406
Leu Arg Met Lys Ala Val Ala Arg Leu Gln Ser Leu Gln Thr Tyr Val
1 5 10 15
Thr Gln Gln Leu
20
<210> 407
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 407
Leu Arg Met Lys Ala Val Ala Leu Gln Ser Leu Gln Thr Tyr Val Thr
1 5 10 15
Gln Gln Leu
<210> 408
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 408
Leu Arg Met Lys Ala Val Ala Leu Gln Ser Leu Gln Thr Tyr Val Thr
1 5 10 15
<210> 409
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 409
Leu Arg Met Lys Ala Val Ala Gly Lys Gly Tyr His Leu Met Ser Phe
1 5 10 15
Pro Gln Ser Ala Pro His
20
<210> 410
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 410
Leu Arg Met Lys Ala Val Ala Lys Gly Tyr His Leu Met Ser Phe Pro
1 5 10 15
Gln Ser Ala Pro His
20
<210> 411
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 411
Leu Arg Met Lys Ala Val Ala Gly Tyr His Leu Met Ser Phe Pro Gln
1 5 10 15
Ser Ala Pro His
20
<210> 412
<211> 19
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 412
Leu Arg Met Lys Ala Val Ala Tyr His Leu Met Ser Phe Pro Gln Ser
1 5 10 15
Ala Pro His
<210> 413
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 413
Leu Arg Met Lys Ala Val Ala Tyr His Leu Met Ser Phe Pro Gln Ser
1 5 10 15
<210> 414
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 414
Leu Arg Met Lys Ala Val Ala Asp Val Val Ile Gly Ile Val Asn Asn
1 5 10 15
Thr Val Tyr Asp Pro Leu
20
<210> 415
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 415
Leu Arg Met Lys Ala Val Ala Val Val Ile Gly Ile Val Asn Asn Thr
1 5 10 15
Val Tyr Asp Pro Leu
20
<210> 416
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 416
Leu Arg Met Lys Ala Val Ala Val Ile Gly Ile Val Asn Asn Thr Val
1 5 10 15
Tyr Asp Pro Leu
20
<210> 417
<211> 17
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 417
Leu Arg Met Lys Ala Val Ala Val Ile Gly Ile Val Asn Asn Thr Val
1 5 10 15
Tyr
<210> 418
<211> 23
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 418
Leu Arg Met Lys Ala Val Ala Leu Asp Lys Tyr Phe Lys Asn His Thr
1 5 10 15
Ser Pro Asp Val Asp Leu Gly
20
<210> 419
<211> 22
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 419
Leu Arg Met Lys Ala Val Ala Asp Lys Tyr Phe Lys Asn His Thr Ser
1 5 10 15
Pro Asp Val Asp Leu Gly
20
<210> 420
<211> 21
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 420
Leu Arg Met Lys Ala Val Ala Lys Tyr Phe Lys Asn His Thr Ser Pro
1 5 10 15
Asp Val Asp Leu Gly
20
<210> 421
<211> 20
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 421
Leu Arg Met Lys Ala Val Ala Tyr Phe Lys Asn His Thr Ser Pro Asp
1 5 10 15
Val Asp Leu Gly
20
<210> 422
<211> 17
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 422
Leu Arg Met Lys Ala Val Ala Tyr Phe Lys Asn His Thr Ser Pro Asp
1 5 10 15
Val
<210> 423
<211> 1255
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 423
Met Glu Leu Ala Ala Leu Cys Arg Trp Gly Leu Leu Leu Ala Leu Leu
1 5 10 15
Pro Pro Gly Ala Ala Ser Thr Gln Val Cys Thr Gly Thr Asp Met Lys
20 25 30
Leu Arg Leu Pro Ala Ser Pro Glu Thr His Leu Asp Met Leu Arg His
35 40 45
Leu Tyr Gln Gly Cys Gln Val Val Gln Gly Asn Leu Glu Leu Thr Tyr
50 55 60
Leu Pro Thr Asn Ala Ser Leu Ser Phe Leu Gln Asp Ile Gln Glu Val
65 70 75 80
Gln Gly Tyr Val Leu Ile Ala His Asn Gln Val Arg Gln Val Pro Leu
85 90 95
Gln Arg Leu Arg Ile Val Arg Gly Thr Gln Leu Phe Glu Asp Asn Tyr
100 105 110
Ala Leu Ala Val Leu Asp Asn Gly Asp Pro Leu Asn Asn Thr Thr Pro
115 120 125
Val Thr Gly Ala Ser Pro Gly Gly Leu Arg Glu Leu Gln Leu Arg Ser
130 135 140
Leu Thr Glu Ile Leu Lys Gly Gly Val Leu Ile Gln Arg Asn Pro Gln
145 150 155 160
Leu Cys Tyr Gln Asp Thr Ile Leu Trp Lys Asp Ile Phe His Lys Asn
165 170 175
Asn Gln Leu Ala Leu Thr Leu Ile Asp Thr Asn Arg Ser Arg Ala Cys
180 185 190
His Pro Cys Ser Pro Met Cys Lys Gly Ser Arg Cys Trp Gly Glu Ser
195 200 205
Ser Glu Asp Cys Gln Ser Leu Thr Arg Thr Val Cys Ala Gly Gly Cys
210 215 220
Ala Arg Cys Lys Gly Pro Leu Pro Thr Asp Cys Cys His Glu Gln Cys
225 230 235 240
Ala Ala Gly Cys Thr Gly Pro Lys His Ser Asp Cys Leu Ala Cys Leu
245 250 255
His Phe Asn His Ser Gly Ile Cys Glu Leu His Cys Pro Ala Leu Val
260 265 270
Thr Tyr Asn Thr Asp Thr Phe Glu Ser Met Pro Asn Pro Glu Gly Arg
275 280 285
Tyr Thr Phe Gly Ala Ser Cys Val Thr Ala Cys Pro Tyr Asn Tyr Leu
290 295 300
Ser Thr Asp Val Gly Ser Cys Thr Leu Val Cys Pro Leu His Asn Gln
305 310 315 320
Glu Val Thr Ala Glu Asp Gly Thr Gln Arg Cys Glu Lys Cys Ser Lys
325 330 335
Pro Cys Ala Arg Val Cys Tyr Gly Leu Gly Met Glu His Leu Arg Glu
340 345 350
Val Arg Ala Val Thr Ser Ala Asn Ile Gln Glu Phe Ala Gly Cys Lys
355 360 365
Lys Ile Phe Gly Ser Leu Ala Phe Leu Pro Glu Ser Phe Asp Gly Asp
370 375 380
Pro Ala Ser Asn Thr Ala Pro Leu Gln Pro Glu Gln Leu Gln Val Phe
385 390 395 400
Glu Thr Leu Glu Glu Ile Thr Gly Tyr Leu Tyr Ile Ser Ala Trp Pro
405 410 415
Asp Ser Leu Pro Asp Leu Ser Val Phe Gln Asn Leu Gln Val Ile Arg
420 425 430
Gly Arg Ile Leu His Asn Gly Ala Tyr Ser Leu Thr Leu Gln Gly Leu
435 440 445
Gly Ile Ser Trp Leu Gly Leu Arg Ser Leu Arg Glu Leu Gly Ser Gly
450 455 460
Leu Ala Leu Ile His His Asn Thr His Leu Cys Phe Val His Thr Val
465 470 475 480
Pro Trp Asp Gln Leu Phe Arg Asn Pro His Gln Ala Leu Leu His Thr
485 490 495
Ala Asn Arg Pro Glu Asp Glu Cys Val Gly Glu Gly Leu Ala Cys His
500 505 510
Gln Leu Cys Ala Arg Gly His Cys Trp Gly Pro Gly Pro Thr Gln Cys
515 520 525
Val Asn Cys Ser Gln Phe Leu Arg Gly Gln Glu Cys Val Glu Glu Cys
530 535 540
Arg Val Leu Gln Gly Leu Pro Arg Glu Tyr Val Asn Ala Arg His Cys
545 550 555 560
Leu Pro Cys His Pro Glu Cys Gln Pro Gln Asn Gly Ser Val Thr Cys
565 570 575
Phe Gly Pro Glu Ala Asp Gln Cys Val Ala Cys Ala His Tyr Lys Asp
580 585 590
Pro Pro Phe Cys Val Ala Arg Cys Pro Ser Gly Val Lys Pro Asp Leu
595 600 605
Ser Tyr Met Pro Ile Trp Lys Phe Pro Asp Glu Glu Gly Ala Cys Gln
610 615 620
Pro Cys Pro Ile Asn Cys Thr His Ser Cys Val Asp Leu Asp Asp Lys
625 630 635 640
Gly Cys Pro Ala Glu Gln Arg Ala Ser Pro Leu Thr Ser Ile Ile Ser
645 650 655
Ala Val Val Gly Ile Leu Leu Val Val Val Leu Gly Val Val Phe Gly
660 665 670
Ile Leu Ile Lys Arg Arg Gln Gln Lys Ile Arg Lys Tyr Thr Met Arg
675 680 685
Arg Leu Leu Gln Glu Thr Glu Leu Val Glu Pro Leu Thr Pro Ser Gly
690 695 700
Ala Met Pro Asn Gln Ala Gln Met Arg Ile Leu Lys Glu Thr Glu Leu
705 710 715 720
Arg Lys Val Lys Val Leu Gly Ser Gly Ala Phe Gly Thr Val Tyr Lys
725 730 735
Gly Ile Trp Ile Pro Asp Gly Glu Asn Val Lys Ile Pro Val Ala Ile
740 745 750
Lys Val Leu Arg Glu Asn Thr Ser Pro Lys Ala Asn Lys Glu Ile Leu
755 760 765
Asp Glu Ala Tyr Val Met Ala Gly Val Gly Ser Pro Tyr Val Ser Arg
770 775 780
Leu Leu Gly Ile Cys Leu Thr Ser Thr Val Gln Leu Val Thr Gln Leu
785 790 795 800
Met Pro Tyr Gly Cys Leu Leu Asp His Val Arg Glu Asn Arg Gly Arg
805 810 815
Leu Gly Ser Gln Asp Leu Leu Asn Trp Cys Met Gln Ile Ala Lys Gly
820 825 830
Met Ser Tyr Leu Glu Asp Val Arg Leu Val His Arg Asp Leu Ala Ala
835 840 845
Arg Asn Val Leu Val Lys Ser Pro Asn His Val Lys Ile Thr Asp Phe
850 855 860
Gly Leu Ala Arg Leu Leu Asp Ile Asp Glu Thr Glu Tyr His Ala Asp
865 870 875 880
Gly Gly Lys Val Pro Ile Lys Trp Met Ala Leu Glu Ser Ile Leu Arg
885 890 895
Arg Arg Phe Thr His Gln Ser Asp Val Trp Ser Tyr Gly Val Thr Val
900 905 910
Trp Glu Leu Met Thr Phe Gly Ala Lys Pro Tyr Asp Gly Ile Pro Ala
915 920 925
Arg Glu Ile Pro Asp Leu Leu Glu Lys Gly Glu Arg Leu Pro Gln Pro
930 935 940
Pro Ile Cys Thr Ile Asp Val Tyr Met Ile Met Val Lys Cys Trp Met
945 950 955 960
Ile Asp Ser Glu Cys Arg Pro Arg Phe Arg Glu Leu Val Ser Glu Phe
965 970 975
Ser Arg Met Ala Arg Asp Pro Gln Arg Phe Val Val Ile Gln Asn Glu
980 985 990
Asp Leu Gly Pro Ala Ser Pro Leu Asp Ser Thr Phe Tyr Arg Ser Leu
995 1000 1005
Leu Glu Asp Asp Asp Met Gly Asp Leu Val Asp Ala Glu Glu Tyr Leu
1010 1015 1020
Val Pro Gln Gln Gly Phe Phe Cys Pro Asp Pro Ala Pro Gly Ala Gly
1025 1030 1035 1040
Gly Met Val His His Arg His Arg Ser Ser Ser Thr Arg Ser Gly Gly
1045 1050 1055
Gly Asp Leu Thr Leu Gly Leu Glu Pro Ser Glu Glu Glu Ala Pro Arg
1060 1065 1070
Ser Pro Leu Ala Pro Ser Glu Gly Ala Gly Ser Asp Val Phe Asp Gly
1075 1080 1085
Asp Leu Gly Met Gly Ala Ala Lys Gly Leu Gln Ser Leu Pro Thr His
1090 1095 1100
Asp Pro Ser Pro Leu Gln Arg Tyr Ser Glu Asp Pro Thr Val Pro Leu
1105 1110 1115 1120
Pro Ser Glu Thr Asp Gly Tyr Val Ala Pro Leu Thr Cys Ser Pro Gln
1125 1130 1135
Pro Glu Tyr Val Asn Gln Pro Asp Val Arg Pro Gln Pro Pro Ser Pro
1140 1145 1150
Arg Glu Gly Pro Leu Pro Ala Ala Arg Pro Ala Gly Ala Thr Leu Glu
1155 1160 1165
Arg Pro Lys Thr Leu Ser Pro Gly Lys Asn Gly Val Val Lys Asp Val
1170 1175 1180
Phe Ala Phe Gly Gly Ala Val Glu Asn Pro Glu Tyr Leu Thr Pro Gln
1185 1190 1195 1200
Gly Gly Ala Ala Pro Gln Pro His Pro Pro Pro Ala Phe Ser Pro Ala
1205 1210 1215
Phe Asp Asn Leu Tyr Tyr Trp Asp Gln Asp Pro Pro Glu Arg Gly Ala
1220 1225 1230
Pro Pro Ser Thr Phe Lys Gly Thr Pro Thr Ala Glu Asn Pro Glu Tyr
1235 1240 1245
Leu Gly Leu Asp Val Pro Val
1250 1255
<210> 424
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 424
Phe Val Val Ile Gln Asn Glu Asp Leu
1 5
<210> 425
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 425
Leu Arg Ile Val Arg Gly Thr Gln Leu
1 5
<210> 426
<211> 8
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 426
Met Met Val Lys Cys Trp Met Ile
1 5
<210> 427
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 427
Leu Arg Arg Arg Phe Thr His Gln Ser
1 5
<210> 428
<211> 8
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 428
Tyr Thr Met Arg Arg Leu Leu Glu
1 5
<210> 429
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 429
Val Val Leu Gly Val Val Phe Gly Ile
1 5
<210> 430
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 430
Met Val His His Arg His Arg Ser Ser
1 5
<210> 431
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 431
Leu Ser Val Phe Gln Asn Leu Gln Val
1 5
<210> 432
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 432
Leu Thr Leu Ile Asp Thr Asn Arg Ser
1 5
<210> 433
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 433
Phe Gly Ile Leu Ile Lys Arg Arg Gln
1 5
<210> 434
<211> 8
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 434
Leu Val Phe Glu Thr Leu Glu Glu
1 5
<210> 435
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 435
Leu Thr Tyr Leu Pro Thr Asn Ala Ser
1 5
<210> 436
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 436
Tyr Met Ile Met Val Lys Cys Trp Met
1 5
<210> 437
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 437
Leu Arg Lys Val Lys Val Leu Gly Ser
1 5
<210> 438
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 438
Phe Gln Asn Leu Gln Val Ile Arg Gly
1 5
<210> 439
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 439
Val Pro Ile Lys Trp Met Ala Leu Glu Ser Ile Leu Arg Arg Arg
1 5 10 15
<210> 440
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 440
Gly Ser Pro Tyr Val Ser Arg Leu Leu Gly Ile Cys
1 5 10
<210> 441
<211> 11
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 441
Gln Leu Gln Val Phe Glu Thr Leu Glu Glu Ile
1 5 10
<210> 442
<211> 13
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 442
Leu Cys Phe Val His Thr Val Pro Trp Asp Gln Leu Phe
1 5 10
<210> 443
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 443
Gly Ile Ser Trp Leu Gly Leu Arg Ser Leu Arg Glu
1 5 10
<210> 444
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 444
Glu Phe Ser Arg Met Ala Arg Asp Pro Gln Arg Phe
1 5 10
<210> 445
<211> 12
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 445
Phe Asp Gly Asp Leu Gly Met Ala Ala Lys Gly Leu
1 5 10
<210> 446
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 446
His Ile Leu Asp Met Leu Arg His Leu Tyr Gln Gly Cys Gln Val Val
1 5 10 15
<210> 447
<211> 16
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 447
Leu Arg Ile Val Arg Gly Thr Gln Leu Phe Glu Asp Asn Tyr Ala Leu
1 5 10 15
<210> 448
<211> 18
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 448
Thr Gln Arg Cys Glu Lys Cys Ser Lys Pro Cys Ala Arg Val Cys Tyr
1 5 10 15
Gly Leu
<210> 449
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 449
Leu Gly Ser Gly Ala Phe Gly Thr Val Tyr Lys Gly Ile Trp Ile
1 5 10 15
<210> 450
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 450
Pro Ala Arg Glu Ile Pro Asp Leu Leu Glu Lys Gly Glu Arg Leu
1 5 10 15
<210> 451
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 451
Thr Leu Glu Arg Pro Lys Thr Leu Ser Pro Gly Lys Asn Gly Val
1 5 10 15
<210> 452
<211> 18
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 452
Lys Lys Ile Phe Gly Ser Leu Leu Ala Phe Leu Pro Glu Ser Phe Asp
1 5 10 15
Gly Asp
<210> 453
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 453
Arg Gln Gln Lys Ile Arg Lys Tyr Thr Met Arg Arg Leu Leu Glu
1 5 10 15
<210> 454
<211> 14
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 454
Glu Leu Val Ser Glu Phe Ser Arg Met Ala Arg Asp Pro Gln
1 5 10
<210> 455
<211> 10
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 455
Leu Arg Ile Val Arg Thr Gly Thr Gln Leu
1 5 10
<210> 456
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 456
Leu Val Ser Glu Phe Ser Arg Met Ala
1 5
<210> 457
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 457
Ile Leu Leu Val Val Val Leu Gly Val
1 5
<210> 458
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 458
Lys Ile Phe Gly Ser Leu Ala Phe Leu
1 5
<210> 459
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 459
Ile Leu Trp Lys Asp Ile Phe His Lys
1 5
<210> 460
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 460
Thr Tyr Leu Pro Thr Asn Ala Ser Leu
1 5
<210> 461
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 461
Gln Leu Phe Glu Asp Asn Tyr Ala Leu
1 5
<210> 462
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 462
Glu Tyr Val Asn Ala Arg His Cys Leu
1 5
<210> 463
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 463
Ala Tyr Ser Leu Thr Leu Gln Gly Leu
1 5
<210> 464
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 464
Ser Tyr Gly Trp Thr Val Trp Glu Leu
1 5
<210> 465
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 465
Glu Tyr Leu Val Pro Gln Gln Gly Phe
1 5
<210> 466
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 466
Arg Leu Ile Gln Glu Thr Glu Leu Val
1 5
<210> 467
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 467
Ile Leu Lys Glu Thr Glu Leu Arg Lys
1 5
<210> 468
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 468
Val Leu Arg Glu Asn Thr Ser Pro Lys
1 5
<210> 469
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 469
Ile Leu Ile Lys Arg Arg Gln Gln Lys
1 5
<210> 470
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 470
Gln Leu Phe Glu Asp Asn Tyr Ala Leu
1 5
<210> 471
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 471
Lys Ile Phe Gly Ser Leu Ala Phe Leu
1 5
<210> 472
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 472
Arg Leu Leu Gln Glu Thr Glu Leu Val
1 5
<210> 473
<211> 10
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 473
Ile Leu His Ile Asn Gly Ala Tyr Ser Leu
1 5 10
<210> 474
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 474
Val Val Leu Gly Val Val Phe Gly Ile
1 5
<210> 475
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 475
Tyr Met Ile Met Val Lys Cys Trp Met
1 5
<210> 476
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 476
Ile Ile Ser Ala Val Val Gly Ile Leu
1 5
<210> 477
<211> 10
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 477
Phe Leu Ser Ala Val Val Gly Ile Leu Val
1 5 10
<210> 478
<211> 10
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 478
Val Met Ala Gly Val Gly Ser Pro Tyr Val
1 5 10
<210> 479
<211> 9
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 479
Val Leu Arg Glu Asn Thr Ser Pro Lys
1 5
<210> 480
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 480
Thr Arg Thr Val Cys Ala Gly Gly Cys Ala Arg Cys Lys Gly Pro
1 5 10 15
<210> 481
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 481
Cys Ala Gly Gly Cys Ala Arg Cys Lys Gly Pro Leu Pro Thr Asp
1 5 10 15
<210> 482
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 482
Gln Phe Leu Arg Gln Glu Cys Val Glu Glu Cys Arg Val Leu Gln
1 5 10 15
<210> 483
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 483
Val Leu Gln Gly Leu Pro Arg Glu Tyr Val Asn Ala Arg His Cys
1 5 10 15
<210> 484
<211> 15
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 484
Asn Gly Ser Val Thr Cys Phe Gly Pro Glu Ala Asp Gln Cys Val
1 5 10 15

Claims (10)

1. A T cell epitope peptide complex comprising a single peptide and/or polypeptide consisting of one or more of the amino acid sequences of SEQ ID nos. 4-209, and/or fragments and variants thereof.
2. The T-cell epitope peptide complex of claim 1, wherein 1 to 12 additional amino acids are added to the N-terminus and/or C-terminus of the amino acid sequence of SEQ ID No.4 to 209 in any ratio.
3. The T-cell epitope peptide complex of claim 2, wherein said T-cell epitope peptide complex comprises a tandem polypeptide comprising a single peptide and/or polypeptide consisting of one or more of the amino acid sequences of SEQ ID nos. 4-209, and/or fragments and variants thereof.
4. The T-cell epitope peptide complex of claim 2, wherein said T-cell epitope peptide complex comprises a chimeric or fusion polypeptide comprising a single peptide and/or polypeptide consisting of one or more of the amino acid sequences of SEQ ID No.4-209, and/or fragments and variants thereof, and/or a tandem polypeptide of claim 3.
5. A biological vector which is a nucleic acid molecule encoding a single peptide and/or polypeptide consisting of one or more of the amino acid sequences of SEQ ID No.4 to 209 and/or fragments and variants thereof, and/or a tandem polypeptide according to claim 3, and/or a chimeric or fusion polypeptide according to claim 4; the biological vector is an expression vector or a gene therapy vector, and the expression vector or the gene therapy vector comprises the nucleic acid molecule; the biological vector is a cell, and the cell comprises the expression vector.
6. An Ii-key hybridization construct, said Ii-key hybridization construct comprising:
(1) an N-terminal element comprising/consisting essentially of the residue LRMK of sequence SEQ ID No.1 and 0-12 additional sequence residues of sequence SEQ ID No. 1;
(2) an antigenic peptide binding site with MHC class II and/or class I molecules as a C-terminal element;
(3) an optional intermediate chemical structure;
the intermediate chemical structure covalently links hybridized N-terminal and C-terminal elements.
7. The Ii-key hybridization construct according to claim 6 wherein said C-terminal element is selected from the group consisting of SEQ ID No.4-209 and/or fragments and variants thereof; the C-terminal or N-terminal of SEQ ID NO.4-209 and/or fragments and variants thereof optionally comprises 0-12 additional amino acids; the C-terminal element is selected from a tandem polypeptide consisting of SEQ ID NO.4-209 and/or fragments and variants thereof; the C-terminal element is selected from chimeric or fusion polypeptides consisting of SEQ ID NO.4-209 and/or fragments and variants thereof.
8. Use of a T cell epitope peptide complex according to any one of claims 1 to 4 and/or a biological vector according to claim 5 and/or an Ii-key hybrid construct according to any one of claims 6 to 7 in the preparation of a novel coronavirus vaccine.
9. A medicament comprising a T-cell epitope peptide complex according to any one of claims 1 to 4 and/or a biological vector according to claim 5 and/or an Ii-key hybridization construct according to any one of claims 6 to 7.
10. A vaccine for the prevention and/or treatment of a neocoronaviral infection, comprising a T cell epitope peptide complex according to any one of claims 1 to 4 and/or a biological vector according to claim 5 and/or an Ii-key hybrid construct according to any one of claims 6 to 7.
CN202110504310.7A 2021-05-10 2021-05-10 T cell epitope peptide compound Pending CN114621329A (en)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060002947A1 (en) * 1999-09-14 2006-01-05 Robert Humphreys Ii-key/antigenic epitope hybrid peptide vaccines
CN112028978A (en) * 2020-09-07 2020-12-04 重庆医科大学 Novel coronavirus specific CD8+T cell epitope peptide and application thereof
CN112194711A (en) * 2020-10-15 2021-01-08 深圳市疾病预防控制中心（深圳市卫生检验中心、深圳市预防医学研究所） B cell linear epitope of novel coronavirus S protein, antibody, identification method and application
WO2021163398A1 (en) * 2020-02-14 2021-08-19 Epivax, Inc. T cell epitope clusters and related compositions useful in the prevention, diagnosis, and treatment of covid-19
CN113801208A (en) * 2021-09-29 2021-12-17 中国疾病预防控制中心病毒病预防控制所 T cell immunodetection method for novel coronavirus

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060002947A1 (en) * 1999-09-14 2006-01-05 Robert Humphreys Ii-key/antigenic epitope hybrid peptide vaccines
WO2021163398A1 (en) * 2020-02-14 2021-08-19 Epivax, Inc. T cell epitope clusters and related compositions useful in the prevention, diagnosis, and treatment of covid-19
CN112028978A (en) * 2020-09-07 2020-12-04 重庆医科大学 Novel coronavirus specific CD8+T cell epitope peptide and application thereof
CN112194711A (en) * 2020-10-15 2021-01-08 深圳市疾病预防控制中心（深圳市卫生检验中心、深圳市预防医学研究所） B cell linear epitope of novel coronavirus S protein, antibody, identification method and application
CN113801208A (en) * 2021-09-29 2021-12-17 中国疾病预防控制中心病毒病预防控制所 T cell immunodetection method for novel coronavirus

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Application publication date: 20220614