Polypeptide derived from a popamine receptor, and compositions and methods thereof

Information

  • Patent Grant
  • 5508384
  • Patent Number
    5,508,384
  • Date Filed
    Thursday, September 9, 1993
    31 years ago
  • Date Issued
    Tuesday, April 16, 1996
    28 years ago
Abstract
Compounds, compositions and methods involving purified, isolated and/or synthetic G-protein coupled receptor (GPR) polypeptides that comprise fragments, derivatives and/or consensus peptides of transmembrane domains of G-coupled receptor proteins, wherein the GPR polypeptide has biological activity selected from binding of a GPR ligand to a GPR or modulating the binding of a GPR ligand to a GPR.
Description

FIELD OF THE INVENTION
The present invention relates to compounds, compositions and methods involving synthetic, isolated and/or recombinant G-protein coupled receptor polypeptides that comprise fragments and/or consensus peptides of G-protein coupled receptors.
BACKGROUND OF THE INVENTION
The membrane protein gene superfamily of G-protein coupled receptors (GPRs) has been characterized as having seven putative transmembrane domains. The domains are believed to represent transmembrane .alpha.-helices connected by extracellular or cytoplasmic loops. Of the 74 sequenced members of this G-protein receptor superfamily, the shortest sequence of 324 amino acids represents the rat mas oncogene and the longest, of 744 amino acids, represents the human thyroid-stimulating hormone (TSH) receptor. GPRs thus include a wide range of biologically active receptors, such as hormone-, viral-, growth factor- and neuroreceptors.
G-protein coupled receptors have been characterized as including these seven conserved hydrophobic stretches of about 20-30 amino acids, connecting at least 8 divergent hydrophilic loops. The G-protein family of coupled receptors includes dopamine receptors which bind in a noncovalent but high affinity manner to neuroleptic drugs used for treating psychotic and neurological disorders. For example, the dopamine D.sub.2 receptor includes these transmembrane domains, two of which (TM III and TM V; see below) have been implicated by site-selective mutagenesis to demonstrate functional, association with D.sub.2 ligands.
Transmembrane domains of G-protein coupled receptors are designated TM1, TM2, TM3, TM4, TMS, TM6 and TM7. TM4, TM5, TM6 and TM7 are the most highly conserved and are postulated to provide sequences which impart biological activity to GPRs. Most GPRs have single conserved cysteine residues in each of the first two extracellular loops which form disulfide bonds that are believed to stabilize functional protein structure. TM3 is also implicated in signal transduction.
Phosphorylation and lipidation (palmitylation or farnesylation) of cysteine residues can influence signal transduction of some GPRs. Most GPRs contain potential phosphorylation sites (e.g., serine or theronine residues) within the third cytoplasmic loop and/or the carboxy terminus. For several GPRs, such as the .beta.-adrenoreceptor, phosphorylation by protein kinase A and/or specific receptor kinases mediates receptor desensitization.
Non-limiting examples of GPRs include cAMP receptors, adenosine receptors, .beta.-adrenergic receptors, muscarinic acetylcholine receptors, .alpha.-adrenergic receptors, serotonin receptors (5-HT), histamine H2 receptors, thrombin receptors, kinin receptors, follicle stimulating hormone receptors, opsins and rhodopsins, odorant receptors, cytomegalovirus receptor, etc. See e.g., Probst et al DNA and Cell Biology 11:1-20(1992), which is entirely incorporated herein by reference.
The ligand binding sites of GPRs are believed to comprise a hydrophilic socket formed by several GPR transmembrane domains, which socket is surrounded by hydrophobic residues of the GPRs. The hydrophilic side of each GPR transmembrane helix is postulated to face inward and form the polar ligand binding site. TM3 has been implicated in several GPRs as having a ligand binding site, such as including the TM3 aspartate residue. Additionally, TM5 serines, a TM6 asparagine and TM6 or TM7 phenylalanines or tyrosines are also implicated in ligand binding.
GPRs can be intracellularly coupled by heterotrimeric G-proteins to various intracellular enzymes, ion channels and transporters. See, e.g., Johnson et al Endoc. Rev. 10:317-331(1989) ; and Birnbaumer et al Blochem. Biophys. Acta 1031:163-224(1990) which references are incorporated entirely herein by reference. GPR agonist binding catalyzes the exchange of GTP for GDP on the .alpha.-subunit of the G-protein. Different G-protein .alpha.-subunits preferentially stimulate particular effectors to modulate various biological functions in a cell. Phosphorylation of cytoplasmic residues of GPRs has been identified as an important mechanism for the regulation of G-protein coupling of some GPRs.
As a non-limiting example of a GPR ligand, dopamine (3,4-dihydroxyphenethylamine) is a critical neurotransmitter in the central nervous system (e.g., in the substantial nigra, midbrain, and hypothalamus). Since the elucidation of the ascending mesolimbic and nigrostriatal pathways, these pathways have been found to be critical in the control of both motor initiation (nigrostriatal) behavior and affectire (mesolimbic) behavior. The clinical efficacy of the major neuroleptic antipsychotic medications has been found to correlate with the respective affinities of these agents for the dopamine D.sub.2 receptor in the brain. A dopaminergic role in the symptomatology of the major psychoses has thus been hypothesized, although it is unclear if dopamine alone is etiological, (see, e.g., Davis et al. Am. J. Psych. 148:1474-1476 (1991)). Nonetheless, this hypothesis has served as a stimulus for current research in this area.
One model for studying possible interactions of G-protein coupled receptors with their ligands has emerged from site-directed mutagenesis and biochemical analysis of the .beta.-adrenergic receptor, as well as from biophysical analysis of the interaction of retinal with opsin.
According to such a model, the binding of a GPR ligand to a G-protein coupled receptor involves multiple interactions between functional groups on the GPR ligand and residues within the hydrophophilic binding site of the receptor.
While a number of the amino acid residues in the dopamine D.sub.2 receptor have been postulated to participate in D.sub.2 ligand binding, based on results obtained from site-directed mutagenesis studies and photoaffinity labeling studies performed on the .beta.-adrenergic receptor, such studies have failed to specifically determine which residues are actually involved in binding in the D.sub.2 system. Sibley et al. Soc. Neurosci. Abs. 17:36.10, 324.5, 324.6 (1991).
The clinical use of neuroleptics has provided a means for treating patients suffering from psychotic disorders. Short-term use of neuroleptics is indicated in several types of psychotic disorders, e.g., acute psychotic episodes, regardless of type; exacerbations of schizophrenia; acute manic excitement while deferring use of lithium or awaiting onset of its effects; adjunctive therapy for major depression with prominent psychotic symptoms, or when an antidepressant or ECT alone is not successful; for agitation in delirium, dementia, or severe mental retardation while seeking to identify and treat the primary basis of the problem; in certain chronic, degenerative, or idiopathic neuropsychiatric disorders with dyskinesias, such as Huntington's disease or Gilles de la Tourette's syndrome; or for ballism or hemiballism; childhood psychoses or apparently allied conditions marked by severe agitation or aggressive behavior; miscellaneous medical indications, notably nausea and vomiting, or intractable hiccups.
Additionally, continuous long-term use of neuroleptics is indicated in many psychotic disorders, such as (for more than six months) (i) primary indications such as Schizophrenia, Paranoia.sup.a,b, Childhood psychoses, some degenerative or idiopathic neuropsychiatric disorders (notably, Huntington's disease and Gilles de la Tourette's syndrome); (ii) secondary indications such as extremely unstable manic-depressive or other episodic psychoses (unusual), otherwise unmanageable behavior symptoms in dementia, amentia, or other brain syndromes; and (iii) questionable indications such as chronic characterological disorders with schizoid, "borderline," or neurotic characteristics; substance abuse; or antisocial behavior, recurrent mood disorders. See, e.g., Baldessarini, Chemotherapy in Psychiatry, Revised and Enlarged Edition, Harvard University Press, Cambridge, Mass., (1985), the contents of which is entirely incorporated herein by reference.
Neuroleptics are also referred to as neuroplegics, psychoplegics, psycholeptics, antipsychotics and major tranquilizers, but are sometimes distinguished from non-neuroleptic anti-psychotics. Neuroleptics have recently been characterized as an agent that produces sedative or tranquilizing effects, and which also produces motor side effects, such as catalepsy or extrapyramidal symptomatology. Nonlimiting representative examples of neuroleptics include phenothiazine derivatives (e.g., chlorpromazine); thioxanthine derivatives (e.g., thiothixene); butyrophenone derivatives e.g., haloperidol); dihydroindolone (e.g., molindone); dibenzoxazepine derivatives (e.g., loxapine); and "atypical" neuroleptics (e.g., sulpiride, remoxipiride pimozide and clozapine). See Berstein Clinical Pharmacology Littleton, Mass. :PSG Publishing (1978); Usdin et al Clinical Pharmacology in Psychiatry New York:Elsevier North-Holland (1981); and Baldessarini, supra, (1985); and , which references are herein entirely incorporated by reference.
The term "atypical neuroleptics" has been used to describe antipsychotic neuroleptics that produce few or no extrapyramidal side effects and which do not cause catalepsy in animals (See, e.g., Picket et al, Arch. Gen. Psychiatry 49:345 (May 1992). Alternatively, atypical neuroleptics, such as clozapine, have been described as those neuroleptics which have a higher affinity for D.sub.4 and D.sub.1 sites than for D.sub.2 sites (See, e.g., Davis et al Amer. J. Psych. 148:1474, 1476 (November 1991).
The long term use of all known anti-psychotics, such as neuroleptics or non-neuroleptic antipsychotics, has resulted in serious side effects, as present in Table I, such as persistent and poorly reversible motoric dysfunctions (e.g., tardive dyskinesia) in a significant number of patients. These side effects are especially prevalent in geriatric populations, and adequate pharmacological treatment of these debilitating morotic dysfunctions is not currently available. This problem has severely limited the long-term, clinical administration of these agents.
TABLE I__________________________________________________________________________Neurological Side Effects of Neuroleptic-Antipsychotic Drugs Period ofReaction Features maximum risk Proposed mechanism Treatment__________________________________________________________________________Acute dystonia Spasm of muscles of 1-5 days Dopamine excess? Antiparkinsonism agents are tongue, face, neck, Acetylcholine excess? diagnostic and curative back; may mimic (i.m. or i.v., then p.o.) seizures; not hystericalParkinsonism Bradykinesia, rigidity, 5-30 days Dopamine blockade Antiparkinsonism agents variable tremor, mask- (rarely (p.o); dopamine agonists facies, shuffling gait persists) risky?Akathisia Motor restlessness; 5-60 days Unknown Reduce dose or change drug patient may experience (commonly low doses of propranolol; anxiety or agitation persists) antiparkinsonism agents or or benzodiazepines may helpTardive Oral-facial dyskinesia; 6-24 months Dopamine excess? Prevention best; treatmentdyskinesia choreo-athetosis, some- (worse on unsatisfactory; slow spontaneous times irreversible, withdrawal) remission rarely progressive"Rabbit" Perioral tremor (late Months or Unknown Antiparkinsonism agents; reducesyndrome parkinsonism variant?); years dose of neuroleptic usually reversibleMalignant Catatonia, stupor, Weeks Unknown Stop neuroleptic; antiparkinsonismsyndrome fever, unstable pulse agents usually fail; bromocriptine and blood pressure; often helps; dantrolene variable; myoglobinemia; can general supportive care crucial be fatal__________________________________________________________________________ .sup.a There may be an increased risk of hypotension on interacting high doses of propranolol with some antipsychotic agents; clonidine may also b effective at doses of 0.2-0.8 mg/day, but carries a high risk of hypotension (Zubenko et al., Psychiatry Res. 11: 143, 1984).
In addition, clozapine, although apparently capable of producing less motor side effects, can cause irreversible, potentially fatal agranulocytosis in a minority of patients administered the drug. Such serious side effects limit the use of clozapine to patients who are resistant to treatment with other neuroleptics.
Antipsychotics have a variety of significant pharmacological effects, e.g., as presented in the following Tables II and III.
TABLE II__________________________________________________________________________Comparative Pharmacology of Neuroleptics Phenothiazine Thioxanthene ButyrophenoneAlkaloid Derivative Derivative DerivativePharmacologic Actions Chlorpromazine Thiothixene Haloperidol__________________________________________________________________________Antipsychotic Yes++ Yes++ Yes++++Antiemetic Yes+++ Not tested Yes+++Hypothermia Yes+ Yes+ NoHypotension Yes++ Yes+++ +Parkinsonism Yes++ Yes+ Yes++++Antiadrenergic Yes++ Yes+++ +Anticholinergic Yes+ Yes+ NegligibleAntihistaminic Yes+ Negligible NegligibleReleases NE, DA No No NoBlocks DA Yes++ Yes+ Yes++++Blocks NE Yes++ Yes+++ Yes+Central sympathetic Yes++ Yes+ Yes+++suppressant__________________________________________________________________________ Chlorpromazine, thiothixene, and haloperidol decrease the functional availability of dopamine (DA) and norepinephrine (NE) by blocking the dopamine receptor sites in the basal ganglia and norepinephrine receptor sites in thalamic and hypothalamic areas. Reserpine simply reduces the concentrations of norepinephrine and dopamine in these areas. Both of these actions result in suppression of central sympathetic activity. + .fwdarw. ++++ indicate, from very weak to very strong effects.
TABLE III______________________________________Comparative Pharmacology of AntipsychoticsExtrapyramidal AdrenergicDrug Sedation Blockage Reaction______________________________________Chlorpromazine High Moderate to high ModerateChlor- High High Low to moderateprothixeneHaloperidol Low Low HighMolindone Moderate Moderate Moderate to highLoxapine High Low to moderate High______________________________________
See Ebadi, PHARMACOLOGY, Little, Brown and Co., Boston, 61-65 (1985); Cattabeni et al Adv. Biochem. Psychopharmacology 24:275 (1980). Baldessarini, supra, which references are herein incorporated entirely by reference.
However, despite the face that thousands of neurolepticor antipsychotic-type compounds have been synthesized and reported in the literature, such compounds which lack serious side effects and which have sufficient pharmacological activity, have not been disclosed.
Alternative to dopamine receptor GPRs, as presented above, other neuroreceptor GPRs are involved in neurological pathologies, and drugs such as neuroreceptor GPR binding agents, presently used for treating these pathologies, also suffer from similar side effects as those of neuroleptics, as presented above.
Other GPRs are also involved in receptor-related pathologies, such as hormone related GPRs involved in endocrine related pathologies,
Accordingly, there is a need to provide G-protein coupled receptor binding agents, including neuroreceptor and endocrine receptor GPRs, which do not produce such deleterious and debilitating side effects as those produced by known agents, such as neuroleptics, which can be used for therapy or diagnosis of GPR related pathologies.
Citation of documents herein is not intended as an admission that any of the documents cited herein is pertinent prior art, or an admission that the cited documents are considered material to the patentabilty of the claims of the present application. All statements as to the date or representations as to the contents of these documents are based on the information available to the applicant and does not constitute any admission as to the correctness of the dates or contents of these documents.
SUMMARY OF THE INVENTION
It is therefore an object of the present invention to overcome one or more deficiencies found in the related art.
It is another object of the present invention to provide non-naturally occurring synthetic, isolated and/or recombinant GPR polypeptides which are fragments, consensus fragments and/or sequences having conservative amino acid substitutions, of at least one transmembrane domain of at least one G-protein coupled receptor, which polypeptides have been discovered to have receptor-like functional binding sites of neuroreceptor and endocrine GPRs, such that GPR polypeptides of the present invention may bind GPR ligands, or which may also modulate, quantitatively or qualitatively, GPR ligand binding to GPRs.
In is still another object of the present invention to provide GPR polypeptides and compositions that have only partially helical structures, in contrast to known characterized transmembrane domains of GPRs, such as, but not limited to, GPR transmembrane domains I-VII.
it is yet another object of the present invention to provide synthetic or recombinant GPR polypeptides, conservative substitution derivatives thereof, antibodies, anti-idiotype antibodies, compositions and methods that can be used as potential modulators of G-protein coupled receptor function, by binding to GPR ligands or modulate GPR ligand binding, due to their expected biological properties, which may be used in diagnostic, therapeutic and/or research applications.
It is a further object of the present invention is to provide synthetic, isolated or recombinant polypeptides which are designed to inhibit or mimic various GPRs or fragments thereof, as receptor types and subtypes.
According to one aspect of the present invention, a synthetic or recombinant GPR polypeptide is provided that comprises a GPR amino acid sequence of, e.g., at least 5, 10, 15 or 20 amino acids, substantially corresponding to at least one transmembrane domain, or fragment and/or consensus peptide thereof, of a G-protein coupled receptor, wherein at least 20 amino acids are preferred. In a preferred embodiment, the polypeptide is (a) chemically synthesized and/or (b) obtained from a recombinant host cell or organism which expresses a recombinant nucleic acid encoding a GPR polypeptide, as defined herein.
In another preferred embodiment, the transmembrane domain is selected from at least one of TM1, TM2, TM3, TM4, TM5, TM6 or TM7, corresponding to transmembrane domains I, II, III, IV, V, VI and VII, respectively, of a GPR. In another preferred embodiment, the transmembrane domain is a dopamine receptor transmembrane domain selected from the group consisting of at least one of a D.sub.1, D.sub.2, D.sub.3, D.sub.4 and D.sub.5 dopamine receptor transmembrane domain. The transmembrane domain, e.g., may be selected from at least one of D.sub.2 receptor transmembrane domains III or V. In still another preferred embodiment, the GPR polypeptide amino acid sequence substantially corresponding to an amino acid sequence contained in at least one of FIG. 2 (SEQ ID NO:2), FIG. 3 (SEQ ID NO:3) or FIG. 5 (SEQ ID NO:5).
In another aspect of the present invention, a GPR composition is provided, comprising a GPR polypeptide, or a pharmaceutically acceptable ester, ether, sulfate, carbonate, malate, glucuronide or salt thereof, the composition further comprising a pharmaceutically acceptable carrier and/or diluent.
In still another aspect of the present invention, a method is provided for treating a subject suffering from a disease state involving a qualitative or quantitative pathological abnormality of a GPR protein or a biological molecule functionally associated therewith. Such biological molecule may be a membrane cytoplasmic protein, lipid, carbohydrate, saccharide, nucleoside or nucleotide mono-, di-, or tri-phosphate, an enzyme, a cofactor, a nucleic acid, a neurotransmitter, an ion, a carrier, a cell receptor, or any combination thereof.
In a preferred embodiment, the GPR protein is a dopamine receptor and the abnormality involves a dopamine related pathology, wherein the method comprises administering an effective dopamine receptor modulating amount of a GPR polypeptide of the present invention. In another preferred embodiment, the transmembrane domain is a D.sub.2 dopamine receptor domain and the disease state is a psychiatric disorder, such as schizophrenia or schiz affective disorder (see American Psychiatric Association, Revised Manual of Diagnostic and Statistical Criteria for Psychiatric Disorders (DSM-III-R), American Psychiatric Assoc. Press, Washington, DC (1989)).
In another preferred embodiment, the GPR composition is administered as a pharmaceutical composition to provide a GPR polypeptide in an amount ranging from about 0.01 .mu.g to 100 mg/kg, and also preferably, about 10 .mu.g to 10 mg/kg. In another preferred embodiment, the administering is by oraal intravenous, intramuscular, parenteral or topical administration, including mucosal administration to the nasal mucosa or the oral mucosa, by aerosol, nebulizer or drop administration as non-limiting examples.
Other objects of the invention will be apparent to skilled practitioners from the following detailed description and examples relating to the present invention.





BRIEF DESCRIPTION OF THE FIGURES
FIG. 1 is the amino acid sequence of a control peptide (SEQ ID NO:1), which is hydrophobic in its properties, but does not correspond to a known GPR transmembrane domain.
FIG. 2 represents the amino acid sequence of a GPR transmembrane polypeptide, polypeptide II (SEQ ID NO:2), which corresponds to a portion of the dopamine D.sub.2 receptor transmembrane segment III.
FIG. 3 represents the amino acid sequence of a transmembrane polypeptide, polypeptide III (SEQ ID NO:3), norresponding to a consensus peptide of the dopamine D.sub.2 receptor transmembrane domains I-VII.
FIG. 4 represents the amino acid sequence of a consensus sequence of transmembrane domains that is shortened to be less than the length required to span a lipid bilayer.
FIG. 5 represents a consensus amino acid sequence of transmembrane domain as a consensus peptide between dopamine receptors D.sub.1 and D.sub.2,
FIG. 6 is a representation of a circular dichroism spectrum of a solution of the consensus polypeptide III (SEQ ID NO: 3) of FIG. 3.
FIG. 7 is a graphical representation of radioligand binding assay data comparing control polypeptide II (SEQ ID NO:1) of FIG. 1, labeled as "II" and consensus polypeptide I (SEQ ID NO: 3 of FIG. 3, labeled as "I".
FIG. 8A-G are a comparison listing of amino acid sequences of transmembrane domains and adjacent amino acid sequences of representative GPRs (SEQ ID NOS:6-79).





DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention relates to G-protein coupled receptor (GPR) polypeptides which can be used to mimic naturally occurring or isolated GPRs, or to modulate the binding of GPR ligands to GPRs, such as inhibition or enhancement of binding. GPR polypeptides of the present invention can include GPR transmembrane domain fragments and/or consensus peptides thereof, of at lease 4-10 amino acids in length, and/or corresponding sequences having conservative amino acid substitutions as "substitution peptides", wherein the GPR polypeptide binds a GPR ligand or modulates the binding of a GPR ligand to a GPR in vitro, in vivo or in situ.
GPR polypeptides of the present invention can be synthesized or recombinantly produced, or optionally purified, to provide commercially useful amounts of GPR polypeptides for use in therapeutic, diagnostic or research applications, according to known method steps, see, e.g., Ausubel et al, eds. Current Protocols in Molecular Biology, Wiley Interscience, N.Y., (1987, 11992); and Sambrook et al, Molecular Cloning, A Laboratory Manual, 2nd edition, Vols. 1-3, Cold Spring Harbor Press, (1989), which references are herein entirely incorporated by reference.
Additionally, GPR polypeptides according to the present invention can be used to generate polyclonal and/or monoclonal antibodies, anti-idiotype antibodies thereto, or fragments thereof, which may used for diagnostic and/or therapeutic applications, according to known method steps, see, e.g., Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Press (1988), which is herein entirely incorporated by reference.
GPR polypeptides, anti-GPR antibodies or anti-idiotype antibodies (or fragments thereof) to GPR polypeptides have been unexpectedly discovered to quantitatively or qualitatively modulate G-protein coupled receptors, such that binding of GPR polypeptides or anti-idiotype antibodies (or fragments thereof) to G-protein coupled receptor ligands may be used for diagnostic research or therapeutic applications of the present invention. Such GPR polypeptides, antibodies or anti-idiotype antibodies of the present invention may therefore be used as modulators of G-protein coupled receptors, such as neuroreceptors or endocrine receptors, as non-limiting examples.
Binding of such GPR polypeptides, (including GPR fragments, consensus peptides, substitution derivatives and anti-idiotype antibody fragments) of the present invention may be used to treat symptoms of, and provide diagnosis and treatment for, pathologies related to GPRs. Such pathologies have been found to correlate with symptoms occurring in neurological. viral or endocrine pathologies. D.sub.2 receptor-related psychotic disorders, including schizophrenia, now treated with neuroleptics, is a non-limiting example thereof.
The use of synthetic or recombinant GPR polypeptides of the present invention can be preferable to the use of known drugs that bind G-protein coupled receptors, such as neuroleptics that bind or inhibit the biological effect of binding to neuroreceptors as a non-limiting example. Such polypeptides are expected to have significantly less side effects than presently used drugs presently used for inhibiting such receptor binding including neuroleptics, as they would structurally mimic naturally occuring GPRs and/or modulate ligand binding. Thus, GPR polypeptides are expected to have reduced side effects attributable to known foreign compound drugs, with less immunogenicity, and reduced potential for motoric side effects (e.g., extrapyramidal symptoms and/or tardive dyskinesia).
The present invention is also related to the production, by chemical synthesis or recombinant DNA technology, of GPR polypeptides, preferably as small as possible while still retaining sufficiently high affinity or interaction with G-protein coupled receptors to modulate, such as to inhibit or to enhance, binding to such receptors by GPR ligands.
GPR polypeptides of the present invention may include 5-10 to 50-150 amino acid fragments, consensus sequences or substitution sequences of GPRs, e.g., as presented in FIG. 8A-G (SEQ ID NOS:6-79) including, but not limited to, multiple dopamine receptors, cAMP receptors, adenosine receptors, .beta.-adrenergic receptors, muscarinic acetylcholine receptors, .alpha.-adrenergic recepnors, serotonin receptors (5-HT), histamine H2 receptors, thrombin receptors, kinin receptors, follicle stimulating hormone receptors, opsins and rhodopsins, odorant receptors, cytomegalovirus GPRs, adenosine A2 receptors, dopamine receptor, histamine H2 receptors, octopanmine receptors, N-formyl receptors, anaphylatoxin receptors, thromboxane receptors, IL-8 receptors, platelet activating factor receptors, endothelin receptors, bombesin gastrin releasing peptide receptor, neuromedin B preferring bombesin receptors, vasoactive intestinal peptides, neurotensin receptors, bradykinin receptors, thyrotropin-releasing hormone receptors, substance Preceptors, neuromedin K receptors, drenal angiotensen II type I receptors, mas oncogene (angiotensin) receptors lutropin-choriogonadotropin receptors, thyrotropin receptors, follicle stimulating hormone receptors, cannabinoid receptors, glucocorticoid-induced receptors, endothelial cell GPRs, testis GPRs, and thoracic aorta GPRs, and homologs thereof having a homology of at least 80% with at least one of transmembrane domains 1-7, as described herein. See, e.g., Probst et al DNA and Cell Biology 11:1-20(1992), which is entirely incorporated herein by reference.
Accordingly, a "G-protein coupled receptor polypeptide" or "GPR polypeptide" of the present invention includes polypeptides having a "GPR amino acid sequence" which substantially corresponds to at least one 10 to 50 amino acid fragment and/or consensus sequence of a known GPR or group of GPRs, wherein the GPR polypeptide has homology of at least 80%, such as 81, 82, 83, 84, 85, 86, 87, 88, 89 90 91, 92 93, 94, 95, 96, 97, 98, 99 or 100% homology, while maintaining GPR modulating activity, wherein a GPR polypeptide of the present invention is not naturally occurring or is naturally occurring but is in a purified or isolated form which does not occur in nature. Preferably, a GPR polypeptide of the present invention substantially corresponds to a transmembrane domain of a GPR or group of GPRs as a consensus sequence.
Also preferred are GPR polypeptides wherein the GPR amino acid sequence is 4-10 to 50 amino acids in length, such as 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140 or 150 amino acids, or any range therein.
An amino acid or nucleic acid sequence of a GPR polypeptide of the present invention is said to "substantially correspond" to another amino acid or nucleic acid sequence, respectively, if the sequence of amino acids or nucleic acid in both molecules provides polypeptides having biological activity that is substantially similar, qualitatively or quantitatively, to the corresponding fragment of at least one GPR transmembrane domain, or which may be synergistic when two or more transmembrane domains, consensus sequences or homologs thereof are present.
Additionally or alternatively, such "substantially corresponding" sequences of GPR polypeptides include conservative amino acid or nucleotide substitutions, or degenerate nucleotide nodon substitutions wherein individual amino acid or nucleotide substitutions are well known in the art.
Alternatively or additionally, substantially corresponding refers to GPR polypeptides having amino acid sequences having at least 80% homology or identity to an amino acid sequence of SEQ ID NO:l, such as 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% homology or identity.
Accordingly, GPR polypeptides of the present invention, or nucleic acid encoding therefor, include a finite set of substantially corresponding sequences as substituuion peptides or polynucleotides which can be routinely obtained by one of ordinary skill in the art, without undue experimentation, based on the teachings and guidance presented herein. For a detailed description of protein chemistry and structure, see Schulz, G. E. et al., Principles of Protein Structure, Springer-Verlag, New York, 1978, and Creighton, T. E., Proteins: Structure and Molecular Properties, W. H. Freeman & Co., San Francisco, 1983, which are hereby incorporated by reference. For a presentation of nucleotide sequence substitutions, such as codon preferences, see Ausubel et al, supra, at .sctn..sctn.A.1.1-A.1.24, and Sambrook et al, supra, at Appendices C and D.
Conservative substitutions of a GPR polypeptide of the present invention includes a variant wherein at least one amino acid residue in the polypeptide has been conservatively replaced by a different amino acid. Such substitutions pruferably are made in accordance with the following list as presented in Table IV, which substitutions may be determined by routine experimentation provide modified structural and functional properties of a synthesized polypeptide molecule, while maintaining the receptor binding, inhibiting or mimicking biological activity, as determined by known GPR receptor activity assays.
TABLE IV______________________________________Original ExemplaryResidue Substitution______________________________________Ala Gly;SerArg LysAsn Gln;HisAsp GluCys SerGln AsnGlu AspGly Ala;ProHis Asn;GlnIle Leu;ValLeu Ile;ValLys Arg;Gln;GluMet Leu;Tyr;IlePhe Met;Leu;TyrSer ThrThr SerTrp TyrTyr Trp;PheVal Ile;Leu______________________________________
Alternatively, another group of substitutions of GPR polypeptides of the present invention are those in which at least one amino acid residue in the protein molecule has been removed and a different residue inserted in its place according to the following Table V. The types of substitutions which may be made in the protein or peptide molecule of the present invention may be based on nalysis of the frequencies of amino acid changes between a homologous protein of different species, such as those presented in Table 1-2 of Schulz et al., .Supra and FIGS. 3-9 of Creighton, supra. Based on such an analysis, alternative conservative substitutions are defined herein as exchanges within one of the following five groups:
TABLE V
1. Small aliphatic, nonpolar or slightly polar residues: Ala, Ser, Thr (Pro, Gly);
2. Polar, negatively charged residues and their amides: Asp, Asn, Glu, Gln;
3. Polar, positively charged residues: His, Arg, Lys;
4. Large aliphatic, nonpolar residues: Met, Leu, Ile, Val (Cys); and
5. Large aromatic residues: Phe, Tyr, Trp.
The three amino acid residues in parentheses above have special roles in protein architecture. Gly is the only residue lacking any side chain and thus imparts flexibility to the chain. This however tends to promote the formation of secondary structure other than .alpha.-helical. Pro, because of its unusual geometry, tightly constrains the chain. It generally tends to promote .beta.-turn-like structures, although in some cases Cys can be capable of participating in disulfide bond formation which is important in protein folding. Note the Schulz et al. would merge Groups 1 and 2, above. Note also that Tyr, because of its hydrogen bonding potential, has significant kinship with Ser, and Thr, etc.
Conservative amino acid substitutions according to the present invention, e.g., as presented above, are known in the art and would be expected to maintain biological and structural properties of the polypeptide after amino acid substitution. Most deletions and insertions, and substitutions according to the present invention are those which do not produce radical changes in the characteristics of the protein or peptide molecule. "Characteristics" is defined in a non-inclusive manner to define both changes in secondary structure, e.g. .alpha.-helix or .beta.-sheet, as well as changes in physiological activity, e.g. in receptor binding assays.
However, when the exact effect of the substitution, deletion, or insertion is to be confirmed one skilled in the art will appreciate that the effect of the substitution or substitutions will be evaluated by routine screening assays, either immunoassays or bioassays to confirm biological activity, such as receptor binding or modulation of ligand binding to the corresponding GPR. See, e.g., Maranges et al., eds., for example, a substituted polypeptide mypically is made by site-specific mutagenesis of the peptide molecule-encoding nucleic acid, expression of the mutant nucleic acid in recombinant cell culture, and, optionally, purification from the cell culture, for example, by immunoaffinity chromatography using a specific antibody on a chemically derivatized column or immobilized membranes or hollow fibers (to absorb the mutant by binding to at least one epitope).
A preferred use of this invention is the production, by chemical or recombinant DNA technology, of GPR polypeptides, preferably as small as possible while still retaining sufficiently high affinity for binding to, or association with, GPRs. By production of GPR polypeptides including smaller fragments or variants of such transmembrane domains, one skilled in the art, using known binding and inhibition assays, can readily identify the GPR polypeptides capable of binding minimizing or modulating G-protein coupled receptors using known methods. Non-limiting examples of fragments of GPRs to be used as GPR polypeptides or as a basis for consensus sequences thereof for GPR polypeptides, are presented in FIGS. 2-5 and FIG. 8A-G, wherein fragments or consensus sequences of 10 to 50 amino acids of at least one sequence of FIGS. 2-5 or corresponding to at least one transmembrane domain or domains 1-7 listed in FIG. 8A-G (SEQ ID NOS:6-79) are encompassed by the present invention, such as at least one transmembrane domain of one or more GPRs, such as a cAMP receptor (1), adenosine receptors (2-3); muscarinic acetylcholine receptors (4- 8); human adrenergic receptors (9-11, 14-16, 19-25, 28); adrenergic receptors (9-28); human thrombin receptor (31); endothelin receptors (35-36), bombesin receptors (37-38), endocrine receptors (48-50), rhodopsin (51) . opsins (52-54), odorant receptors (55-64), and cytomegalovirus GPRs (72-54), as non-limiting examples, wherein ("#") refers to the listed sequences in FIG. 8A-G.
Accordingly, GPR polypeptides may include consensus sequences and/or fragments of at least one of transmembrane domain 1-7 of one or more GPRs as presented in FIGS. 2-5 (SEQ ID NO:2-5) or FIG. 8A-G. (SEQ ID NOS:6-79) or homologs thereof, which GPR polypeptides do not occur naturally, and/or which are provided in an isolated and/or purified form not found in nature.
Consensus peptides of GPR polypeptides of the present invention may include peptides which are distinct from known GPR sequences in critical structural features, but which are derived from consensus sequences of homologous GPR transmembrane domains 1-7, e.g., as presented in FIG. 8A-G (SEQ ID NOS:6-79). Such consensus peptides may be derived by molecular modeling, optionally combined with hydrophobicity analysis and/or fitting to model helices, as non-limiting examples. Such modeling can be accomplished according to known method steps using known modeling algorithms, such as, but not limited to, ECEPP, INSIGHT, DISCOVER, CHEM-DRAW, AMBER, FRODO and CHEM-X. Such algorithms compare transmembrane domains between related G-protein coupled receptors, determine probable energy-miminized structures and define alternative consensus polypeptide fragments.
Such consensus peptides or fragments of GPRs may then be synthesized or produced recombinantly, in order to provide GPR polypepnides according to the present invention which mimic, modulate or inhibit binding of ligands to G-protein coupled receptors. GPR ligands, in the context of the present invention, refer to biological molecules that bind GPRs in vitro, in situ or in vivo, and may include hormones, neurotransmitters, viruses or receptor binding domains, thereof, opsins, rhodopsins, nucleosides, nucleotides, coagulation cascade factors, odorants or pheremones, toxins, colony stimulating factors, platelet activating factors, neuroactive peptides, neurohumors, or any biologically active compounds, such as drugs or synthetic or naturally occurring compounds.
The following non-limiting examples of consensus peptides of GPRs of the present invention are provided by way of guidance and not by way of limitation. In GPR polypeptides of the present invention, one or more, preferably 4-10, Asp and/or Lys residues may additionally be incorporated at the carboxy and/or amino terminal ends in order to provide expected helix forming effects of the helix dipole effect, e.g., as described in Baldwin et al Biochem. 28:2130 (1989); Baldwin et al Proc. Nat'l Acad. Sci. USA 84:8898 (1987); and Baldwin et al Proc. Nat'l Acad. Sci. USA 86:5286 (1989), which references are entirely incorporated herein by reference.
As a non-limiting example of GPR polypeptide of the present invention, dopamine receptor transmembrane fragments of D.sub.2 transmembrane domain (e.g., domain III) as presented in FIG. 2 (SEQ ID NO:2) or a consensus sequence as presented in FIG. 3 (SEQ ID NO:3), e.g., of D.sub.2 domains I-VII. Additionally or alternatively a consensus sequence may include less than 20 amino acids, such as 15 amino acids corresponding to a transmembrane domain, such as a D.sub.2 receptor domain, as presented in FIG. 4 (SEQ ID NO:4) as polypeptide IV, which is smaller than the length required by spanning an average lipid bilayer of a cell membrane.
However, in the context of the present invention, GPR polypeptides of greater than 15-20 amino acids are preferred such that the GPR polypeptides are able to span the lipid bilayer.
Another non-limiting example of a GPR polypeptide using dopamine receptor transmembrane domains is a consensus sequence of two or more GPR receptors, such as the dopamine D.sub.1 and D.sub.2 receptors. A non-limiting example of such a consensus GPR polypeptide is presented in FIG. 5 (SEQ ID NO:5).
Additionally, modified amino acids or chemical derivatives of amino acids of consensus or fragments of GPRs proteins, according to the present invention may be provided, which polypeptides contain additional chemical moieties or modified amino acids not normally a part of the protein. Covalent modifications of the peptide are thus included within the scope of the present invention. Such modifications may be introduced into a GPR polypeptide by reacting targeted amino acid residues of the polypeptide with an organic derivatizing agent that is capable of reacting with selected side chains or terminal residues. The following examples of chemical derivatives are provided by way of illustration and not by way of limitation.
Aromatic amino acids may be replaced with D- or L-naphylalanine, D- or L-Phenylglycine, D- or L-2-thieneylalanine, D- or L-1-, 2-, 3- or 4-pyreneylalanine, D- or L-3-thieneylalanine, D- or L-(2-pyridinyl)-alanine, D- or L-(3-pyridinyl)-alanine, D- or L-(2-pyrazinyl)-alanine, D- or L-(4-isopropyl)-phenylglycine, D-(trifluoromethyl)-phenylglycine, D-(trifluoromethyl)-phenylalanine, D-p-fluorophenylalanine, D- or L-p-biphenylphenylalanine, D- or L-p-methoxybiphenylphenylalanine, D- or L-2-indole(alkyl)alanines, and D- or L-alkylainines where alkyl may be substituted or unsubstituted methyl, ethyl, propyl, hexyl, butyl, pentyl, isopropyl, iso-butyl, sec-isotyl, iso-pentyl, non-acidic amino acids, of C1--C20.
Acidic amino acids call be substituted with non-carboxylate amino acids while maintaining a negative charge, and derivatives or analogs thereof, such as the non-limiting examples of (phosphono)alanine, glycine, leucine, isoleucine, threonine, or serine; or sulfated (e.g., -SO.sub.3 H) threonine, serine, tyrosine.
Other substitutions may include unnatural hyroxylated amino acids may made by combining "alkyl" (as defined and exemplified herein) with any natural amino acid. Basic amino acids may be substituted with alkyl groups at any position of the naturally occurring amino acids lysine, arginine, ornithine, citrulline, or (guanidino)-acetic acid, or other (guanidino)alkyl-acetic acids, where "alkyl" is define as above. Nitrile derivatives (e.g., containing the CN-moiety in place of COOH) may also be substituted for asparagine or glutamine, and methionine sulfoxide may be substituted for methionine. Methods of preparation of such peptide derivatives are well known to one skilled in the art.
In addition, any amide linkage in any of the GPR polypeptides can be replaced by a ketomethylene moiety, e.g. (--C(.dbd.O)-- CH.sub.2 --) for (--(C.dbd.O)--NH--). Such derivatives are expected to have the property of increased stability to degradation by enzymes, and therefore possess advantages for the formulation of compounds which may have increased in vivo half lives, as administered by oral, intravenous, intramuscular, intraperitoneal, topical, rectal, intraocular, or other routes.
In addition, any amino acid representing a component of the said peptides can be replaced by the same amino acid but of the opposite chirality. Thus, any amino acid naturally occurring in the L-configuration (which may also be referred to as the R or S, depending upon the structure of the chemical entity) may be replaced with an amino acid of the same chemical structural type, but of the opposite chirality, generally referred to as the D- amino acid but which can additionally be referred to as the R- or the S-, depending upon its composition and chemical configuration. Such derivatives have the property of greatly increased stability co degradation by enzymes, and therefore are advantageous in the formulation of compounds which may have longer in vivo half lives, when administered by oral, intravenous, intramuscular, intraperitoneal, topical, rectal, intraocular, or other routes.
Additional amino acid modifications of amino acids of GPR polypeptides of to the present invention may include the following: Cysteinyl residues may be reacted with alpha-haloacetates (and corresponding amines), such as 2-chloroacetic acid or chloroacetamide, to give carboxymethyl or carboxyamidomethyl derivatives. Cysteinyl residues may also be derivatized by reaction with compounds such as bromotrifluoroacetone, alpha-bromo-beta-(5-imidozoyl)propionic acid, chloroacetyl phosphate, N-alkylmaleimides, 3-nitro-2-pyridyl disulfide, methyl 2-pyridyl disulfide, p-chloromercuribenzoate, 2-chloromercuri-4-nitrophenol, or chloro-7-nitrobenzo-2-oxa-1,3-diazole.
Histidyl residues may be derivatized by reaction with compounds such as diethylprocarbonate e.g., at pH 5.5-7.0 because this agent is relatively specific for the histidyl side chain, and para-bromophenacyl bromide may also be used; e.g., where the reaction is preferably performed in 0.1M sodium cacodylate at pH 6.0.
Lysinyl and amino terminal residues may be reacted with compounds such as succinic or other carboxylic acid anhydrides. Derivatization with these agents is expected to have the effect of reversing the charge of the lysinyl residues. Other suitable reagents for derivatizing alpha-amino-containing residues include compounds such as imidoesters/e.g., as methyl picolinimidate; pyridoxal phosphate; pyridoxal; chloroborohydride; trinitrobenzenesulfonic acid; O-methylisourea; 2,4 pentanedione; and transaminase-catalyzed reaction with glyoxylate.
Arginyl residues may be modified by reaction with one or several conventional reagents, among them phenylglyoxal, 2,3-butanedione, 1,2-cyclohexanedione, and ninhydrin according to known method steps. Derivatization of arginine residues requires that the reaction be performed in alkaline conditions because of the high pKa of the guanidine functional group. Furthermore, these reagents may react with the groups of lysine as well as the arginine epsilon-amino group.
The specific modification of tyrosyl residues per se is well-known, such as for introducing spectral labels into tyrosyl residues by reaction with aromatic diazonium compounds or tetranitromethane. N-acetylimidizol and tetranitromethane may be used to form O-acetyl tyrosyl species and 3-nitro derivatives, respectively.
Carboxyl side groups (aspartyl or glutamyl) may be selectively modified by reaction with carbodiimides (R'-N-C-N-R') such as 1-cyclohexyl-3-(2-morpholinyl- (4-ethyl) carbodiimide or 1-ethyl-3-(4-azonia-4,4- dimethylpentyl) carbodiimide. Furthermore aspartyl and glutamyl residues may be converted to asparaginyl and glutaminyl residues by reaction with ammonium ions.
Glutaminyl and asparaginyl residues may be frequently deamidated to the corresponding glutamyl and aspartyl residues. Alternatively, these residues may be deamidated under mildly acidic conditions. Either form of these residues falls within the scope of the present invention.
Derivatization with bifunctional agents is useful for cross-linking the peptide to a water-insoluble support matrix or to other macromolecular carriers, according to known method steps. Commonly used cross-linking agents include, e.g., 1,1-bis(diazoacetyl)-2-phenylethane, glutaraldehyde, N-hydroxysuccinimide esters, for example, esters with 4-azidosalicylic acid, homobifunctional imidoesters, including disuccinimidyl esters such as 3,3'-dithiobis(succinimidylpropionate), and bifunctional maleimides such as bis-N-maleimido-1,8-octane. Derivatizing agents such as methyl-3-[(p-azidophenyl)dithio]propioimidateyieldphotoactivatable intermediates that are capable of forming crosslinks in the presence of light. Alternatively, reactive water-insoluble matrices such as cyanogen bromide-activated carbohydrates and the reactive substrates described in U.S. Pat. Nos. 3,969,287; 3,691,016; 4,195,128; 4,247,642; 4,229,537; and 4,330,440 (which are herein incorporated entirely by reference), may be employed for protein immobilization.
Other modifications of GPR polypeptides of the present invention may include hydroxylation of proline and lysine, phosphorylation of hydroxyl groups of seryl or threonyl residues, methylation of the alpha-amino groups of lysine, arginine, and histidine side chains (T. E. Creighton, Proteins: Structure and Molecule Properties, W. H. Freeman & Co., San Francisco, pp. 79-86 (1983)), acetylation of the N-terminal amine, methylation of main chain amide residues (or substitution with N-methyl amino acids) and, in some instances, amidation of the C-terminal carboxyl groups, according to known method steps.
Such derivatized moleties may improve the solubility, absorption, permeability across the blood brain barrier biological half life, and the like. Such moleties or modifications of GPR polypeptides may alternatively eliminate or attenuate any possible undesirable side effect of the protein and the like. Moleties capable of mediating such effects are disclosed, for example, in Remington's Pharmaceutical Sciences, 16th ed., Mack Publishing Co., Easton, Pa. (1980).
Such chemical derivatives of GPR polypeptides also may provide attachment to solid supports, including but not limited to, agarose, cellulose, hollow fibers, or other polymeric carbohydrates such as agarose, cellulose, such as for purification, generation of antibodies or cloning; or to provide altered physical properties, such as resistance to enzymatic degradation or increased binding affinity or modulation for GPRs, which is desired for therapeutic compositions comprising GPR polypeptides, antibodies thereto or fragments thereof. Such peptide derivatives are well-known in the art, as well as method steps for making such derivatives using carbodiimides active esters of N-hydroxy succinimmide, or mixed anhydrides, as non-limiting examples.
Variation upon consensus peptide sequences of GPR polypeptide of the present invention may also include: the addition of one, two, three, four, or five lysine, arginine or other basic residues added to the --COOH terminal end of the peptide; and/or one, two, three, four, or five glutamate or aspartate or other acidic residues added to the amino terminal end of the peptide, where "acidic" and "basic" are as defined herein. Such modifications are well known to increase the .alpha.-helical content of the peptide by the "helix dipole effect". They also can provide enhanced aqueous solubility of the peptide. See, e.g., Baldwin et al., supra.
As another non-limiting example of a GPR polypeptide of the present invention, serotonergic receptors (5-HT) consensus sequences may be determined using presently known 5-HT sequences and include, e.g., as consensus peptides of TM3, TM5 and TM7, respectively:
5-HT consensus (1) DDDDNIWSIFDWIGYLNSISMVIYTLFKKKK (SEQ ID NO:80)
5-HT consensus (2) DDDDNIWNIFSTIGYLNSISPVSVIMHIYGKKKK (SEQ ID NO:81)
5-HT consensus (3) DDDDGYSIYDTLVTFAINPVYITVFKKKK (SEQ ID NO:82)
Such non-naturally occurring consensus sequences may also be further modified according to known method steps to provide additional consensus peptides with substituted amino acids to increase or decrease .alpha.-helical propensity and/or solubility (e.g., hydrophilicity). As a non-limiting example, 5-HT consensus peptide (1) above may be modified according to the present invention to have increase helical propensity and increased aqueous solubility as follows:
5-HT consensus (4) DDDDNAWSAFDWALYLNSISMAIYTYAKKKK (SEQ ID 2 10:83),
wherein, e.g., smaller, non-polar residues replace either larger, more polar residues (e.g., Ala for Ile or Val) or larger aromatic residues (e.g., Ala for Phe).
Another non-limiting, illustrative example of consensus GPR polypeptides of the present invention are those for adrenergic receptors, are the following:
An example of the consensus GPR polypeptide for domain VII across all presently known adrenergic receptors is as follows:
adrenergic consensus (1) LFSFITWLGYANSSLNPIIYTTF (SEQ ID NO: 84)
An example of a consensus GPR polypeptide for domain V across all adrenergic receptors is as follows:
adrenergic consensus(2) VYTIYSSSWFFAPSLAIMVITYT (SEQ ID NO :85)
Examples of a consensus GPR polypeptide for domain III across all adrenergic receptors are as follows:
adrenergic consensus (3) IWLTSDIMSTSSILHNLCVISF (SEQ ID NO: 86)
An example of a consensus GPR polypeptide for domains III, V, and VII of all adrenergic receptors is as follows:
adrenergic consensus (4) IWSIFSSDIWGYAINHSSLAIMCPIVIYTV (SEQ ID NO: 87)
adrenergic consensus(5) IFTIFSSDIAVGYANHSSAAIMPIVIYSV (SEQ ID NO:88),
wherein variations and substitutions of amino acids may be made as described herein.
Non-limiting examples of consensus GPR polypeptides for transmembrane domain III across several or many, such as 1-500, or any range or value therein, G-protein receptors are as follows:
TM3-(1) YAIFVLYASAWLSFLNCPFIVTLNI (SEQ ID N0:96)
TM3-(2) YAIFVLYATAWLSFLNCPFIVTLNI(SEQ ID NO:97)
TM3-(3) YAIFVLYATAWLTFLNCPFIVTLNI(SEQ ID NO:98)
TM3-(4) YAIFVLYASAWLTFLNCPFIVTLNI(SEQ ID NO:99)
TM3-(5) WAIFVLYASAWLSFLNCPFIVTLNI(SEQ ID NO:100)
TM3-(6) WAIFVLYATAWLSFLNCPFIVTLNI (SEQ ID NO: 101)
TM3-(7) WAIFVLYATAWLTFLNCPFIVTLNI(SEQ ID NO:102)
TM3-(8) WAIFVLYASAWLTFLNCPFIVTLNI (SEQ ID NO: 103)
TM3-(9) YAVFVLYASAWLSFLNMPFIVTLNI(SEQ ID NO: 104)
TM3-(10) YAVFVLYATAWLSFLNMPFIVTLNI (SEQ ID NO: 105)
TM3-(11) YAVFVLYATAWLTFLNMPFIVTLNI (SEQ ID NO: 106)
TM3-(12) YAVFVLYASAWLTFLNMPFIVTLNI (SEQ ID NO: 107)
TM3-(13) YAIFVLYASAWLSFLNCVTASIPFIVTLNI (SEQ ID NO: 108)
TM3-(14) YAIFVLYASAWLSFLNCTSSIVVTASIVTLNI (SEQ ID NO: 109)
TM3-(15) YAIFVLYASAWLSFLNVTLNICTSSIV (SEQ ID NO: 110)
TM3-(16) YAIFVLYASAWLSFLNTASILNLMFIVTLNI (SEQ ID NO: 111)
TM3-(17) YAIFVLYASAWLSFLNMASILNLPFIVTLNI (SEQ ID NO: 112)
TM3-(18) YAIFVLYASAWLSFLNSGILLLAPFIVTLNI (SEQ ID NO: 113)
TM3-(19) YAIFVLYASAWLSFLNMSGILLLAPFIVTLNI (SEQ ID NO: 114)
TM3-(20) YAIFVLYASAWLSFLNSELSVYTLTVCPFIVTLNI (SEQ ID NO: 115)
TM3-(21) YAIFVTYASAWLS FLNMSELSVYTLTVPFIVTLNI (SEQ ID NO: 116)
TM3-(22) YAIFVLYASAWLASELSVYTLTVSFLNCPFIVTLNI (SEQ ID NO: 117)
TM3-(23) YAIFVLYASAWLASELSVYTLTVPFIVTLNI (SEQ ID NO: 118)
TM3-(24) YAIFVLYASAWLSFLASELSVYASELSSTLTTVNMPFIVTLNI (SEQ ID NO: 119)
TM3-(25) YAIFVLYASAWLSFLNGGEIALWSLCPFIVTLNI (SEQ ID NO: 120)
TM3-(26) YAIFVLYASAWLSFLNGGEIALWSLIVTLNI (SEQ ID NO: 121)
TM3-(27) YAIFVLYASAWLGGEIALWSLNCPFIVTLNI (SEQ ID NO: 122)
TM3-(28) YAIFVLYAGGEIALWSLSFLNCPFIVTLNI (SEQ ID NO: 123)
TM3-(29) YAIFVLYASAWLSFFFLLFGYLGNFLLNCPFIVTLNI (SEQ ID NO: 124)
TM3-(30) YAIFVLYASAWLFFFLLFGYLGNFLLPFIVTLNI (SEQ ID NO: 125)
TM3-(31) YAIFVLYASAWLSFLNTACFYVAITASLCFITEIALIPFIVTLNI (SEQ ID NO: 126)
TM3-(32) YAIFVLYASAWLTACFYVAITASLCFITEIALICPFIVTLNI (SEQ ID NO: 127)
TM3-(33) YAIFVLYATACFYVAITASLCFITEIALISFLNCPFIVTLNI (SEQ ID NO: 128)
TM3-(34) YAITACFYVAITASLCFITEIALIASAWLSFLNCPFIVTLNI (SEQ ID NO: 129)
TM3-(35) YAIFVLYATACFYVAIITEIALISAWLSFLNCPFIVTLNI (SEQ ID NO: 130)
TM3-(36) YAIFVLYASAWLSFLNACFYICLFAGVCFLIPFIVTLNI (SEQ ID NO: 131)
TM3-(37) YAIFVLYASAWNACFYICLFAGVMFLILSFLNCPFIVTLNI (SEQ ID NO:132)
TM3-(38) YAIFVLYFYICLFAGVCFLIASAWLSFLNCPFIVTLNI (SEQ ID NO: 133)
TM3-(39) YAIFVLYASVDAVNMFTSAWLSFLNCPFIVTLNI (SEQ ID NO: 134)
TM3-(40) YAIFSVDAVNMFTVLYASAWLSFLNCPFIVTLNI (SEQ ID NO: 135)
TM3-(41) YAIFVLYASAWLSVDAVNMFTSFLNCPFIVTLNI (SEQ ID NO: 136)
TM3-(42) YAIFVLYASAWLSFLNSVDAVNMFTPFIVTLNI (SEQ ID NO: 137)
TM3-(43) YAIFVLYASAWLSFLNCPFIVSVDAVNMFTTLNI (SEQ ID NO: 138)
TM3-(44) YAIFVLYASAWLSVDMFTSFLNCPFIVTLNI (SEQ ID NO: 139)
TM3-(45) YAISVDAVNMFTFVLYASAWLSFLNCPFIVTLNI (SEQ ID NO: 140)
TM3-(46) YAIFSLSVFSLLAIVLYASAWLSFLNCPFIVTLNI (SEQ ID NO: 141)
TM3-(47) YAIFVLYASLSVFSLLAISAWLSFLNCPFIVTLNI (SEQ ID NO: 142 )
TM3-(48) YAIFVLYASAWLSLSVFSLLAISFLNCPFIVTLNI (SEQ ID NO: 143 )
TM3-(49) YAIFVLYASAWLSFLSLSVFSLLAINCPFIVTLNI (SEQ ID NO: 144 )
TM3-(50) YAIFVLYASAWLSFLNPFSLSVFSLLAIIVTLNI (SEQ ID NO: 145 l )
TM3-(51) YAIFVLYATAWLTFLNCVTATIPFIVTLNI (SEQ ID NO: 146)
TM3-(52) YAIFVLYATAWLSFLNCTSSIVVTATIVTLNI (SEQ ID NO: 147)
TM3-(53) YAIFVLYATAWLSFLNVTLNICTTTIV (SEQ ID NO: 148)
TM3-(54) YAI FVLYATAWLTFLNTATILNLMFIVTLNI (SEQ ID NO: 149)
TM3-(55) YAIFVLYATAWLSFLNMATILNLPFIVTLNI (SEQ ID NO: 150)
TM3-(56) YAIFVLYATAWLTFLNSGILLLAPFIVTLNI (SEQ ID NO: 151)
TM3-(57) YAIFVLYASAWLTFLNMTGILLLAPFIVTLNI (SEQ ID NO: 152)
TM3-(58) YAIFVLYASAWLTFLNTELTVYTLTVCPFIVTLNI (SEQ ID NO: 153)
TM3-(59) YAIFVLYASAWLTFLNMTELTVYTLTVPFIVTLNI (SEQ ID NO: 154)
TM3-(60) YAIFVLYATAWLATELTVYTLTVTFLNCPFIVTLNI (SEQ ID NO: 155)
TM3-(61) YAIFVLYASAWLATELSVYTLTVPFIVTLNI (SEQ ID NO: 156)
TM3-(62) YAIFVLYATAWLSFLATELSVYASELSTTLTTVNMPFILNI (SEQ ID NO: 157)
TM3-(63) YAIFVLYATAWLSFLNGGEIALWTLCPFIVTLNI (SEQ ID NO: 158)
TM3-(64) YAIFVLYASAWLTFLNGGEIALWTLIVTLNI (SEQ ID NO: 159)
TM3-(65) YAIFVLYASAWLGGEIALWTLNCPFIVTLNI (SEQ ID NO: 160)
TM3-(66) YAIFVLYAGGEIALWTLSFLNCPFIVTLNI (SEQ ID NO: 161)
TM3-(67) YAIFVLYATAWLSFFFLLFGYLGNFLLNCPFIVTLNI (SEQ ID NO: 162)
TM3-(68) YAIFVLYATAWLFFFLLFGYLGNFLLPFIVTLNI (SEQ ID NO: 163)
TM3-(69) YAIFVLYATAWLTFLNTACFYVAITASLCFITEIALIPFIVTLNI (SEQ ID NO: 164)
TM3-(70) YAIFVLYATAWLTACFYVAITATLCFITEIALICPFIVTLNI (SEQ ID NO: 165)
TM3-(71) YAIFVLYATACFYVAITATLCFITEIALISFLNCPFIVTLNI (SEQ ID NO: 166)
TM3-(72) YAITACFYVAITASLCFITEIALIATAWLTFLNCPFIVTLNI (SEQ ID NO: 167)
TM3-(73) YAIFVLYATACFYVAIITEIALITAWLTFLNCPFIVTLNI (SEQ ID NO. 168)
TM3-(74) YAIFVLYASAWLTFLNACFYICLFAGVCFLIPFIVTLNI (SEQ ID NO: 169)
TM3-(75) YAIFVLYASAWNACFYICLFAGVMFLILTFLNCPFIVTLNI (SEQ ID NO: 170)
TM3-(76) YAIFVLYFYICLFAGVCFLIATAWLTFLNCPFIVTLNI (SEQ ID NO: 171)
TM3-(77) YAIFVLYATVDAVNMFTTAWLTFLNCPFIVTLNI (SEQ ID NO: 172)
TM3-(78) YAIFTVDAVNMFTVLYATAWLTFLNCPFIVTLNI (SEQ ID NO: 173)
TM3-(79) YAIFVLYATAWLTVDAVNMFTSFLNCPFIVTLNI (SEQ ID NO: 174)
TM3-(80) YAIFVLYATAWLSFLNTVDAVgMFTPFIVTLNI (SEQ ID NO: 175)
TM3-(81) YAIFVLYASAWLTFLNCPFIVSVDAVNMFTTLNI (SEQ ID NO: 176)
TM3-(82) YAIFVLYATAWLSVDMFTTFLNCPFIVTLNI (SEQ ID NO: 177)
TM3-(83) YAISVDAVNMFTFVLYATAWLSFLNCPFIVTLNI (SEQ ID NO: 178)
TM3-(84) YAIFVLYASLTVFSLLAISAWLTFLNCPFIVTLNI (SEQ ID NO: 179)
TM3-(85) YAIFVLYASAWLTLSVFTLLAISFLNCPFIVTLNI (SEQ ID NO: 180)
TM3-(86) YAIFVLYASAWLTFLSLSVFTLLAINCPFIVTLNI (SEQ ID NO: 181)
TM3-(87) YAIFVLYASAWLTFLNPFSLSVFSLLAIIVTLNI (SEQ ID NO: 182)
TM3-(88) YAIFVLYASAWLSFLNLGGVTASFTASVGPFIVTLNI (SEQ ID NO: 183)
TM3-(89) YAIFVLYASAWLSFLNLGGVTASFTASVGVTLNI (SEQ ID NO: 184)
TM3-(90) YAIFVLLGGVTASFTASVNYASAWLSFLNCPFIVTLNI (SEQ ID NO: 185)
TM3-(91) YAIFVLYAIFFFLLFSAWLSFLNCPFIVTLNI (SEQ ID NO: 186)
TM3-(92) YAIFVLYASAWLSFLNCPFIVTLNIIFFFLLFIVTLNI (SEQ ID NO: 187)
TM3-(93) YAIFVLYASAWIFFFLLFLSFLNCPFIVTLNI (SEQ ID NO: 188)
TM3-(94) YAIFVLYASAWLFFTVLASELSVYTLTVSFLNCPFIVTLNI (SEQ ID NO: 189)
TM3-(95) YAIFVLYASAWLSFLFATLGGEIALCPFIVTLNI (SEQ ID NO: 190)
TM3-96) YAIFVLYAFATLGGEIkLSAWLSFLNCPFIVTLNI (SEQ ID NO: 191)
TM3-(97) YAIFFTVLASELSVYTLTVYASAWLSFLNCPFIVTLNI (SEQ ID NO: 192)
TM3-(98) YAIFFPIAALFAIASAWLSFLNCPFIVTILNI (SEQ ID NO: 193)
TM3-(99) YAIFVLYASAWLSFFPIAALFASIPFIVTLNI (SEQ ID NO: 194)
TM3-(100) YAIFVLYASAWLSFLNCPFFPIAALFASILNI (SEQ ID NO: 195)
TM3-(101) YAIFVLYASAWLSLDVLFSTASIMHLSFLNGGEIALWSLIVTLNI (SEQ ID NO: 196)
TM3-(102) YAIFVLYASLDVLFSTASIMHLIALWSLNCPFIVTLNI (SEQ ID NO: 197)
TM3-(103) YAIFVLYAGGEIALWSLSFLNSLDVLFSTASIMLPFIVTLNI (SEQ ID NO: 198)
TM3-(104) YAIFVLYASAWLSFFDVLFSTASIMLFGYLGNFLLNCPFIVTLNI (SEQ ID NO: 199)
TM3-(105) YAIFVLYASAWLFFFLLFGYLSLDVLFSTASIMHLGNFLLPFIVTLNI(SEQ ID NO: 200)
TM3-(106) YAIFVLYASAWLSFLNTACFYVAITASLSLMHLFITEIALIPFIVTLNI (SEQ ID NO: 201)
TM3-(107) YASLDVLFSTAIMHLSAWLTACFYVAITASLCFITEIALICPFIVTLNI (SEQ ID NO: 202)
TM3-(108) YAIFVLYATACFYVAITASLSFLNCPFIVTLNISLDVLFSTASIMHL(SEQ ID NO:203)
TM3-(109) YAITACFYVAITASLCFITEIALIASAWLSFLNCPFIVTLNI (SEQ ID NO: 204)
TM3-(110) YAIFVLYATACFYSTASILNLIMHLCAISLVAIITEIALISAWLSFLN(SEQ ID NO:205)
TM3-(111) YAIFVLYASAWLSFLNACFYICLFASILNLIMHLGVCFLIPFIVTLNI (SEQ ID NO:206)
TM3-(112) YAIFVLYASAWNASILNLIMHLCFYICLFAGVMLILSFLNCPFIVTLNI(SEQ ID NO:207)
TM3-(113) YAI FPFVQCWS IFSLVLIAVVLYFYIAGVCFLIASAWLS FLNCPFIVTI (SEQ ID NO: 208)
TM3-(114) PFVQCVSITVSIFSLVLIAVYAIFVLYASVDAVNMFTSAWCPFIVTLNI (SEQ ID NO:209)
TM3-(115) YAIFGDWSSVDAVNMFTVLYASAWLSFLNCPFIVTLNI (SEQ ID NO:210)
TM3-(116) YAIFVLYAGDWSSAWLSVDAVNMFTSFLNCPFIVTLNI (SEQ ID NO: 211)
TM3-(117) YAIFVLYASAWLGDWSSFLNSVDAVLGMFTPFIVTLNI (SEQ ID NO:212)
TM3-(118) YAIFVLYASAWLSFLNCPFIVGDWSSVDAVNMFTTLNI (SEQ ID NO: 213)
TM3-(119) YAIFVLYASAWLGYLGSVDMFTSFLNCPFIVTGDWSLNI(SEQ ID NO:214)
TM3-(120) YAISVDAVNMFTFVLYAGYLGSAWLSFLNCPFIVTLNI (SEQ ID NO:215)
TM3-(121) YAIFSLSVFSLLAIVLAYASAWLGYLGSFLNCPFIVTLNI (SEQ ID NO: 216)
TM3-(122) YAIFVLYAGYLGAGNMDSLSVFSLLAISAWLSFLNCPFIVTLNI (SEQ ID NO:217)
TM3-(123) YAIFVLYASAWLSLSVFGNMSLLAISFLNCPFIVTLNI (SEQ ID NO:218)
TM3-(124) YAIFVLYASAWLSFLSLSVFGGSLLAINCPFIVTLNI (SEQ ID NO: 219)
TM3-(125) YAIFVLYASAWLSFLNPFSLSVFGSLLAIIVTLNI(SEQ ID NO:220)
TM3-(126) YAIFVLYATAWLTFLSLANCVTATIPFIVTLNI (SEQ ID NO: 221)
TM3-(127) YAIFVLYATAWLSFLNCTSLASSIVVTATIVTLNI (SEQ ID NO: 222)
TM3-(128) YAIFVLYATAWLSFLNVTLNISLACTTTIV(SEQ ID NO: 223)
TM3-(129) YAIFVLYATAWLTFLNTATILSLANLMFIVTLNI(SEQ ID NO:224)
TM3-(130) YAIFVLYATAWLSFLNMATILNLPFSVDAVIVTLNI (SEQ ID NO:225)
Recently discovered G-proteins also can be used according to the presently claimed invention to provide GPR polypeptides of the present invention, based on the teaching and guidance presented herein. Exampled of such GPR polypeptides of the present invention may include, as non-limiting examples, GPR polypeptides corresponding to transmembrane domain III, e.go, as follows:
TM3-(131) ISTMYTVTGRWTLGQVVCDFWLSSDITCCTASILHLCVIAL (SEQ ID NO: 226)
TM3-(132) ILYGYRWPLPSKLCAVWIYLDVLFSTASIMHLCAISL (SEQ ID NO: 227 )
TM3-(133) IIYIVMDRWKLGYFLCEVWLSVDMTCCTCSILHLCVIAL (SEQ ID NO :228)
TM3-(134) IADKTVRVAMGAENDLGYNFRSDDVCGHCWQWYCSL (SEQ ID NO: 229)
TM3-(135) ILNYWPFGLALCHFVNYSQAVSVLVSAYTLVAISI (SEQ ID NO:230)
TM3-(136) ILGRWEFGIHLCKLWLTCDVLCCTSSILNLCAIALD (SEQ ID NO: 231)
TM3-(137) IMASVMHRHCLPLIGICLSSERHCLVSIFVELGAL (SEQ ID NO:232)
Further non-limiting examples of consensus GPR polypeptides for transmembrane domain III of several or many, such as 1-500, or any range or value therein, more recently discovered G-protein receptors are as follows:
TM3-(138) YAIFVLYASAWLSFLNCPFISILHLCVIALVTLNI (SEQ ID NO:233)
TM3-(139) YAIFVLYATAWLSFLNCPFISILNLCAIALDVTLNI (SEQ ID NO:234)
TM3-(140) YAIFVLYATAWLTFLNCPFISIFVELGALVTLNI (SEQ ID NO: 235 )
TM3-(141) YAIFVLYASAWLTFLNCPFISIFVELSIMHLCAISLGALVTLNI (SEQ ID NO: 236)
TM3-(142) WAIFVLYAILGRWEFGIHLCKLWLTSAWLSIMHLCAISLSFLNCPFIVTLNI (SEQ ID NO:237)
TM3-(143) WAIFVLYAILGRWEFGIHLCKLWLTTAWLSIMHLCAISLSFLNCPFIVTLNI (SEQ ID NO: 238)
TM3-(144) WAIFVLYATAWLTFLNCPFSIMHLCAISLIVTLNI (SEQ ID N0:239)
TM3-(145) WAIFVLYASAWLTFLNCPFISIMHLCAISLVTLNI (SEQ ID NO: 240)
TM3-(146) YAVFVLYASAWLSFLNMSIMHLCAISLPFIVTLNI (SEQ ID NO: 241)
TM3-(147) YAVFVLYATAWLSFLBTMPFSILNLCAIALDIVTLNI(SEQ ID NO:242)
TM3-(148) YAVFVLYATAWLSILNLCAIALDTFLNMPFIVTLNI (SEQ ID NO:243)
TM3-(149) YAVFVLYASILNLCAIALDSAWLTFLNMPFIVTLNI (SEQ ID NO:244)
TM3-(150) YAFVLYASAWLSFLNCVTASIPFCLVSIFVELGALIVTLNI (SEQ ID NO: 245 )
TM3-(151) YAIFVLYASAWLSFLNCLVSIFVELGALIVVTASIVTLNI (SEQ ID NO: 246)
TM3-(152) YAIFVLYASAWLSFLNVTLNCLVSIFVELGALII (SEQ ID NO: 247)
TM3-(153) YAIFVLYASAWLSFLNTASILNLMFICLVSIFVELGALVTLNI (SEQ ID NO: 248)
TM3-(154) YAIFVLYASAWLSFLNMASILNLPFCLVSIFVELGALVTLNI (SEQ ID NO:249)
TM3-(155) YAIFVLYASAWLSFLNILGRWEFGIHLCKLWLTCDVLCCTSSGILLLAPFIVTLNI (SEQ ID NO:250)
TM3-(156) YAIFVLYASAWLSFLNMILGRWEFGIHLCKLWLTCDVLCCTSSGILLLAPFIVTLNI (SEQ ID NO:251)
TM3-(157) YAIFVLYASAWLILGRWEFGIHLCKLWLTCDVLCCTSSFLNSELSVYTLTVCPFIVTLNI (SEQ ID NO: 252 )
TM3-(158) YAIFVLYAILGRWEFGIHLCKLWLTCDVLCCTSSAWLSFLNMSELSVYTLTVPFIVTLNI (SEQ ID NO:253)
TM3-(159) YAIFVLYASAWLASRWPLPLSVYTLTVSFLNCPFIVTLNI (SEQ ID NO: 254 )
TM3-(160 ) YAIFVLYASAWLASELILYYWRWPLPCLHDLVWLCTCSILHLCVIALSVYTLTVPFIVTLNI (SEQ ID NO:255)
TM3-(161) YAIFVLYASAWLSFLASELSVYASELSSTLHDLVWLWLDVFCVIALTTVNMPFIVTLNI (SEQ ID NO:256)
TM3-(162) YAIFVLYASAWLSFLNGGEIALWSLCPFIILYYWRWPLPCLHDLVSILHCVIALVTLNI (SEQ ID NO:257)
TM3-(163) YVWLWLDVFCCTCSILHLCVIALFVLYASAWLSFLNGGEIALWSLIVTLNI (SEQ ID NO: 258)
TM3-(164) YAIFVLYASAWLAIILYYWRWPLPCLHDLGGEIALWSLNCPFIVTLNI(SEQ ID NO:259)
Non-limiting examples of consensus GPR polypeptides for domain V across several or many, such as 1-500, or any range or value therein, G-protein receptors are as follows:
TM5-(1) CDVFVFVDIMLCTASIFNLCAISVG(SEQ ID NO:260)
TM5-(2) YAIFVLYDIPILCTASIFNLCAISVG(SEQ ID NO:261)
TM5-(3) DYAIFVFVDIFiLMTASIFNLMAISVG(SEQ ID NO:262)
TM5-(4) DYAIFVFVDIMLHTTASTIFNLMATITVG (SEQ ID NO: 263)
TM5-(5) CDVAVVYSSDIMLFYVCTASIFSSNLCAISSVG(SEQ ID NO:264)
TM5-(6) FLFCSLGSFYIPIAVILVDIMLCTASIFNLCAISVG(SEQ ID NO:265)
TM5-(7) YAIFVLYDFLFCSLGSFYIPIAVILIMLCTASIFNLCAISVG (SEQ ID NO: 266)
TM5-(8) DYAIFVFVDIMLMTASIFLFCSLGSFYIPIAVILISVG(SEQ ID NO:267)
TM5-(9) DYAIFVFVDIMLHTTASTIFNLMAFLFCSLGSFYIPIAVILTITVG (SEQ iD NO: 268)
TM5-(10) CDVAVVYSSDIMLFYVCTASIFSSNLFLFCSLGSFYCAISSVG(SEQ ID NO:269)
TM5-(11) CDVFVFVDIMLCTASIFNWYILSSIGSFFAPCLILLVYLLCISVG (SEQ ID NO: 270)
TM5-(12) YAIFVLYDIPILCTASIFNLCAIWYILSSIGSFFAPCLILLVYLSVG (SEQ ID NO: 271)
TM5-(13) DYAIFVFVDIWYILSSIGSFFAPCLILLVYLASIFNLMAISVG(SEQ ID NO:272)
TM5-(14) DYAIWYILSSIGSFFAPCLILLVYLIMLHTTASTIFNLMATITVG (SEQ ID NO: 273 )
TM5-(15) CDVAVVYSSDIMLFYVCWYILSSIGSFFAPCLILLVYLSSNLCAISSVG(SEQ ID NO:274)
TM5-(16) CDVFVFVDIMLCTASIFWYVISSSIGSFFAPCLINHLIrYNLCAISVG(SEQ ID NO:275)
TM5-(17) YAIFVLYDIMLCTASIFNLCAIWlNSISSSIGSFFAPCLINHLVYSVG (SEQ ID NO: 276)
TM5-(18) DYAIFVFVWYVISSSIGSFFAPCLINHLVYDIMLMTASIFNLMAISVG (SEQ ID NO:277)
TM5-(19) DYAIFVFVDIMLHTTASTIFWYVISSSIGSFFAPCLINHLVYTVG (SEQ ID NO: 278)
TM5-(20) CDVAVVYSSDIMLFYVCTASIFSWYVISIGSFFAINHLVYNLCAISSVG (SEQ ID NO: 279 )
TM5-(21) CDVFVFVDIMLCTASIFNLCAITYAISSSVISFYIPVAILVTYT(SEQ ID NO:280)
TM5-(22) YAIFVLYDIMLCTATYAISSSVISFYIPVAILVTYTSIFNLCAISVG (SEQ ID NO: 281)
TM5-(23) DYAIFVFIVDIMILMTATYAISSSVISFYIPVAILYTISVG(SEQ ID NO:282)
TM5-(24) TYAISSSVISFYIPVATDYAIFVFVDIMLHTTASTIFNLMATITVG (SEQ ID NO: 283 )
TM5-(25) CDVAVVYSSDIMLFYVCTATYAISSSVISFYIPVAILVTYTSSVG(SEQ ID NO:284)
TM5-(26) CDVFVFVDFVIYSSWSFYLPFGIFfVLVYACTASIFNLCAISVG (SEQ ID NO:285)
TM5-(27) YAIFVLYDFVIYSSWSFYLPFGVTVLVYASIFNLCAISVG (SEQ ID NO :286)
TM5-(28) DYAIFVFVDFVIYSSWSFYLPFGVTVLVYATASIFNLMAISVG(SEQ ID NO:287)
TM5-(29) DYAIFVFVDFVIYSSVIZSFYLPFGVTVLVYAHTTASTIFNLMATITVG (SEQ ID NO: 288)
TM5-(30) CDVAVVYSSDFVIYSSWSFYLPFGVTVYVCTASIFSSNLCAISSVG (SEQ ID NO: 289 )
TM5-(31) CDVFVFVDIMLCTASYTIYSTCGAFYIPSVLLIILYGNLCAISVG (SEQ ID NO: 290)
TM5-(32) YAIFVLYDIMLCTASYTIYSTCGAFYIPSVLLIILYGNLCAI SVG (SEQ ID NO: 291)
TM5-(33) DYAIFVFVDIMLMTASYTIYSTCGAFYIPSVLLIILYGNLMAISVG (SEQ ID NO: 292)
TM5-(34) DYAIFVFVDIMLHTTASYTIYSTCGAFYIPSVLLIILYGMATITVG (SEQ ID NO: 293)
TM5-(35) CDVAVVYSSDIMSYTIYSTCGAFYIPSVLLIILYGIFSSNLCAISSVG (SEQ ID NO: 294)
TMS- (36) CDVFVFFVLIGSFVAVDIMLCTASIFNLCAISVG (SEQ ID NO:295 )
TM5-(37) YAIFVLYFVLIGSFVADIMLCTASIFNLCAISVG (SEQ ID NO: 296)
TM5-(38) DYAIFVFVFVLIGSFVADIMLMTASIFNLMAISVG (SEQ ID NO: 297)
TMS- (39) DYAI FVFVFVLIGSFVADIMLHTTASTIFNLMATITVG (SEQ ID NO: 298)
TM5-(40) CDVAVVYSSFVLIGSFVADIMLFYVCTASIFSSNLCAISSVG (SEQ ID NO: 299)
TM5-(41) CDVFVFVDIMLCFFIPTLIMVITYFNLCAISVG (SEQ ID NO: 300)
TM5-(42) YAIFVLYDIMLCFFIPTLIMVITYFFNLCAISVG (SEQ ID NO: 301)
TM5-(43) DYAIFVFVDIMLMFFIPTLIMVITYFNLMAISVG (SEQ ID NO: 302)
TM5-(44) DYAIFVFVDIMLHTFFIPTLIMVITYFNIIMATITVG (SEQ ID NO: 303)
TM5-(45) CDVAVVYSSDIMLFYVCFFIPTLIMVITYFSSNLCAISSVG (SEQ ID NO: 304)
TM5-(46) CDVVYGLVDGLVTFYLPLLIMCITYYDIMLCTASIFNLCAI SVG (SEQ ID NO: 305)
TM5-(47) YAIVYGLVDGLVTFYLPLLIMCITYYDIMLCTASIFNLCAISVG (SEQ ID NO: 306)
TM5-(48) DYAIVYGLVDGLVTFYLPLLIMCITYYDIMLMTASIFNLMAISVG (SEQ ID NO: 307)
TM5-(49) DYAIVYGLVDGLVTFYLPLLIMCISSDIMLHTTASTIFNLMATITVG (SEQ ID NO: 308)
TM5-(50) CDVVYDGLVTFYLPLLIMCITYYDIMLFYVCTASIFSSNLCAISSVG (SEQ ID NO: 309)
TM5-(51) CDVFVFVDIMLLVIFLGLVIVIPFVLIIVSYASIFNLCAISVG (SEQ ID NO: 310)
TM5-(52) YAIFVLYDIMLLVIFLGLVIVIPFVLIIVSYAIFNLCAISVG (SEQ ID NO: 311)
TM5-(53) DYAIFVFVDIMLMLVIFLGLVIVIPFVLIIVSYAIFNLMAISVG (SEQ ID NO: 312)
TM5-(54) DYAIFVFVDIMLHTLVIFLGLVIVIPFVLIIVSYAIFNLMATITVG (SEQ ID NO: 313)
TM5-(55) CDVAVVYSSDIMLFLVIFLGLVIVIPFVLIIVSYAIFSSNLCAISSVG (SEQ ID NO: 314)
TM5-(56) CDVFVFVDIMLCTALMIYILGGLIIIIPFLLIVMSYVSIFNLCAISVG (SEQ ID NO: 315)
TM5-(57) YAIFVLYDIMLCTALMIYILGGLIIIIPFLLIVMSYVSIFNLCAISVG (SEQ ID NO:316)
TM5-(58) DYAIFVFVDIMLMTASIFNLMIYILGGLIIIIPFLLIVMSYVLMAISVG (SEQ ID NO: 317)
TM5-(59) DYAI FVFVDIMLHTTASTI LMIYI LGGLI II IPFLLIVMSYVITVG (SEQ ID NO: 318)
TM5-(60) CDVAVVYSSDIMLFYVCTAYILGGLIPFLLIVMTYVS I FTNLCAI S SVG ((SEQ ID NO: 319)
TM5-(61) CDVFVFVDIMLCTASIFNLLMIHIMEVIIIVIPFVLIVISYACAISVG (SEQ ID NO: 320)
TM5-(62) YAIFVLYDIMLCTASIFNLLMIHIMEVIIIVIPFVLIVISYACAISVG (SEQ ID NO: 321)
TM5-(63) DYAIFVFVDIMLMTASIFIIHIEVIIIVIPFIIVISYAISVG (SEQ ID NO: 322)
TM5-(64) DYAIFVFVDIMLHTTASTILMIHIMEVIIIVIPFVLIVISYAITVG (SEQ ID NO: 323)
TM5-(65) CDVAVVYSSDIMLFYVCTASIFLMIHIMEVIIIVIPFVLIVISYAAISSVG (SEQ ID NO: 324)
Non-limiting examples of longer consensus GPR polypeptides for domain V across several or many, such as 1-500, or any value or range therein, G-protein receptors are as follows:
TM1-(1)
TM1NWPALSIWIIINTIGGNILVIMAVSIYTSLDVMLCTASILNLLISLFVLIGSFVAFFIPLTIMVITYFLFNVFFVW IGYVCSSSLGINPVIIYTLF (SEQ ID NO: 325)
TM1- (2)
NWPALSIWIIINTIGGNILVIMAVTIYTTLDVMLCTATILNLLISLFVLIGTFVAFFIPLTIMVITYFLFNVFFVWIGY VCTTTLGINPVIIYTLF (SEQ ID NO: 326)
TM1-(3)
NWPALTIWIIIBITIGGNILVIMAVSIYTTLDVMLCTATILNLLITLFVLIGTFVAFFIPLTIMVITYFLFNVFFVWIGY VCSTSLGINPVIIYTLF (SEQ ID NO: 327)
TM1- (5)
NWPALTIWIIINTIGGNILVIMAVTIYTTLDVMLCTATILNLLITLFVLGTFVAFFIPLTIMVITYFLFNVFFVWIGY VCTLGINPVIIYTLF (SEQ ID NO: 328)
TM1-(6)
NWKNWSALLTTVVIILTIAGNILVIMAVSSLDVMLCTASILNLLISLFVLGSFVAFFIPLTIMVITYFLFNVFFVWIGY VCSSSLGINPVIIYTLF (SEQ ID NO: 329)
TM1- (7)
ITITVVLAVLILITVAGNVVVCIAVGSIYTSLDVMLCTASILNLLISLFVLIGSFVAFFIPLTIMVITYFLFNVFFVWIG YVCSSSLGINPVIIYTLF (SEQ ID NO: 330)
TM1-(8)
TLTLVCLACLUSLTVFGNVLVIIAVFSLDVMLCTASILNLLISLFVLIGSFVAFFIPLTIMVITYFLFNVFFVWIGYVCS SSLGINPVIIYTLF (SEQ ID NO:331)
TM1-(9)
TAAIAAAITFLILFTIFGNALVIIAVLSIYTSLDVMLCTASILNLLISLFVLIGSFVAFFIPLTIMVITYFLFNVFFVWI GYVCSSSLGINPVIIYTLF (SEQ ID NO: 332)
TM1-(10)
AISVGLVLGAFILFAIVGNILVILSVANWPALSIVVIIINTIGGNILVIMAVSIYTSLDVLMLCTASILNLLISLFVLIGS FVAFFIPLTIMVITYFLFNVFFVWIGYVCSSSLGINPVIIYTLF (SEQ ID NO: 333)
TM1- (ii)
AALAGALLALAVLATVGGNLLVIVAIASLDVMLCTASILNLLISLFVLIGSFVAFFIPLTIMVITYFLFNVFFVWIGYVC SSSLGINPVIIYTLF(SEQ ID NO: 334)
TM1-(12)
TAGDCLIMLIVLLIVAGNVLVIVAISLDVMLCTASILNLLISLFVLIGSFVAFFIPLTIMVITYFLFNVFFVWIGYVCSS SLGINPVIIYTLF (SEQ ID NO: 335)
TM1-(13)
VITIAVVTAVVSLMTIVGNVLVMISFSIYTSLDVMLCTASILNLLISLFVLIGSFVAFFIILTIMVITYFLFNVFFVWIG YVCSSSLGINPVIIYTLF (SEQ ID NO: 336)
TM1(14)
IATVRGSLSLVTVVGNILVMLSISIYTSLDVMLCTASILNLLISLFVLIGSFVAFFIPLTIMVITYFLFNVFFVWIG YVCSSSLGINPVIIYTLF (SEQ ID NO: 337)
TM1-(15)
WFIAFLTGILALVTIIGNILVIVSFSIYTSLDVMLCTASILNLLISLFVLIGSFVAFFIPLTIMVITYFLFNVFFVWIGY VCSSSLGINPVIIYTLF (SEQ ID NO: 338)
Non-limiting examples of longer consensus GPR polypeptides for domain V across several or many, such as 1-500, or any value or range therein, G-protein receptors are as follows:
TM3-(165)
NWPALSIVVIIINTIGGNILVIMAFFAVWIGYVCSSSLGINPVIIYTLF (SEQ ID NO: 339)
TM3-(166)
NWPALSIWIIINTIGGNILVIMAFFACFVLVLTQSSIFSLLAIAIFVLIGSFVAFFIPLTIMVITYFLFNVFFVWIGYV CSSSLGINPVIIYTLF (SEQ ID NO: 340)
TM3-(167)
NWPALSIWIIINTIGGNILVIMAVMVACPVLILTQSSIIALLAIAVSFVAFFIPLTIMVITYFLFNVFFVWIGYVCSSS LGINPVIIYTLF (SEQ ID NO:341)
TM3-(168)
NWPALSIVVIIINTIGGNILVIMAVLWLALDYVASNASVLNLLLISFFFIPLTIMVITYFLFNVFFVWIGYVCSSSLGIN PVIIYTLF(SEQ ID NO: 342)
TM3-(169)
NWPALSIWIIINTIGGNILVIMAVLYVVSNASVMIGLLIISSFVAFFIPLTIMVITYFLFNVFFVWIGYVCSSSLGINPV IIYTLF (SEQ ID NO: 343)
TM3-(170)
NWPALSIWIIINTIGGNILVIMAVLWIAIDYVASNASVLNLLVISFGSFVAFFiPLTIMVITYFLFNVFFVWIGYVCSS SLGINPVIIYTLF (SEQ ID NO: 344)
TM3-(171)
NWPALSIWIIINTIGGNILVIMAVLFPFLQKSSVGITVLNLCALSGSFVAFFIPLTIMVITYFLFNVFFVWIGYVCSSS LGINPVIIYTLF (SEQ ID NO:345)
TM3-(172)
NWPALSIWIIINTIGGNILVIMAVCITYLQYLGINASSCSITAFTIIGSFVAFFIPLTIMVITYFLFNVFFVWIGYVCS SSLGINPVIIYTLF (SEQ ID NO:346)
TM3-(173)
NWPALSIWIIINTIGGNILVIMAVFHNFFPIAKLFASIYSMTAVAGSFVAFFIPLTIMVITYFLFNVFFVWGIGYVCSSS LGINPVIIYTLF(SEQ ID NO: 347)
TM3-(174)
NWPALSIWIIINTIGGNILVIMAVIASASVSFNLYASVFLLTCLSIGSFVAFFIPLTIMVITYFLFNVFFVWIGYVCSS SLGINPVIIYTLF (SEQ ID NO:348)
As another non-limiting, illustrative example of a GPR polypeptide consensus sequences across each individual or different transmembrane domains of 5-HT receptors may be made, such as for 5-HT, as the following:
5HT consensus(4) KNASALLSVIIINSIGGNVVTAVS (SEQ ID NO:89);
5HT consensus(5) YFLMSLAVTDLWSFVMPVSAL (SEQ ID NO:90);
5HT consensus(6) AITKIAITWAISGVSVPFIPVWG (SEQ ID NO:91); and
5HT consensus(7) LGIIFGTFIIIWLPFFITNLVSPI (SEQ ID NO:92);
Wherein variations and substitutions of amino acids may be made as described herein.
Alternatively, 5-HT consensus sequences may be provided as consensus peptides of the present invention as consensus peptides for individual transmembrane domains, such as 5-HT domains III, V and VII, e.g., as follows:
5-HT consensus (8): IWISLDVLFSTASSIMHLCAISL (SEQ ID NO:93)
3-HT consensus (9): GYTIYSTLVTFYIPSVIMVITYG (SEQ ID NO:94)
5-HT consensus (10): LLNFFNWIGYLNSLINPVIYTLF (SEQ ID NO:95)
This invention is also directed to an antibody which binds an epitope specific for a GPR polypeptide of the present invention and the use of such an antibody to detect the presence of, or measure the quantity or concentration of, the GPR protein in a cell, a cell or tissue extract, a biological fluid, an extract thereof, a solution, or sample, in vitro, in situ, or in vivo.
The term "antibody" is meant to include polyclonal antibodies, monoclonal antibodies (mAbs), chimeric antibodies, anti-idiotypic (anti-Id) antibodies to antibodies specific for GPR polypeptide of the present invention, as well as fragments, consensus polypeptides or chemical derivatives thereof.
Polyclonal antibodies are heterogeneous populations of antibody molecules derived from the sera of animals immunized with an antigen.
A monoclonal antibody contains a substantially homogeneous population of antibodies specific to antigens, which population contains substantially similar epitope binding sites. MAbs may be obtained by methods known to those skilled in the art. See, for example Kohler and Milsrein, Nature 256:495-497 (1975); U.S. Pat. No. 4,376,110; Ausubel et al, eds., Current Protocols in Molecular Biology, Wiley Interscience, N.Y., (1987, 1992); and Harlow and Lane Antibodies: A Laboratory Manual Cold Spring Harbor Laboratory (1988), the contents of which references are incoporated entirely herein by reference. Such antibodies may be of any immunoglobulin class including IgG, IgM, IgE, IgA, GILD and any subclass thereof. A hybridoma producing a mAb of the present invention may be cultivated in vitro, in situ or in vivo. Production of high miters of tabs in vivo or in si tu makes this the presently preferred method of production.
Chimeric antibodies are molecules different portions of which are derived from different animal species, such as those having variable region derived from a murine mAb and a human immunoglobulin constant region, which are primarily used to reduce immunogenicity in application and to increase yields in production, for example, where murine mAbs have higher yields from hybridomas but higher immunogenicity in humans, such that human/murine chimeric mAbs are used. Chimeric antibodies and methods for their production are known in the art (Cabilly et al, Proc. Natl. Acad. Sci. USA 81:3273-3277 (1984); Morrison et al., Proc. Natl. Acad. Sci. USA 81:6851-6855 (1984); Boulianne et al., Nature 312:643-646 (1984); Cabilly et al., European Patent Application 125023 (published Nov. 14, 1984); Neuberger et al. , Nature 314:268-270 (1985); Taniguchi et al., European Patent Application 171496 (published Feb. 19, 1985); Morrison et al., European Patent Application 173494 (published Mar. 5, 1986); Neuberger et al., PCT Application WO 86/01533, (published Mar. 13, 1986); Kudo et al., European Patent Application 184187 (published Jun. 11, 1986); Morrison et al., European Patent Application 173494 (published Mar. 5, 1986); Sahagan et al. , J. Immunol. 137:1066-1074 (1986); Robinson et al., International Patent Publication No. PCT/US86/02269 (published 7 May 1987); Liu et al., Proc. Natl. Acad. Sci. USA 84: 3439-3443 (1987); Sun et al. , Proc. Natl. Acad. Sci. USA 84:214-218 (1987); Better etal., Science 40:1041-1043 (1988); and Harlow and Lane Antibodies: A Laboratory Manual Cold Spring Harbor Laboratory (1988)). These references are incorporated entirely herein by reference.
An anti-idiotypic (anti-Id) antibody is an antibody which recognizes unique determinants generally associated with the antigen-binding site of an antibody. An Id antibody carl be prepared by immunizing an animal of the same species and genetic type (e.g., mouse strain) as the source of the mAb with the mAb to which an anti-Id is being prepared. The immunized animal will recognize and respond to the idiotypic determinants of the immunizing antibody by producing an antibody to these idiotypic determinants (the anti-Id antibody). See, for example, U.S. Pat. No. 4,699,880, which is herein entirely incorporated by reference.
The anti-Id antibody may also be used as an "immunogen" to induce an immune response in yet another animal, producing a so-called anti-anti-Id antibody. The anti-anti-Id may be epitopically identical to the original mAb which induced the anti-Id. Thus, by using antibodies to the idiotypic determinants of a mAb, it is possible to identify other clones expressing antibodies of identical specificity.
Accordingly, mAbs generated against a GPR polypeptide of the present invention may be used to induce anti-Id antibodies in suitable animals, such as BALB/c mice. Spleen cells from such immunized mice are used to produce anti-Id hybridomas secreting anti-Id mAbs. Further, the anti-Id mAbs can be coupled to a immunogenic carrier such as keyhole limpet hemocyanin (KLH) or cationized bovine serum albumin and used to immunize additional BALB/c mice. Sera from these mice will contain anti-anti-Id antibodies that have the binding properties of the original mAb specific for a GPR polypeptide epitope.
The anti-IdmAbs thus have their own idiotypic epitopes, or "idiotopes" structurally similar to the epitope being evaluated.
The term "antibody" is also meant to include both intact molecules as well as fragments thereof, such as, fcr example, Fab and F(ab').sub.2, which are capable of binding antigen. Fab and F(ab').sub.2 fragments lack the Fc fragment of intact antibody, clear more rapidly from the circulation, and may have less non-specific tissue binding than an intact antibody (Wahl et al., J. Nucl. Med. 24:316-325 (1983)).
It will be appreciated that Fab and F(ab').sub.2 and other fragments of the antibodies useful in the present invention may be used for the detection and quantitation of a GPR polypeptide according to the methods disclosed herein for intact antibody molecules. Such fragments are typically produced by proteolytic cleavage, using enzymes such as papain (to produce Fab fragments) or pepsin (to produce F(ab').sub.2 fragments).
An antibody is said to be "capable of binding" a molecule if it is capable of specifically reacting with the molecule to thereby bind the molecule to the antibody. The term "epitope" is meant to refer to that portion of any molecule capable of being bound by an antibody which can also be recognized by that antibody. Epitopes or "antigenic determinants" usually consist of chemically active surface groupings of molecules such as amino acids. lipids or sugar side chains and have specific three dimentional structural characteristics as well as specific charge characteristics.
An "antigen" is a molecule or a portion of a molecule capable of being bound by an antibody which is additionally capable of inducing an animal to produce antibody capable of binding to an epitope of that antigen. Am antigen may have one, or more than one epitope. The specific reaction referred to above is meant to indicate that the antigen will react, in a highly selective manner, with its corresponding antibody and not with the multitude of other antibodies which may be evoked by other antigens.
The antibodies, or fragments of antibodies, useful in the present invention may be used to quantitatively or qualitatively detect a GPR polypeptide in a sample or to detect presence of cells which express a GPR polypeptide of the present invention. This can be accomplished by immunofluorescence techniques employing a fluorescently labeled antibody (see below) coupled with light microscopic, flow cytometric, or fluorometric detection.
The antibodies (of fragments thereof) useful in the present invention may be employed histologically, as in immunofluorescence or imnunoelectron microscopy, for in si tu detection of a GPR polypeptide of the present invention. In situ detection may be accomplished by removing a histological specimen from a patient, and providing the a labeled antibody of the present invention to such a specimen. The antibody (or fragment. ) is preferably provided by applying or by overlaying the labeled antibody (or fragment) to a biological sample. Through the use of such a orocedure, it is possible no determine not only the presence of a GPR polypeptide but also its distribution on the examined t. issue. Using the present invention, those of ordinary skill will readily perceive that any of wide variety of histological methods (such as staining procedures) can be modified in order to achieve such in situ detection.
Such assays for a GPR polypepnide of the present invention typically comprise incubating a biological sample, such as a biological fluid, a tissue extract, freshly harvested cells such as lymphocytes or leukocytes, or cells which have been incubated in tissue culture, in the presence of a detectably labeled antibody capable of identifying a GPR polypeptide, and detecting the antibody by any of a number of techniques well-known in the art. See, e.g., Harlow and Lane, supra; Ausubel et al, sunera; and Sambrook et al,
The biological sample may be treated with a solid phase support or carrier, such as nitrocellulose, or other solid support or carrier which is capable of immobilizing cells, cell particles or soluble proteins. The support or carrier may then be washed with suitable buffers, followed by treatment with a detectably labeled GPR polypeptide-specific antibody. The solid phase support or carrier may then be washed with the buffer a second time to remove unbound antibody. The amount of bound label on said solid support or carrier may then be detected by known method steps, see, e.g., Harlow, supra; Ausubel, supra; or Sambrook, supra.
By "solid phase support", "solid phase carrier", "solid support", "solid carrier", "support" or "carrier" is intended any support or carrier capable of binding antigen or antibodies. Well-known supports or carriers, include glass, polystyrene, polypropylene, polyethylene, dextran, nylon amylases, natural and modified celluloses, polyacrylamides, gabbros, and magnetite. The nature of the carrier can be either soluble to some extent or insoluble for the purposes of the present invention. The support material may have virtually any possible structural configuration so long as the coupled molecule is capable of binding to an antigen or antibody. Thus, the support or carrrier configuration may be spherical, as in a bead, or cylindrical, as in the inside surface of a test tube, or the external surface of a rod. Alternatively, the surface may be flat such as a sheet, polymer test strip, etc. Preferred supports or carriers include polystyrene beads. Those skilled in the art will know many other suitable carriers for binding antibody or antigen, or will be able to ascertain the same by use of routine experimentation.
The binding activity of a given lot of anti-GPR polypeptide antibody may be determined according to well known method steps. Those skilled in the art will be able to determine operative and optimal assay conditions for each determination by employing routine experimentation. See, e.g., Harlow, supra.
Other such steps as washing, stirring, shaking, filtering and the like may be added to the assays as is customary or necessary for the particular situation.
One of the ways in which a GPR polypeptide-specific antibody, anti-idiotype antibody or fragment thereof, can be detectably labeled is by linking the same to an enzyme and use in an enzyme immunoassay (EIA). This enzyme, in turn, when later exposed to an appropriate substrate, will react with the substrate in such a manner as to produce a chemical moiety which can be detected, for example, by spectrophotometric, fluorometric or by visual means. Enzymes which can be used detectably label. the antibody include, but are not limited to, malate dehydrogenase, staphylococcal nuclease, delta-5-steroid isomerase, yeast alcohol dehydrogenase, alpha-glycerophosphate dehydrogenase, triose phosphate isomerase, horseradish peroxidase, alkaline phosphatase, asparaginase, glucose oxidase, beta-galactosidase, ribonuclease, urease, catalase, glucose-6-phosphate dehydrogenase, glucoamylase and acetylcholinesterase. The detection can be accomplished by colorimetric methods which employ a chromogenic substrate for the enzyme. Detection may also be accomplished by visual comparison of the extent of enzymatic reaction of a substrate in comparison with similarly prepared standards. See, Harlow, supra, Ausubel, supra.
Detection may be accomplished using any of a variety of other immunoassays. For example, by radioactivity labeling the antibodies or antibody fragments, it is possible to detect R-PTPase through the use of a radioimmunoassay (RIA). A good description of RIA maybe found in Laboratory Techniques and Biochemistry in Molecular Biology, by Work et al., North Holland Publishing Company, N.Y. (1978) with particular reference to the chapter entitled "An Introduction to Radioimmune Assay and Related Techniques" by Chard, incorporated entirely by reference herein. The radioactive isotope can be detected by such means as the use of a .gamma.-counter, a scintillation counter or by autoradiography.
It is also possible to label an anti-GPR polypeptide antibody, anti-idiotype antibody or fragment thereof, with a fluorescent compound. When the fluorescently labeled antibody is exposed to light of the proper wave length, its presence can be then be detected due to fluorescence. Among the most commonly used luorescent labelling compounds are fluorescein isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, o-phthaldehyde and fluorescamine, commercially available, e.g., from Molecular Probes, Inc. (Eugene, Oreg.).
The antibody can also be detectably labeled using fluorescence emitting metals such as .sup.152 EU, or others of the lanthanide series. These metals can be attached to the antibody using such metal chelating groups as diethylenetriamine pentaacetic acid (EDTA).
The antibody also carl be detectably labeled by coupling it to a chemiluminescent compound. The presence of the chemiluminescent-tagged antibody is then determined by detecting the presence of luminescence that arises during the course of a chemical reaction. Examples of particularly useful chemiluminescent labeling compounds are luminol, isoluminol, theromatic acridinium ester, imidazole, acridinium salt and oxalate ester.
Likewise, a hieluminescent compound may be used to label the antibody of the present invention. Bioluminescence is a type of chemiluminescence found in biological systems in which a catalytic protein increases the efficiency of the chemiluminescent reaction. The presence off a bioluminescent protein is determined by detecting the presence of luminescence. Important bioluminescent compounds for purposes of labeling are luciferin, luciferase and aequorin.
An antibody molecule of the present invention may be adapted for utilization in a immunometric assay, also known as a "two-site" or "sandwich" assay. In a typical immunometric assay, a quantity of unlabeled antibody (or fragment of antibody) is bound to a solid support or carrier and a quantity of detectably labeled soluble antibody is added to permit detection and/or quantitation of the ternary complex formed between solid-phase antibody, antigert, and labeled antibody.
Typical, and preferred, immunometric assays include "forward" assays in which the antibody bound to the solid phase is first contacted with the sample being tested to extract the antigert form the sample by formation of a binary solid phase: antibody-antigen omplex. After a suitable incubation period, the solid support or carrier is washed to remove the residue of the fluid sample, including unreacted arttigon, if any, and then contacted with the solution containing an unknown quantity of labeled antibody (which functions as a "reporter molecule"). After a second incubation period to permit the labeled antibody to complex with the antigert bound to the solid support or carrier through the unlabeled antibody, the solid support or carrier is washed a second time to remove the unreacted labeled antibody.
In another type of "sandwich" assay, which may also be useful with the antigens of the present inventicn, the so-called "simultaneous" and "reverse" assays are used. A "simultaneous" and "reverse" assays are used. A simultaneous assay involves a single incubation step as the antibody bound to the solid support or carrier and labeled antibody are both added to the sample being tested at the same time. After the incubation is completed, the solid support or carrier is washed to remove the residue of fluid sample and uncomplexed labeled antibody. The presence of labeled antibody associated with the solid support or carrier is then determined as it would be in a conventional "forward" sandwich assay.
In the "reverse" assay, stepwise addition first of a solution of labeled antibody to the fluid sample followed by the addition of unlabeled antibody bound to a solid support or carrier after a suitable incubation period is utilized. After a second incubation, the solid phase is washed in conventional fashion to free it of the residue of the sample being tested and the solution of unreated labeled antibody. The determination of labeled antibody associated with a solid support or carrier is then determined as in the "simultaneous" and "forward" assays. See, e.g., for the above-mentioned immunological techniques, Harlow, supra; Ausubel et al, supa; and Sambrook et al, supra. GPR polypeptides of the present invention can be made by chemical synthesis or by recombinant methods, wherein chemical synthesis is preferred.
Synthetic production of transmembrane proteins of the present invention
GPR polypeptides, variants and chemical derivatives thereof can be synthesized according to known method steps, including portions of known GPR transmembrane domains, consensus peptides thereof, conservative substitution derivative thereof or functional derivatives thereof.
Chemical polypeptide synthesis is a rapidly evolving area in the art, and methods of solid phase polypeptide synthesis are well-described in the following references, hereby entirely incorporated by reference: (Merrifield, B., J. Amer. Chem. Soc. 5:2149-2154 (1963); Merrifield, B., Science 232:341-347 (1986); Wade, J. D. et al., Biopolymers 25:S21-S-37 (1986); Fields, G. B., Int. J. Polypeptide Prot. Res. 35:161 (1990); MilliGen Report Nos. 2 and 2a, Millipore Corporation, Bedford, Mass., 1987) Ausubel et al, supra, and Sambrook et al, supra.
In general, as is known in the art, such methods involve blocking or protecting reactive functional groues, such as free amino, carboxyl and thio groups. After poiypeptide bond formation, the protective groups are removed ior de-protected). Thus, the addition of each amino acid residue requires several reaction steps lot protecting and deprotecting. Current methods utilize solid phase synthesis, wherein the C-terminal amino acid is covalently linked to an insoluble resin particle large enough to be separated from the fluid phase by filtration. Thus, reactants are removed by washing the resin particles with appropriate solvents using an automated programmed machine. The completed polypeptide chain is cleaved from the resin by a reaction which does not affect polypeptide bonds.
In the more classical method, known as the "tBoc method," the amino group of the amino acid being added to the resin-bound C-terminal amino acid is blocked with tert-butyloxycarbonyl chloride (tBoc). This protected amino acid is reacted with the bound amino acid in the presence of the condensing agent dicyclohexylcarbodiimide, allowing its carboxyl group to form a polypeptide bond the free amino group of the bound amino acid. The amino-blocking group is then removed by acidification with trifluoroacetic acid (TFA); it subsequently decomposes into gaseous carbon dioxide and isobutylene. These steps are repeated cyclically for each additional amino acid residue. A more vigorous treatment with hydrogen fluoride (HF) or trifluoromethanesulfonyl derivatives is common at the end of the synthesis to cleave the benzyl-derived side chain protecting groups and the polypeptide-resin bond.
More recently, the preferred "Fmoc" technique has been introduced as an alternative synthetic approach, offering milder reaction conditions, simpler activation procedures and compatibility with continuous flow techniques. This method was used, e.g., to prepare the peptide sequences disclosed in the present application. Here, the .varies.-amino group is protected by the base labile 9-fluorenylmethoxycarbonyl (Fmoc) group. The benzyl side chain protecting groups are replaced by the more acid labile t-butyl derivatives. Repetitive acid treatments are replaced by deprotection with mild base solutions, e.g., 20% piperidine in dimethylformamide (DMF), and the final HF cleavage treatment is eliminated. A TFA solution is used instead to cleave side chain protecting groups and the polypeptide resin linkage simultaneously.
At least three different polypeptide-resin linkage agents can be used: substituted benzyl alcohol derivatives that can be cleaved with 95% TFA to produce a polypeptide acid, methanolic ammonia to produce a polypeptide amide, or 1% TFA to produce a protected polypeptide which can then be used in fragment condensation procedures, as described by Atherton, E. etal., J. Chem. Sec. Perkin Trans. 1:538-546 (1981) and Sheppard, R. C. et al., Int. J. Polypeptide Prot. Res. 20:451-454 (1982). Furthermore, highly reactive Fmoc amine acids are available as pentafluorophenyl esters or dihydro-oxobenzotriazine esters derivatives, saving the step of activation used in the tBoc method.
Sequences available to use as a basis for polypeptide synthesis can be based on published sequences of G-protein coupled receptors, ligands and/or effectors, wherein the transmembrane or functional domains correspond to sections of hydrophobic or other amine acids of 5 to 100 amine acids, such as 5-10, 10-15, 15-25, 20-25, 23-27, 25-30, 28-35, 20-40, 10-40, 20-30, 30-40, 40-50, 10-80, 20-60 or 25-40 amine acids in length. Recombinant production of GPR polypeptides can be accomplished according to known method steps. Standard reference works setting forth the general principles of recombinant DNA technology include Watson, J. D. et al., Molecular Biology of the Gone, Volumes I and II, The Benjamin/Cummings Publishing Company, Inc., publisher, Menlo Park, Calif. (1987); Darnell, J. E. et al., Molecular Cell Biology, Scientific American Books, Inc., publisher, New York, N.Y. (1986); Lewin, B. M., Genes III, John Wiley & Sons, publishers, New York, N.Y. (1989); Old, R. W., et al., Principles of Gene Manipulation: An Introduction to Genetic Engineering, 2d edition, University of California Press, publisher, Berkeley, Calif. (1981); Ausubel et al, eds. , Current Protocols in Molecular Biology, Wiley Interscience, publisher, New York, N.Y. (1987, 1992); and Sambrook et al., Molecular Cloning: A Laboratory Manual, Second Edition, Cold Spring Harbor Laboratory, publisher, Cold Spring Harbor, N.Y. (1989), the entire contents of which references are herein incorporated by reference.
A nucleic acid sequence ellcoding a GPR polypeptide of the present invention may be recombined with vector DNA in accordance with conventional techniques, including blunt-ended or staggered-ended termini for ligation, restriction enzyme digestion to provide appropriate termini, filling in of cohesive ends as appropriate, alkaline phosphatase treatment to avoid undesirable joining, and ligation with appropriate ligases. Techniques for such manipulations are disclosed, e.g., by Ausubel et al, supra, and are well known in the art.
A nucleic acid molecule, such as DNA is said to be capable of expressing" a polypepzide if it contains nucleotide sequences which contain transcriptional and translational regulatory information and such sequences are "operably linked" to nucleotide sequences which encode the polypeptide. An operable linkage is a linkage in which the regulatory DNA sequences and the DNA sequence sought to be expressed are connected in such a way as to permit gene expression as GPR polypeptides in recoverable amounts. The precise nature of the regulatory regions needed for gene expression may vary from organism to organism, as is well known in the analogous art. See, e.g., Sambrook, supra and Ausubel supra.
The present invention accordingly encompasses the expression of a GPR polypeptide, in either prokaryotic or eukaryotic cells, although eukaryotic expression is preferred.
Preferred hosts are bacterial or eukaryotic hosts including bacteria, yeast, insects, fungi, bird and mammalian cells either in vivo, or in situ, or host cells of mammalian, insect, bird or yeast origin. It is preferred that the mammalian cell or tissue is of human, primate, hamster, rabbit, rodent, cow, pig, sheep, horse, goat, dog or cat origin, but any other mammalian cell may be used.
Further, by use of, for example, the yeast ubiquitin hydrolase system, in vivo synthesis of ubiquitin-transmembrane polypeptide fusion proteins may be accomplished. The fusion proteins so produced may be processed in vivo or purified and processed in vitro, allowing synthesis of a GPR polypeptide of the present invention with a specified amino terminus sequence. Moreover, problems associated with retention of initiation codon-derived methionine residues in direct yeast (or bacterial) expression may be avoided. Sabin etal., Bio/Technol. 7(7): 705-709 (1989); Miller et al., Bio/Technol. 7(7): 698-704 (1989).
Any of a series of yeast gene eggression systems incorporating promoter and termination elements from the actively expressed genes coding for glycolytic enzymes produced in large quantities when yeast are grown in mediums rich in glucose can be utilized to obtain GPR polypeptides of the present invention. Known glycolytic genes can also provide very efficient transcriptional control signals. for example, the promoter and terminator signals of the phosphoglycerate kinase gene can be utilized.
Production of GPR polypeptides or functional derivatives thereof in insects can be achieved, for example, by infecting the insect host with a baculovirus engineered to express transmembrane polypeptide by methods known to those of skill. See Ausubel etal, eds. Current Protocols in Molecular Biology, Wiley Interscience, .sctn..sctn.16.8-16.11 (1987, 1992).
In a preferred embodiment, the introduced nucleotide sequence will be incorporated into a plasmid or vital vector capable of autonomous replication in the recipient host. Any of a wide variety of vectors may be employed for this purpose. See, e.g., Ausubel et al, supra, .sctn..sctn.1.5, 1.10, 7.1, 7.3, 8.1, 9.6, 9.7, 13.4, 16.2, 16.6, and 16.8-16.11. Pactors of importance in selecting a particular plasmid or vital vector include: the ease with which recipient cells that contain the vector may be recognized and selected from those recipient cells which do not contain the vector; the number of copies of the vector which are desired in a particular host; and whether it is desirable to be able to "shuttle" the vector between host cells of different species.
[Preferred prokaryotic vectors known in the art include plasmids such as those capable of replication in E. coli (such as, for example, pBR322, ColE1, pSC101, pACYC 184, .pi.VX). Such plasmids are, for example, disclosed by Maniatis, T., et al. (Molecular Cloning, A Laboratory Manual, Second Edition, Cold Spring Harbor Press, Cold Spring Harbor, N.Y. (1989); Ausubel et al, eds., Current Protocols in Molecular Biology, Wiley Interscience, New York, N.Y. (1987, 1992)). Bacillus plasmids include pC194, pC221, pT127, etc. Such plasmids are disclosed by Gryczan, T. (In: The Molecular Biology of the Bacilli, Academic Press, N.Y. (1982), pp. 307-329). Suitable Streptomyces plasmids include pIJ101 (Kendall, K. J., et al., J. Bacteriol. 169:4177-4183 (1987)) , and streptomyces bacteriophages such as .phi.C31 (Chater, K. F. , et al. , In: Sixth International Symposium on Actinomycetales Biology, Akademiai Kaido, Budapest, Hungary (1986), pp. 45-54). Pseudomonas plasmids are reviewed by John, J. F., et al. (Rev. Infect. Dis. 8:693-704 (1986)), and Izaki, K. (Jpn. J. Bacteriol. 33:729-742 (1978); and Ausubel et al, supra).
The expressed protein may be isolated and purified in accordance with conventional conditions, such as extraction, precipitamion, chromatography, affinity chromatography, electrophoresis, or the like. Por example, the cells may be collected by centrifugation, or with suitable buffers, lysed, and the protein isolated by column chromatography, for example, on DEAE-cellulose, phosphocellulose, polyribocytidylic acid-agarose, hydroxyapatite or by electrophoresis or immunoprecipitation. Alternatively, thetransmembrane polypeptide or functional derivative thereof may be isolated by the use of anti-transmembrane polypeptide antibodies. Such antibodies may be obtained by well-known methods, some of which are mentioned below. These antibodies may be immobilized on cellulose, agarose, hollow fibers, or cellulose filters by covalent chemical derivatives by methods well known to those skilled in the art.
As discussed herein, GPR poiypeptides of the present invention may be further modified for purposes of drug design, such is for example to reduce immunogenicity, to prevent solubility and/or enhance delivery, or to prevent clearance or degradation.
Appropriate modification of the primary amino acid sequence of GPR polypeptides of the present invention, obtained by mutagenesis or utilizing fragments of other related forms of G-protein transmembrane proteins, as described herein, will allow the creation of molecules which bind G-protein coupled receptors with higher affinity than that exhibited by naturally occurring transmembrane domains. Small polypeptides that are provided according to the present invention which polypeptides maintain G-protein coupled receptor binding inhibition activity, are expected to have two advantages over larger polypeptides. These advantages include (1) greater stability and diffusibility, and (2) less immunogenicity.
Since polypeptides according to the present invention are generally small (10-40, 20-30, 15-25, 30-45 amino acids), cell or tissue sources of G-protein coupled receptors are not required to practice the present invention, since known polypeptide syntheses steps can be used without undue experimentation to provide GPR polypeptides or sequences substantially corresponding thereto.
Pharmaceutical Preparations
Preparations of GPR polypeptides for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions, which may contain auxiliary agents or excipients which are known in the art. Pharmaceutical compositions such as tablets and capsules can also be prepared according to routine methods.
By the term "protection" from infection or disease as used herein is intended "prevention," "suppression" or "treatment." "Prevention" involves administration of a GPR polypeptide, polypeptide derivative, or anti-idiotypic antibody prior to the induction of the disease.
"Suppression" involves administration of the composition prior to the clinical appearance of the disease.
"Treatment" involves administration of the protective composition after the appearance of the disease. It will be understood that in human and veterinary medicine, it is not always possible to distinguish between "preventing" and "suppressing" since the ultimate inductive event or events may be unknown, latent, or the patient is not ascertained until well after the occurrence of the event or events. Therefore, it is common to use the term "prophylaxis" as distinct from "treatment" to encompass both "preventing" and "suppressing" as defined herein. The term "protection," as used herein, is meant to include "prophylaxis."
At least one GPR polypeptide, antibody or anti-idiotypic antibody of the present invention may be administered by any means that achieve their intended purpose, for example, to treat GPR related pathologies, such as psychotic disorders, including schizophrenia, by inhibition of binding of Dopamine D.sub.2 receptors using a GPR polypeptide corresponding to a fragment or consensus portion of a dopamine D.sub.2 transmentrane domain; in the form of a pharmaceutical composition.
For example, administration of such a composition may be by various parenteral routes such as subcutaneous, intravenous, intradermal, intramuscular, intraperitoneal, intranasal, transdermal, or buccal routes. Alternatively, or concurrently, ndministration may be by the oral route. Parenteral administration can be by bolus injection or by gradual perfusion over time.
A preferred mode of using a GPR pharmaceutical composition of the present invention is by intravenous or parenteral application.
A typical regimen for preventing, suppressing, or treating G-protein coupled receptor pathologies, such as dopamine receptor related schizophrenia, comprises administration of an effective amount of a GPR polypeptide, consensus sequence, or chemical derivative thereof, administered over a period of one or several days, up to and including between one week and about 24 months.
It is understood that the dosage of a GPR polypeptide of the present invention administered in vivo or in vitro will be dependent upon the age, sex, health, and weight of the recipient, kind of concurrent treatment, if any, frequency of treatment, and the nature of the effect desired. The ranges of effective doses provided below are not intended to limit the inventors and represent preferred dose ranges. However, the most preferred dosage will be tailored to the individual subject, as is understood and determinable by one of skill in the art, without undue experimentation.
The total dose required for each treatment may be administered by multiple doses or in a single dose. a GPR polypeptide or functional a chemical derivative thereof may be administered alone or in conjunction with other therapeutics directed to GPR related pathologies, such as a the dopamine receptor related pathology as a non limiting example, or directed to other symptoms of the disease.
Effective amounts of the a GPR polypeptide or composition, which may also include a functional derivative thereof, or a GPR anti-idiotypic antibody, are from about 0.01 .mu.g to about 100 mg/kg body weight, and preferably from about 10 .mu.g to about 50 mg/kg body weight, such 0.05, 0.07, 0.09, 0.1, 0.5, 0.7, 0.9, 1, 2, 5, 10, 20, 25, 30, 40, 45, or 50 mg/kg.
Preparations for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions, which may contain auxiliary agents or excipients which are known in the art. Pharmaceutical compositions such as tablets and capsules can also be prepared according to routine methods.
Pharmaceutical compositions comprising at least one GPR polypeptide of the present invention may include all compositions wherein the GPR polypeptide is contained in an amount effective to achieve its intended purposa. In addition to the GPR polypeptide, a pharmaceutical composition may contain suitable pharmaceutically acceptable carriers, such as comprising excipients and auxiliaries which facilitate processing of the active compounds into preparations which can be used pharmaceutically.
Pharmaceutical compositions include suitable solutions for administration intravenously, subcutaneously, dermally, orally, mucosally, rectally or may by injection or orally, and contain from about 0.01 to 99 percent, preferably from about 20 to 75 percent of active component (i.e. the antibody) together with the excipient. Pharmaceutical compositions for oral administration include tablets and capsules. Compositions which can be administered rectally include suppositories.
EXAMPLE 1
Synthesis of a G-Protein Transmembrane Polypeptide and Consensus Polypeptide
The polypeptides in FIGS. 1-5 were synthesized using the following procedure and include the following characteristics.
Peptide I (SEQ ID NO:I), as shown in FIG. 1, was used as a control for hydrophobic interaction alone as the mechanism of binding and was run in parallel with the test polypeptides described below. Polypeptide II (SEQ ID NO: 2 ) , as shown in FIG. 2, represents a membrane- spanning fragment of transmembrane segment III in the dopamine D.sub.2 receptor. This particular fragment was chosen since it has been implicated in the .beta.-adrenergic receptor as having many res idues which are involved in ligand binding interaction. Polypeptide III (SEQ ID NO:3), as shown in FIG. 3, represents the consensus polypeptide which was developed as a model for the dopamine D.sub.2 system and polypeptide IV (SEQ ID NO:4), as shown in FIG. 4, is a control for length dependence to show how critical the polypeptide length is in binding studies. Polypeptide V (SEQ ID NO:5), as shown in FIG. 5, is a consensus sequence of transmembrane domains of dopamine receptors D.sub.1 and D.sub.2.
The above polypeptides I-V (SEQ ID NOS:1-5), as shown in FIGS. 1-5, respectively, were synthesized using solid phase synthesis on a Milligen 9600 polypeptide synthesizer using Fmoc amino acids (provided by Milligen/Biosearch) and PAL polystyrene resin (Milligen/Biosearch) . Coupling times were 1 hour and the polypeptides were cleaved by trifluoroacetic acid/phenol/thioanisole/ethanedithiol (82.5:5:5:5:2.5) at room temperature for 2 hours. The filtrate was collected and washed with 2 mL of trifluoroacetic acid (TFA) and 1 mL of dichloromethane (DCM). The filtrate was reduced in vacuo to 2 ml in volume and the resulting polypeptide was precipitated out by the addit ion of water. The polypeptides were then dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol [(HFIP) Eastman]; lyophilized; and stored at -20.degree. C. until purification. Polypeptides I-V (SEQ ID NOS:1-5), were purified using reverse-phase HPLC using a preparative Vydac C4 column (Vydac) at 60.degree. C. at a flow rate of 6.0 mL/min with a linear gradient of 0-100% B in a 60 min period at a UV detection wavelength of 275 mm.
Due to the highly hydrophobic nature of these polypeptides, methanol was used with 0.1% (W/V) TFA and 0.5% (W/V) HFIP as solvent A and 2-propanol with 0.1% TPA as solvent B, in order to purify these polypeptides. Further purification was performed with an analytical C4 column (Vydac) with an isocratic qradient of 40% B at a flow rate of 1 ml/min. Identity of the polypeptides was confirmed by Fast-atom bombardment mass spectrometry and electrospray mass spectrometry and amino acid analysis. Stock solutions of polypeptides were made in HFIP and stored at -20.degree. -80.degree. C.
Circular Dichroism (CD). Spectra were recorded on an Aviv model 60 DS circular dichroism spectrophotometer at room temperature with a 1 cm by 1 mm cell. The amplitude of the CD signal was calibrated using 10.1% (w/v) solution of d (+)-camphorsulfonic acid (Aldrich) and the wavelength of the CD signal was set using standard absorbance peaks of benzene vapor. Polypeptide ccncentrations were determined in a Cary 210 UV spectrophotomer wwith the absorbance measured at 280 nm. Helical content was estimated using CD signal intensity according to the method of Chen. et al Biochem. 13:3350-13359 (1974). This calculation compares the experimental ellipticity at. 222 nm ( [.theta.]222) ( [.theta.]) to a theoretical [.theta.]222. The theoretical [.theta.]222 is empirically adjusted to account for differences in polypeptide length and is based on experimental CD data from a series of proteins with known crystal structures. Since both the curve shape and magnitude are important in analysis of a CD spectrum for secondary structure contributions, we also considered qualitatively the contributions to the spectral shapes from different secondary structures using reference curves for poly (L-lysine).
FIG. 6 shows a CD spectrum of the consensus polypeptide III (SEQ ID NO: 3 ) demonstrating that the polypeptide III is only partially helical in a solvent system in which most membrane polypeptides are strongly helical.
Preparation of Small Unilamellar Visicles. Polypeptides were incorporated into DMPC vesicles at lipid:peptide ratio of 147:1 in the followinq manner: polypept ide in HFIP was mixed with dimyrystyroyl-phosphatidylcholine (synthetic) (DMPC) in dry chloroform and dried to a film with a stream of dry nitrogen at 0.degree. C. This residue was then dried further overnight under a vacuum (1.times.10.sup.-2 torr). The residue was then hydrated in 100 mL NaCl and sonicated for a 30-min period under nitrogen at 0.degree. C. The suspension was sedimented for a 30-min at 100,000 q (4.degree. C.) to remove any residual titanium particles and large unilamellar vesicles The supernatant was removed and sedimented once more at 159,000 g for a 45 min period at 4.degree. C. The supernatant in the lower portion was used immediately. This basic procedure has been shown to reliably produce small unilamellar vesicles.
Radioligand Bining Assays. A 0.50 mL volume of 1.00 nM [.sup.3 H]-spiperone (New England specific activity 21.4 Ci/mol) was added to assay tubes which contained 0.5 mL lipid/peptide supernatant, 0.5 mL Tris buffer pH 7.4 and 0.5 mL of cold drug for a final volume of 2.0 mL. Nonspecific binding was defined in the presence of 1 uM of (+) butaclamol or 1 uM spiperone. Appropriate controls for lipid vesicles containing no polypeptide were also run. Assay tubes were prepared in triplicate and the mixture was incubated for 1 h at 25.degree. C. Incubation was terminated by filtration through filters presoaked in 0.1% polyethyleneimine (w/v, Siqma) for at least 1 h prior to use.
Filters were then washed with 6.0 mL of cold 50 mM Tris-HCl buffer, pH 7.40. For detection of radioactivity, filters were placed in 2.0 mL of scintillation fluid (Scintiverse) and incubated for 24 h. The activity of the tritium was determined in a Beckman LS 7500 liquid scintillation counter. Specific binding of [.sup.3 H]-spiperone was defined as the difference in binding in the presence and absence of unlabeled (+) butaclamol.
FIG. 7 shows results of radioligand binding assays comparing polypeptide I (SEQ ID NO:1) as a control unit polypeptide iII (SEQ ID NO:3) according to the present invention. Polypeptide III (SEQ ID NO:3) is shown to unexpectedly provide receptor-like functional binding, as demonstrated by binding to the neuroleptic agent, spiperone, into a stereoselective, concentration-dependent manner.
It has also been demonstrated that as little as 0.1% of a GPR polypeptide according to the present invention is able to form a receptor-like functional binding site. Thus, a GPR polypeptide of the present invention is unexpectedly shown to act both as GPR ligands and GPR binding sites.
All references cited herein, including journal articles or abstracts, published or corresponding U.S. or foreign patent applications, issued U.S. or foreign patents, or any other references, are entirely incorporated by reference herein, including all data, tables, figures, and text presented in the cited references. Additionally, the contents of the references cited within the references cited herein are also entire y incorporated by reference.
Reference to known method steps, conventional methods steps, known methods or conventional methods is not in any way an admission that any aspect, description or embodiment of the present invention is disclosed, taught or suggested in the relevant art.
The foregoing description of the specific embodiments will so fully reveal the general nature of the invention that others can, by applying knowledge within the skill of the art (including the contents of the references cited herein), readily modify and/or adapt for various applications such specific embodiments, without undue experimentation, without departing from the generic concept of the present invention. Therefore, such adaptations and modifications are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments, based on the teaching and guidance presented herein. It is to be understood that the phraseology or terminology herein is for the purpose of description and not of limitation, such that the terminology or phraseology of the present specification is to be interpreted by the skilled artisan in light of the teachings and guidance presented herein.
__________________________________________________________________________SEQUENCE LISTING(1) GENERAL INFORMATION:(iii) NUMBER OF SEQUENCES: 348(2) INFORMATION FOR SEQ ID NO:1:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 24 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:1:LeuSerLeuLeuLeuSerLeuLeuSerLeuLeuLeuSerLeuLeuSer151015LeuLeuLeuSerLeuTyrTyrTyr20(2) INFORMATION FOR SEQ ID NO:2:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 27 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:2:AspAspIlePheValThrLeuAspValLeuPheSerThrAlaSe rIle151015LeuAsnLeuSerAlaIleSerLeuLysLysLys2025(2) INFORMATION FOR SEQ ID NO:3:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 26 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:3:AspTyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheAsn15 1015CysProPheIleValThrLeuAsnIleLys2025(2) INFORMATION FOR SEQ ID NO:4:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 16 amino acids(B) TYPE: amino acid (C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:4:LysAlaValValTyrSerSerIleValSerPheTyrValPheIleAsp151015(2) INFORMATION FOR SEQ ID NO:5:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 27 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:5:AspCysAspValPheValPheValAspIleMetLeuCysThrAl aSer151015IlePheAsnLeuCysAlaIleSerValGlyLys2025(2) INFORMATION FOR SEQ ID NO:6:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 317 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:6:SerLeuValLeuLeuLeuPheAlaAspPheSerSerMetLeuGlyCys15 1015MetAlaValLeuIleGlyPheTrpArgLeuLysLeuLeuArgAsnHis202530ValThrLysValIle AlaCysPheCysAlaThrSerPheCysLysAsp354045PheProSerThrIleLeuThrLeuThrAsnThrAlaValAsnGlyGly50 5560PheProCysTyrLeuTyrAlaIleValIleThrTyrGlySerPheAla65707580CysTrpLeuTrpThrLe uIleCysLeuAlaIleSerIleTyrMetLeu859095IleValLysArgGluProGluProGluLeuPheGluLysTyrTyrTyr1 00105110LeuLeuCysTrpGlyLeuProLeuIleSerThrIleGlyLeuLysAsn115120125ThrValGlnPheVa lGlyAsnTrpCysTrpIleGlyValSerPheThr130135140GlyTyrArgPheGlyLeuPheTyrProPheLeuPheIleTrpAlaIle145 150155160SerAlaValLeuValGlyLeuThrSerArgTyrThrTyrTrpIleHis165170175AsnGlyV alSerAspAsnLysGluLysHisLeuThrTyrGlnPheLys180185190LeuIleAsnTyrIleIleValPheLeuValCysTrpValPheAlaVal 195200205ValAsnArgIleValAsnGlyLeuAsnTrpProProAlaLeuAsnIle210215220LeuHisThrTyr LeuSerValSerHisGlyPheTrpAlaSerValThr225230235240PheIleTyrAsnAsnProLeuMetTrpArgTyrPheGlyAlaLysIle 245250255LeuThrValPheThrPhePheGlyTyrPheThrAspValGlnLysLys260265270 LeuGluLysAsnLeuSerProTyrSerSerSerArgGlyThrSerGly275280285LysThrMetLeuGlyHisProThrGlyAspAspValGlnCysSerSer 290295300AspLeuGlnCysSerLeuGluArgHisProAsnMetVal305310315(2) INFORMATION FOR SEQ ID NO:7:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 349 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:7:ValTyrIleThrValGluLeuAlaIleAlaValLeuAlaThrLeuGly15 1015AsnValLeuValCysTrpAlaValTrpLeuAsnSerAsnLeuAsnVal202530ThrAsnTyrPheValVal SerLeuAlaAlaAlaAspIleAlaValGly354045ValIleAlaIleProPheAlaIleThrIleSerThrGlyPheCysAla50 5560AlaCysHisAsnCysLeuPhePheAlaCysPheValLeuValLeuThr65707580GlnSerSerIlePheSerLe uLeuAlaIleAlaIleAspArgTyrIle859095AlaIleArgIleProLeuArgTyrAsnGlyLeuValThrGlyThrArg100 105110AlaLysGlyIleIleAlaValCysTrpValLeuSerPheAlaIleGly115120125LeuThrProMetLeuGl yTrpAsnAsnCysSerGlnProLysGluGly130135140ArgAsnTyrSerGlnGlyCysGlyGluGlyGlnValAlaCysLeuPhe145150 155160GluAspValValProMetAsnTyrMetValTyrTyrAsnPhePheAla165170175PheValLeuV alProLeuLeuLeuValTyrLeuArgIlePheLeuAla180185190AlaArgArgGlnLeuLysGlnMetGluSerGlnProLeuProGlyGlu 195200205ArgAlaArgSerThrLeuGlnLysGluValHisAlaAlaLysSerAla210215220IleIleValGlyLeu PheAlaLeuCysTrpLeuProLeuHisIleIle225230235240AsnCysPheThrPhePheCysProGluCysSerHisAlaProLeuTrp 245250255LeuMetTyrLeuThrIleValLeuSerHisThrAsnSerTrpAsnPro260265270Phe IleTyrAlaTyrArgIleArgGluPheArgGlnThrPheArgLys275280285IleIleArgSerHisValLeuArgArgArgGluProPheLysAlaGly 290295300GlyThrSerAlaArgAlaLeuAlaAlaHisGlySerAspGlyGluGln305310315320Il eSerLeuArgLeuAsnGlyHisProProGlyValTrpAlaAsnGly325330335SerAlaProHisProGluArgArgProAsnGlyTyrThr 340345(2) INFORMATION FOR SEQ ID NO:8:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 314 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:8:AlaTyrIleGlyIleGluVa lLeuIleAlaLeuValSerValProGly151015TrpLeuValIleTrpAlaValLysValAsnGlnAlaLeuArgAspAla20 2530ThrPheCysPheIleValSerIleAlaValAlaAspValAlaValGly354045AlaLeuValIleProLeu AlaIleLeuIleAsnIleGlyProArgThr505560TyrPheHisThrCysLeuMetValAlaCysProValLeuIleLeuThr6570 7580GlnSerSerIleIleAlaLeuLeuAlaIleAlaValAspArgTyrLeu859095ArgValLysIlePr oLeuArgTyrLysThrValValThrProArgArg100105110AlaAlaValAlaIleAlaGlyCysTrpIleLeuSerPheValValGly115 120125LeuThrProLeuPheGlyTrpAsnArgLeuGlyGluAlaGlnArgAla130135140TrpAlaAlaAsnGlySerG lyGlyGluProValIleLysCysGluPhe145150155160GluLysValIleSerMetGluTyrMetValTyrPheAsnPhePheVal 165170175TrpValLeuProProLeuLeuLeuMetValLeuIleTyrLeuGluVal180185190PheTyr LeuIleArgArgGlnLeuGlyLysLysValSerAlaSerSer195200205GlyAspProGlnLysTyrTyrGlyLysGluLeuLysIleAlaLysSer21 0215220LeuAlaLeuIleLeuPheLeuPheAlaLeuSerTrpLeuProLeuHis225230235240IleIle AsnCysIleThrLeuPheCysProSerCysArgLysProSer245250255IleLeuMetTyrIleAlaIlePheLeuThrHisGlyAsnSerAlaMet 260265270ProIleValTyrAlaPheArgIleGlnLysPheArgValThrPheLeu275280285Ly sIleTrpAsnAspHisPheArgCysGlnProThrProProValAsp290295300GluAspProProGluGluAlaProHisAsp305310 (2) INFORMATION FOR SEQ ID NO:9:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 342 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:9:ValAlaPheIleGlyIleThrThrGlyLeuLeuSerIleAlaThrVa l151015ThrGlyAsnLeuLeuValLeuIleSerPheLysValAsnThrGluLeu20253 0LysThrValAsnAsnTyrPheLeuLeuSerIleAlaCysAlaAspLeu354045IleIleGlyThrPheSerMetLeuTyrLeuLeuMetHisTrpAla Leu505560GlyThrLeuAlaCysAspLeuTrpLeuAlaLeuAspTyrValAlaSer65707580AsnAlaSerValLeuAsnLeuLeuLeuIleSerPheAspArgTyrPhe859095SerValThrArgProLeuSerTyrArgAlaLysArgThrPr oArgArg100105110AlaAlaIleMetIleGlyIleAlaTrpLeuValSerPheValLeuTrp115120 125AlaProAlaIleLeuPheTrpGlnTyrLeuValGlyGluArgThrMet130135140LeuAlaGlyGlnCysTyrIleGlnPheLeuSerGlnProIleIleT hr145150155160PheGlyThrAlaMetAlaAlaPheTyrMetProValThrValMetThr165170 175LeuTyrTrpArgIleTyrArgPheThrGluAsnArgAlaArgGluLeu180185190GlnGlySerGluThrProGlyLysGlyGlyGly SerSerSerSerSer195200205GluArgSerGlnProGlyAlaGluGlySerProGluThrProLysGly210215 220GlnLysProArgGlyLysGluLeuAlaLysArgLysThrPheSerLeu225230235240ValLysGluLysLysAlaAlaArgThrLeuSer AlaIleLeuLeuAla245250255PheIleLeuThrTrpThrProTyrAsnIleMetValLeuValSerThr2602 65270PheCysLysAspCysValProGluThrLeuTrpGluLeuGlyTyrTrp275280285LeuIleCysTyrValAsnSerThrIleAs nProTrpTyrAlaLeuCys290295300AsnLysAlaPheArgAspThrPheArgLeuLeuLeuLeuCysTrpAsp305310 315320LysArgArgTrpArgLysIleProLysArgProGlySerValHisArg325330335ThrProSerArgGlnCys 340(2) INFORMATION FOR SEQ ID NO:10:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 317 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:10:ValValPheIleValLeuValAlaGlySer LeuSerLeuValThrIle151015IleGlyAsnIleLeuValMetValSerIleLysValAsnArgHisTyr20 2530PheLeuPheSerIleAlaCysAlaAspLeuIleIleGlyValPheSer354045MetAsnLeuTyrThrLeuTyrThrValIl eGlyTyrTrpProLeuGly505560ProValValCysAspLeuTyrValValSerAsnAlaSerValMetAsn65707 580LeuLeuIleIleSerPheAspArgTyrPheCysValThrLysProLeu859095ThrTyrProValLysArgThrThr LysMetAlaGlyMetMetIleAla100105110AlaAlaTrpValLeuSerPheIleLeuTrpAlaProAlaIleLeuPhe115 120125TrpGlnPheIleValGlyValArgThrValGluAspGlyGluCysTyr130135140IleGlnPhePheSerAsnProAlaValThr PheGlyThrAlaIleAla145150155160AlaPheTyrLeuProValIleIleMetIleValLeuTyrTrpHisIle165 170175SerArgAlaSerLysSerArgIleLysLysAspLysLysGluProVal180185190AlaAsnGlnAspProVa lSerProSerLeuValGlnGlyArgIleVal195200205LysProLeuSerSerAspAspLysIleValArgArgThrLysGlnPro210 215220AlaLysLysLysProProProSerArgGluLysLysValThrArgThr225230235240IleAlaIleLeuLeuA laPheIleIleThrTrpAlaProTyrAsnVal245250255MetValLeuIleAsnThrPheCysAlaProCysIleProAsnThrVal 260265270TrpArgIleGlyTyrTrpLeuCysTyrIleAsnSerThrIleAsnPro275280285AlaCysTyrAla LeuCysAsnAlaThrPheLysLysThrPheLysHis290295300LeuIleMetCysHisTyrLysAsnIleGlyAlaThrArg305310 315(2) INFORMATION FOR SEQ ID NO:11:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 355 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:11:TrpPheIleAlaPheLeuThrGlyIleLeuAla LeuValThrIleIle151015GlyAsnIleLeuValIleValSerPheLysValAsnLysGlnLeuLys2025 30ThrValAsnAsnTyrPheLeuLeuSerLeuAlaCysAlaAspLeuIle354045IleGlyValIleSerMetAsnLeuPheThrTh rTyrIleIleMetAsn505560ArgTrpAlaLeuGlyAsnThrAlaCysAspLeuTrpIleAlaIleAsp657075 80TyrValAlaSerAsnAlaSerValLeuAsnLeuLeuValIleSerPhe859095AspArgTyrPheSerIleThrArgPro LeuThrTyrArgAlaLysArg100105110ThrThrLysArgAlaGlyValMetIleGlyLeuAlaTrpValIleSer11512 0125PheValLeuTrpAlaProAlaIleLeuPheTrpGlnTyrPheValGly130135140LysArgThrValProProGlyGluCysPheIle GlnPheLeuSerGlu145150155160ProThrIleThrPheGlyThrAlaIleAlaAlaPheTyrMetProVal165 170175ThrIleMetArgIleLeuTyrTrpArgIleTyrLysGluThrGluLys180185190ArgThrLysGluLeuAlaGl yLeuGlnAlaSerGlyThrGluAlaGlu195200205ThrGluAsnPheValHisProThrGlySerSerArgSerCysSerSer210 215220TyrGluLeuGlnGlnGlnLysArgPheAlaLeuLysThrArgSerGln225230235240IleThrLysArgLysLeuL euValLysGluLysLysAlaAlaGlnThr245250255LeuSerAlaIleLeuLeuAlaPheIleIleThrTrpThrProTyrAsn260 265270IleMetValLeuValAsnThrPheCysAspSerCysIleProLysThr275280285TyrTrpAsnLeuGly GlyTyrTrpLeuCysTyrIleAsnSerThrVal290295300AsnProValCysTyrAlaLeuCysAsnLysThrPheArgThrThrPhe30531 0315320LysThrLeuLeuLeuCysGlnCysAspLysArgLysArgArgLysGln325330335GlnTyrGln GlnArgGlnSerValIlePheHisLysArgValProGlu340345350GlnAlaLeu355(2) INFORMATION FOR SEQ ID NO:12:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 333 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:12:MetValPheIleAlaThrValArgGlySerLeuSerLeuValThrVal15 1015ValGlyAsnIleLeuValMetLeuSerIleLysValAsnArgGlnLeu202530GlnThrValAsnAsnTyrPheLeu PheSerIleAlaCysAlaAspLeu354045IleIleGlyAlaPheSerMetAsnLeuTyrThrValTyrIleIleLys5055 60GlyTyrTrpProLeuGlyAlaTrpCysAspLeuTrpLeuAlaLeuAsp65707580TyrValValSerAsnAlaSerValM etLeuLeuIleIleSerPheAsp859095ArgTyrPheCysValThrLysProLeuThrTyrProAlaArgArgThr100 105110ThrLysMetAlaGlyIleMetIleAlaAlaAlaTrpValLeuSerPhe115120125ValLeuTrpAlaProAlaIleL euPheTrpGlnPheValValGlyLys130135140ArgThrValProAspAsnGlnCysPheIleGlnPheLeuSerAsnPro145150 155160AlaValThrPheGlyThrAlaIleAlaAlaPheTyrLeuProValVal165170175IleMetIleValLeu TyrIleHisIleSerLeuAlaSerArgSerArg180185190ValHisLysHisArgProGluGlyProLysGluLysLysAlaLysThr195 200205IleAlaPheLeuLysSerProIleMetGlnSerValLysLysProPro210215220ProGlyGluAlaLysPheAla SerIleAlaArgAsnGlnValArgLys225230235240LysArgGlnLeuAlaAlaArgGluArgLysValThrArgThrIlePhe 245250255AlaIleLeuLeuAlaPheIleLeuThrTrpThrProTyrAsnValMet260265270ValLeuVa lAsnThrPheCysGlnSerCysIleProAspThrValTrp275280285SerIleGlyTyrTrpLeuIleCysTyrValAsnSerThrIleAsnPro290 295300AlaCysTyrAlaLeuCysAsnAlaThrPheLysLysThrPheArgHis305310315320LeuLeuL euCysGlnArgTyrAsnIleGlyThrAlaArg325330(2) INFORMATION FOR SEQ ID NO:13:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 348 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear( ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:13:ValIleThrIleAlaValValThrAlaValValSerLeuMetThrIle151015ValGlyAsnValLeuValMetIl eSerPheLysValAsnSerGlnLeu202530LysThrValAsnAsnTyrTyrLeuLeuSerIleAlaCysAlaAspLeu35 4045IleIleGlyIlePheSerMetAsnLeuTyrThrThrTyrIleLeuIle505560MetGlyArgTrpAlaLeuGlySerLeuAla CysAspLeuTrpLeuAla65707580IleAspTyrValAlaSerAsnAlaSerValLeuAsnLeuLeuValIle85 9095SerPheAspArgTyrPheSerIleThrArgProLeuThrTyrArgAla100105110LysArgThrProLysArgA laGlyIleMetIleGlyIleAlaTrpLeu115120125IleSerPheIleLeuTrpAlaProAlaIleLeuCysTrpGlnTyrLeu130 135140ValGlyLysArgThrValProIleAspGluCysGlnIleGlnPheLeu145150155160SerGluProThrIleThr PheGlyThrAlaIleAlaAlaPheTyrIle165170175ProValSerIleMetArgIleLeuTyrCysArgIleTyrArgGluThr18 0185190GluLysArgThrLysAspLeuAlaAspLeuGlnGlySerAspSerVal195200205TyrLysAlaGluLys ArgLysProAlaHisArgAlaLeuPheArgSer210215220CysLeuArgCysProArgProThrLysGlyLeuAsnProAsnProSer2252 30235240HisGlnMetThrLysArgLysArgMetSerLeuValLysGluArgLys245250255AlaAlaGl nThrLeuSerAlaIleLeuLeuAlaPheIleIleThrTrp260265270ThrProTyrAsnIleMetValLeuValSerThrPheCysAspLysCys 275280285ValProValThrLeuTrpHisLeuGlyTyrTrpLeuCysTyrIleAsn290295300SerThrValAsnP roIleCysTyrAlaLeuCysAsnArgThrPheArg305310315320LysThrPheIleMetLeuLeuCysArgTrpLysLysLysLysValGlu 325330335GluLysLeuTyrTrpGlnGlyAsnSerLysLeuPro340345(2) INFORMATION FOR SEQ ID NO:14:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 377 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:14:ThrAlaGlyAspCysLeuIleMetLeuIleValLeuLeuIleValAla15 1015GlyAsnValLeuValIleValAlaIleAlaLysThrProArgLeuGln202530ThrLeuThrAsnLeuPheIleMe tSerIleAlaSerAlaAspLeuVal354045MetLeuLeuLeuValValProPheCysAlaThrLeuValValTrpGly5055 60ArgTrpGluTyrGlySerPhePheCysGluLeuTrpThrSerValAsp65707580ValLeuCysValThrAlaSerIle GluThrLeuCysValIleAlaLeu859095AspArgTyrLeuAlaIleThrSerProPheArgTyrGlnSerLeuLeu100 105110ThrArgAlaArgAlaArgGlyLeuValCysThrValTrpAlaIleSer115120125AlaLeuValSerPheLeuPro IleLeuLeuSerAspGluAlaArgArg130135140CysTyrAsnAspProLysCysCysAspPheValThrAsnArgAlaTyr145150 155160AlaIleAlaSerSerValValSerPheTyrValProLeuCysIleMet165170175PheValTyrLeuArg ValPheArgGluAlaGlnLysGlnValLysLys180185190IleAspSerCysGluArgArgPheLeuGlyGlyProAlaArgProPro195 200205SerProSerProSerProValProAlaProAlaProProGlyProPro210215220ArgProAlaAlaAlaAlaAl aThrAlaProLeuAlaAsnGlyArgAla225230235240GlyLysArgArgProSerArgLeuValAlaLeuArgGluGlnLysAla 245250255LeuLysThrLeuGlyIleIleMetGlyValPheThrLeuCysTrpLeu260265270ProPheP heHisArgGluLeuValProAspArgLeuPheValPhePhe275280285AsnTrpLeuArgTyrAlaAsnSerAlaPheAsnProIleIleTyrCys290 295300ArgSerProAspPheArgLysAlaPheGlnGlyLeuLeuCysCysAla305310315320ArgArg AlaAlaArgArgArgHisAlaThrHisGlyAspArgProArg325330335AlaSerGlyCysIleAlaArgProGlyProProSerProGlyAlaAla 340345350SerAspAspAspAspAspAspValValGlyAlaThrProProAlaArg355360365Leu LeuGluProTrpAlaGlyCysAsn370375(2) INFORMATION FOR SEQ ID NO:15:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 362 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:15:ValValGlyIleValMetSerLeuIleValLeuAlaIleValPheGly151015AsnValLeuValIleThrAlaIleAlaLysPheGluArg LeuGlnThr202530ValThrAsnTyrPheIleThrSerIleAlaCysAlaAspLeuValMet3540 45GlyLeuAlaValValProPheGlyAlaAlaHisIleLeuMetLysMet505560TrpThrPheGlyAsnPheTrpCysGluPheTrpThrSerIleAspVa l65707580LeuCysValThrAlaSerIleGluThrLeuCysValIleAlaValAsp8590 95ArgTyrPheAlaIleThrSerProPheLysTyrGlnSerLeuLeuThr100105110LysAsnLysAlaArgValIleIleIleMetValTrp IleValSerGly115120125LeuThrSerPheLeuProIleLeuTyrArgAlaThrHisGlnGluAla1301351 40IleAsnCysTyrAlaAsnGluThrCysCysAspPhePheThrAsnGln145150155160AlaTyrAlaAlaSerSerAlaValSerPheTyrVa lProLeuValIle165170175MetValPheValTyrSerArgValPheGlnGluAlaLysArgGlnLeu180185 190GlnLysIleAspLysSerGluGlyArgPheIlePheValGlnAsnLeu195200205SerGlnValGluGlnAspGlyArgThrGlyH isGlyLeuArgArgSer210215220SerLysPheCysLeuLysGluHisLysAlaLeuLysThrLeuGlyIle225230235 240IleProCysThrPheThrLeuCysTrpLeuProPhePheIleValAsn245250255IleValValIleGlnAspAsnLeu IleArgLysGluValTyrIleLeu260265270LeuAsnTrpIleGlyTyrValAsnSerGlyPheAsnProLeuIleTyr275 280285CysArgSerProAspPheArgIleAlaPheGlnGluLeuLeuCysLeu290295300ArgArgSerSerLeuLysAlaTyrGlyAsn GlyTyrSerSerAsnGly305310315320AsnThrGlyGluGlnSerGlyTyrHisValGluGlnGluLysGluAsn325 330335LysLeuLeuCysGluAspLeuProGlyThrGluAspPheValGlyHis340345350GlnGlyThrValProSe rAspAsnIleAsp355360(2) INFORMATION FOR SEQ ID NO:16:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 362 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:16:A laAlaLeuAlaGlyAlaLeuLeuAlaLeuAlaValLeuAlaThrVal151015GlyGlyAsnLeuLeuValIleValAlaIleAlaTrpThrProArgLeu202530GlnThrMetThrAsnValPheValThrSerLeuAlaAlaAlaAspLeu354045 AspLeuLeuValValProProAlaAlaThrLeuAlaLeuThrGlyHis505560TrpProLeuGlyAlaThrGlyCysGluLeuTrpThrSerValAspVal65 707580LeuCysValThrAlaSerIleGluThrLeuCysAlaIleAlaValAsp859095ArgTyrLeuAlaValThrAsnProLeuArgTyrGlyAlaLeuValThr100105110LysArgCysAlaArgThrAlaTrpLeuValTrpValValSerAl aAla115120125ValSerPheAlaProIleMetSerGlnTrpTrpArgValGlyAlaAsp130135140 AlaGluAlaGlnArgCysHisSerAsnProArgCysCysAlaPheAla145150155160SerAsnMetProTyrAlaValLeuLeuSerSerSerValSerP heTyr165170175LeuProLeuLeuLeuPheValTyrAlaArgValPheTrpAlaThrArg180185 190GlnLeuArgLeuLeuArgGlyGluLeuGlyArgPheProProGluGlu195200205SerProProAlaProSerArgSerLeuAlaProAlaPro ValGlyThr210215220GlyAlaProProGluGlyValProAlaCysGlyArgProProAlaArg225230235 240LeuIleProIleArgGluHisArgAlaLeuCysThrLeuGlyLeuIle245250255MetGlyThrPheThrLeuCysTrpLeuProPhe PheIleAlaAsnVal260265270LeuArgAlaLeuGlyGlyProSerLeuValProGlyProAlaPheLeu275280 285AlaLeuAsnTrpLeuIleGlyTyrAlaAsnSerAlaPheAsnProLeu290295300IleTyrCysArgSerProAspPheArgSerAlaPheAr gArgLeuLeu305310315320CysArgCysGlyArgArgLeuProProGluProCysAlaAlaAlaArg325 330335ProAlaLeuPheProSerGlyValProAlaAlaGluSerSerProAla340345350GlnProArgLeuCysGlnArgLeuA spGly355360(2) INFORMATION FOR SEQ ID NO:17:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 375 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:17:AlaIleLeu LeuGlyValIleLeuGlyGlyLeuIleLeuPheGlyVal151015LeuGlyAsnIleLeuValIleLeuSerValAlaCysHisArgHisLeu 202530HisSerValThrHisTyrTyrIleValAsnLeuAlaValAlaAspLeu354045LeuLeuTh rSerThrValLeuProPheSerAlaIlePheGluIleLeu505560GlyTyrTrpLysPheGlyArgValPheCysAsnValTrpAlaAlaVal65 707580AspValLeuCysCysThrAlaSerIleMetLeuLeuCysIleIleSer859095Ile AspArgTyrIleGlyValSerTyrProLeuArgTyrProThrIle100105110ValThrGlnLysArgGlyLeuMetAlaLeuLeuCysValTrpAlaLeu 115120125SerLeuValIleSerIleGlyProLeuPheGlyTrpArgGlnProAla130135140ProGluAsp GluThrIleCysGlnIleAsnGluGluProGlyTyrVal145150155160LeuPheSerAlaLeuGlySerPheTyrValProLeuThrIleIleLeu 165170175ValMetTyrCysArgValTyrValValAlaLysArgGluSerArgGly180185190 LeuLysSerGlyLeuLysThrAspLysSerAspSerGluGlnValThr195200205LeuArgIleHisArgLysAsnAlaGlnValGlyGlySerGlyValThr210215220SerAlaLysAsnLysThrHisPheSerValArgLeuLeuLysPheSer225230235240ArgGluLysLysAlaAlaLysThrLeuGlyIleValValGlyCysPhe245250255ValLeuCysTrpLeuProPhePheLeuValMetProIleGl ySerPhe260265270PheProAspPheArgProSerGluThrValPheLysIleAlaPheTrp275280 285LeuGlyTyrIleAsnSerCysIleAsnProIleIleTyrProCysSer290295300SerGlnGluPheLysLysAlaPheGlnAsnValLeuArgIleGlnC ys305310315320LeuArgArgLysGlnSerSerLysHisThrLeuGlyTyrThrLeuHis325330 335AlaProSerHisValLeuGluGlyGlnHisLysAspLeuValArgIle340345350ProValGlySerAlaGluThrPheTyrLysIle SerLysThrAspGly355360365ValCysGluTrpLysIlePhe370375(2) INFORMATION FOR SEQ ID NO:18:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 370 amino acids (B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:18:AlaIleSerValGlyLeuValLeuGlyAlaPheIleLeuPheAlaIle151 015ValGlyAsnIleLeuValIleLeuSerValAlaCysAsnArgHisLeu202530ArgThrProThrAsnTyrPheIleVal AsnIleAlaIleAlaAspLeu354045LeuLeuSerPheThrValLeuProPheSerAlaThrLeuGluValLeu5055 60GlyTyrTrpValLeuGlyArgIlePheCysAspIleTrpAlaAlaVal65707580AspValLeuCysCysThrAlaSerIleLe uSerLeuCysAlaIleSer859095IleAspArgTyrIleGlyValArgTyrSerLeuGlnTyrProThrLeu100 105110ValThrArgArgTyrAlaIleIleAlaLeuLeuSerValTrpValLeu115120125SerThrValIleSerIleGlyProLe uLeuGlyTrpLysGluProAla130135140ProAsnAspAspLysGluCysValThrGluGluProPheLeuPheCys145150 155160SerLeuGlySerPheTyrIleProIleAlaValIleLeuValMetTyr165170175CysArgValTyrIleValA laLysArgThrThrLysAsnLeuGluAla180185190GlyValMetLysGluMetSerAsnSerLysPheLeuThrLeuArgIle195 200205HisTrpSerLysAsnPheHisGluAspThrLeuSerSerThrLysAla210215220LysGlyHisAsnProArgSerSer IleAlaValLysLeuPheLysPhe225230235240SerArgGluLysLysAlaAlaLysThrLeuGlyIleValValGlyTrp24 5250255IleLeuCysTrpLeuProPhePheIleAlaLeuProLeuGlySerLeu260265270PheSerThrLeu LysProProAspAlaValPheLysTrpPheTrpLeu275280285GlyTyrPheAsnSerCysLeuAsnProIleIleTyrProCysSerSer290 295300LysGluPheLysArgAlaLeuLeuGlyCysGlnCysArgGlyGlyArg305310315320ArgArgArgAr gArgArgArgLeuAlaCysAlaTyrThrTyrArgPro325330335TrpThrArgGlyGlySerLeuGluArgSerGlnSerArgLysAspSer 340345350IleAspAspSerGlySerCysMetSerGlyGlnLysArgThrLeuPro355360365SerAla 370(2) INFORMATION FOR SEQ ID NO:19:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 330 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:19:ValAlaGlyLeuAlaAlaValValGlyPheLeu IleValPheThrVal151015ValGlyAsnValLeuValValIleAlaValLeuThrSerArgAlaLeu2025 30ArgAlaProGlnAsnLeuPheLeuValSerIleAlaSerAlaAspIle354045LeuValAlaThrLeuValMetProPheSerLe uAlaAsnGluIleMet505560TyrTrpTyrPheGlyGlnValTrpCysGlyValTyrLeuAlaIleAsp657075 80ValLeuPheCysThrSerSerIleValHisLeuCysAlaIleSerLeu859095AspArgTyrTrpSerValThrGlnAla ValGluTyrAsnLeuLysArg100105110ThrProArgArgValLysAlaThrIleValAlaValTrpLeuIleSer11512 0125AlaValIleSerPheProProLeuValSerLeuTyrArgGlnProAsp130135140GlyAlaAlaTyrProGlnCysGlyLeuAsnAsp GluThrTrpTyrIle145150155160LeuSerSerCysIleGlySerPhePheAlaProCysLeuIleTyrLeu165 170175LeuValTyrAlaArgIleTyrArgValAlaLysArgArgThrArgThr180185190LeuSerGluLysArgAlaPr oValGlyProAspGlyAlaSerProThr195200205ThrGluAsnGlyLeuGlyAlaAlaAlaGlyGluAlaArgThrGlyThr210 215220AlaArgPheLeuSerArgArgArgArgAlaArgSerSerValCysArg225230235240ArgLysValAlaGlnAlaA rgGluLysArgPheThrPheValLeuAla245250255LeuValPheValLeuCysTrpPheProPhePhePheIleTyrSerLeu260 265270TyrGlyIleCysArgGluAlaCysGlnValProGlyProLeuPheLys275280285PhePhePheTrpIle GlyTyrCysAsnSerSerLeuAsnProValIle290295300TyrThrValPheAsnGlnAspPheArgProSerPheLysHisIleLeu30531 0315320PheArgArgArgArgArgGlyPheArgGln325330(2) INFORMATION FOR SEQ ID NO:20:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 330 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:20:ThrAlaAlaIleAlaAlaAlaIleThrPheLeuIleLeuPheThrIle1510 15PheGlyAsnAlaLeuValIleIleAlaValLeuThrSerArgSerLeu202530ArgAlaProGlnAsnLeuPheLeuValSerIleAlaA laAlaAspIle354045LeuValAlaThrLeuIleIleProPheSerLeuAlaAsnGluLeuLeu505560GlyTyrTrpTyrPheArgArgThrTrpCysGluValTyrLeuAlaLeu65707580AspValLeuPheCysThrSerSerIleValHisLeuCys AlaIleSer859095LeuAspArgTyrTrpAlaValSerArgAlaLeuGluTyrAsnSerLys100105 110ArgThrProArgArgIleLysCysIleIleLeuThrValTrpLeuIle115120125AlaAlaValIleSerLeuProProLeuIleTyrLys GlyAspGlnGly130135140ProGlnProArgGlyArgProGlnCysLysLeuAsnGlnGluAlaTrp145150155 160TyrIleLeuSerSerIleGlySerPhePheAlaProCysLeuIleLeu165170175LeuValTyrLeuArgIleTyrLeuIleAl aLysArgSerAsnArgArg180185190GlyProArgAlaLysCysGlyProGlyGlnGlyGluSerLysGlnPro195200 205ArgProAspHisGlyGlyAlaIleAlaSerAlaLysLeuProAlaIle210215220AlaSerGlyArgGlyValGlyAlaIleGlyGlyG lnTrpTrpArgArg225230235240ArgAlaHisValThrArgGluLysArgPheThrPheValLeuAlaVal245 250255ValIleGlyValPheValLeuCysTrpPheProPhePhePheSerTyr260265270SerLeuGlyAlaIleCysPro LysHisCysLysValProHisGlyLeu275280285PheGlnPhePhePheTrpIleGlyTyrCysAsnSerSerLeuAsnPro29029 5300ValIleTyrThrIlePheAsnGlnAspPheArgMetPheArgArgIle305310315320LeuCysArgProTrpThrGln ThrAlaTrp325330(2) INFORMATION FOR SEQ ID NO:21:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 330 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:21: ThrLeuThrLeuValCysIleAlaCysLeuSerLeuThrValPheGly151015AsnValLeuValIleIleAlaValPheThrSerArgAlaLeuLys Ala202530ProGlnAsnLeuPheLeuValSerIleAlaSerAlaAspIleLeuVal354045 AlaThrLeuValIleProPheSerLeuAlaAsnGluValAsnGlyTyr505560TrpTyrPheGlyLysTrpCysGluIleTyrLeuAlaLeuAspValLeu 65707580PheCysThrSerSerIleValHisLeuCysAlaIleSerLeuAspArg85909 5TyrTrpSerIleThrGlnAlaIleGluTyrAsnLeuLysArgThrPro100105110ArgArgIleLysAlaIleIleIleThrValTrpValIleSer AlaVal115120125IleSerPheProProLeuIleSerIleGluLysLysGlyGlyGlyGly130135140 GlyProGlnProAlaGluProArgCysGluIleAsnAspGlnLysTrp145150155160TyrValIleSerSerCysIleGlySerPhePheAlaProCy sLeuIle165170175TrpLeuValTyrValArgIleTyrGlnIleAlaLysArgArgThrArg180185 190ValProProSerArgArgAspProAspAlaValAlaAlaProProGly195200205GlyThrGluArgArgProAsnGlyLeuGlyProGluA rgSerAlaGly210215220ProGlyGlyGlyArgGlyArgSerAlaSerGlyLeuProArgArgArg225230235 240AlaGlyAlaGlyGlyGlnAsnArgGluLysArgPheThrPheValIle245250255AlaValValIleGlyValPheValValCys TrpPheProPhePhePhe260265270ThrTyrThrLeuThrAlaValLeuCysSerValProArgThrLeuPhe275280 285LysPhePhePheTrpPheGlyTyrCysAsnSerSerLeuAsnProVal290295300IleTyrThrIlePheAsnHisAspPheArgArgAla PheLysLysIle305310315320LeuCysArgGlyAspArgLysArgIleVal325330(2) INFORMATION FOR SEQ ID NO:22: (i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 334 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:22:ThrLeuThrLeuValCysIleAlaGlyLeuIleMetLeuPheThrVal1 51015PheGlyAsnValLeuValIleIleAlaValPheThrSerArgAlaLeu202530Lys AlaProGlnAsnLeuPheLeuValSerIleAlaSerAlaAspIle354045LeuValAlaThrLeuValIleProPheSerLeuAlaAsnGluValMet 505560TyrTrpTyrPheGlyLysValTrpCysGluIleTyrLeuAlaIleAsp65707580ValL euPheCysThrSerSerIleValHisLeuCysAlaIleSerLeu859095AspArgTyrTrpSerIleThrGlnAlaIleGluTyrAsnLeuLysArg 100105110ThrProArgArgIleLysAlaIleIleValThrValTrpValIleSer115120125A laValIleSerPheProProLeuLeuIleSerIleGluLysLysGly130135140AlaGlyGlyGlyGlnGlnProAlaGluProSerCysLysIleAsnAsp145 150155160GlnLysTrpTyrValIleSerSerSerIleGlySerPhePheAlaPro165170175CysLeuIleAsnHisLeuValTyrValArgIleTyrGlnIleAlaLys180185190ArgArgThrArgValProProSerArgArgGlyProAspAlaC ysSer195200205AlaProProGlyGlyAlaAspArgArgProAsnAlaValGlyProGlu210215220 ArgGlyAlaGlyThrAlaGlyGlyGlnGlyGluGluArgAlaGlyGly225230235240AlaLysAlaSerArgTrpArgGlyArgGlnAsnArgGluLys ArgPhe245250255ThrPheValIleAlaValValIleGlyValPheValValCysTrpPhe260265 270ProPhePhePheThrTyrThrLeuIleAlaValGlyCysProValPro275280285TyrGlnLeuPheAsnPhePhePheTrpPheGlyTyrCys AsnSerSer290295300LeuAsnProValIleTyrThrIlePheAsnHisAspPheArgArgAla305310315 320PheLysLysIleLeuCysArgGlyAspArgLysArgIleVal325330(2) INFORMATION FOR SEQ ID NO:23:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 321 amino acids(B) TYPE: amino acid (C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:23:LeuLeuThrAlaLeuValLeuSerValIleIleValLeuThrIleIle151015 GlyAsnIleLeuValIleLeuSerValPheThrTyrLysProLeuArg202530IleValGlnAsnPhePheIleValSerIleAlaValAlaAspLeuThr354045ValAlaLeuLeuValLeuProPheTrpAlaTyrSerIleLeuGlyArg505560TrpGlu PheGlyIleHisLeuCysLysLeuTrpLeuThrCysAspVal65707580LeuCysCysThrSerSerIleLeuAsnLeuCysAlaIleAlaLeuAsp 859095ArgTyrTrpAlaIleThrAspProIleAsnTyrAlaGlnLysArgThr100105110ValGlyArgValLeuLeuLeuIleSerGlyValTrpLeuLeuSerLeu115120125LeuIleSerSerProProLeuIleGlyTrpAsnAspTrpProAspGl u130135140PheThrSerAlaThrProCysGluLeuThrSerGlnArgIleGlyTyr145150155160ValIleTyrSerSerLeuGlySerPhePheIleProIleAlaIleMet165170175ArgIleValTyrIleGluIlePheValAlaThrArgArgA rgLeuArg180185190GluArgAlaArgAlaAsnLysIleAsnThrIleAlaLeuLysSerThr195200 205GluLeuGluProMetAlaAsnSerSerProValAlaAlaSerAsnSer210215220GlySerLysLysLysThrSerGlyValAsnGlnPheIleGluGlu Lys225230235240GlnLysIleSerLeuSerLysGluArgArgAlaAlaArgThrLeuGly245250 255IleIleMetValPheValIleCysTrpLeuProPhePheIleMetTyr260265270ValIleLeuProPheCysCysProThrAsnLys PheLysAsnPheIle275280285ThrTrpLeuGlyTyrIleAsnSerGlyLeuAsnProValIleTyrThr290295 300IlePheAsnLeuAspTyrArgArgAlaPheLysArgLeuLeuGlyLeu305310315320Asn(2) INFORMATION FOR SEQ ID NO:24:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 373 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:24:ArgIleLeuThrAlaCysPheLeuSerLeuLeuIleLeuSerThrLeu15 1015LeuGlyAsnThrLeuValCysAlaAlaValIleArgPheArgHisLeu202530ArgSerLysValThrAsn PhePheValIleSerLeuAlaValSerAsp354045LeuLeuValAlaValLeuLeuTrpLysAlaValAlaGluIleAlaGly50 5560PheTrpProPheGlySerPheCysAsnIleTrpValAlaPheAspIle65707580MetCysSerThrAlaSerIl eLeuAsnLeuCysValIleSerValAsp859095ArgTyrTrpAlaIleSerSerProPheArgTyrGluArgLysLysArg100 105110ProLysAlaAlaPheIleLeuIleSerValAlaTrpThrLeuSerVal115120125LeuIleSerPheIlePr oValGlnLeuSerTrpHisLysAlaLysPro130135140ThrSerProSerAspGlyMetAlaThrSerLeuAlaGluThrIleAsp145150 155160AsnCysAspSerSerLeuSerArgThrTyrAlaIleSerSerSerVal165170175IleSerPheT yrIleProValAlaIleLeuValThrTyrThrArgIle180185190TyrArgIleAlaGlnLysGlnIleArgArgIleAlaAlaLeuGluArg 195200205AlaAlaValHisAlaLysAsnCysGlnGlyAsnLysProValGluCys210215220SerGlnProGluSer SerPheMetSerPheLysArgGluThrLysVal225230235240LeuLysThrLeuSerValIleThrCysValPheValCysCysTrpLeu 245250255ProPhePheIleLeuAsnCysIleLeuProPheCysGlySerGlyGlu260265270Thr GlnProPheCysThrAspSerAsnThrPheAspValPheValTrp275280285PheGlyTrpAlaAsnSerSerLeuAsnProIleIleTyrAlaPheAsn 290295300AlaAspPheArgLysAlaPheSerThrLeuLeuGlyCysTyrArgLeu305310315320Cy sProAlaThrAsnMetAlaIleGluThrValSerIleAsnAsnGly325330335AlaAlaMetPheSerSerHisHisGluProArgGlySerIleSerLys340345350GluCysAsnLeuValTyrLeuIleProHisAlaValGlySerSerGlu355360365 AspLeuLysLysGlu370(2) INFORMATION FOR SEQ ID NO:25:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 360 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:25:GlnTrpThrAlaCys LeuLeuThrLeuLeuIleIleTrpThrLeuLeu151015GlyAsnValLeuValCysAlaAlaIleValArgSerArgHisLeuLeu 202530ValPheIleValSerIleAlaValSerAspLeuPheValAlaLeuLeu354045ValAsnThrTrpLy sAlaTyrAlaGluValAlaGlyTyrTrpProPhe505560GlyAlaPheCysAspValTrpValAlaPheAspIleMetCysSerThr657 07580AlaSerIleLeuAsnLeuCysValIleSerValAspArgTyrTrpAla859095IleSerArg ProPheArgTyrLysAlaLeuValMetValGlyIleAla100105110TrpThrLeuSerIleLeuIleSerPheIleProValGlnIleAsnTrp 115120125AsnArgAspGlnAlaAlaSerTrpGlyGlyLeuAspLeuProAsnAsn130135140IleAspCysAspSer SerLeuAsnArgThrTyrAlaIleSerSerSer145150155160LeuIleSerPheTyrIleProValAlaIleLeuValThrTyrThrArg 165170175IleTyrArgIleAlaGlnValGlnIleArgArgIleSerSerLeuGlu180185190Ar gAlaAlaGluHisAlaGlnSerCysArgSerSerAlaAlaCysAla195200205ProAspThrSerLeuArgAlaSerIleLysLysGluThrLysValLeu 210215220LysThrLeuSerValIleIleCysValPheValCysCysTrpLeuPro225230235240P hePheIleLeuAsnCysMetValProPheCysSerGlyHisProGlu245250255GlyProProAlaGlyPheProCysValSerGluThrThrPheAspVa l260265270PheValTrpPheGlyTrpAlaAsnSerSerLeuAsnProValIleTyr275280285 AlaPheAsnAlaAspPheGlnLysValPheAlaGlnLeuLeuCysSer290295300HisPheCysSerArgThrProValGluThrValAsnIleSerAsnGlu 305310315320LeuIleSerTyrAsnGlnAspIleValPheHisLysGluIleAlaAla325330 335AlaTyrIleHisMetMetProAsnAlaValThrProGlyAsnArgGlu340345350ValAspAsnAspGluGluGluGly355 360(2) INFORMATION FOR SEQ ID NO:26:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 314 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:26:TyrAsnTyrTyrAlaThrLeuLeuThrLeu LeuIleAlaValIleVal151015PheGlyAsnValLeuValCysMetAlaValSerArgGluLysAlaLeu20 2530GlnThrMetAsnTyrLeuIleValSerIleAlaValAlaAspLeuLeu354045ValAlaThrLeuValTrpTrpTrpTyrL euGluValValGlyGluTrp505560LysPheSerArgIleHisCysAspIlePheValThrLeuAspIleThr6570 7580AlaSerIleLeuAsnLeuCysAlaIleSerIleAspArgTyrThrAla859095ValAlaMetProMetLeuTyrAsn ThrArgTyrSerSerLysArgArg100105110ValThrValMetIleSerIleValTrpValLeuSerPheThrIleSer115 120125CysProLeuLeuPheGlyLeuAsnAsnAlaAspGlnAsnGluCysIle130135140IleAlaAsnProAlaPheValValTyrSe rSerIleValSerPheTyr145150155160ValProPheIleValThrLeuLeuValTyrIleLysIleTyrIleVal165 170175LeuArgArgArgArgLysArgValAsnThrLysArgSerSerArgAla180185190PheArgAlaHisLeuA rgAlaProLeuLysGlyAsnCysThrHisPro195200205GluAspMetLysLeuCysThrValIleProAsnGlyLysThrArgThr210 215220SerLeuLysThrMetSerArgArgLysLeuSerGlnGlnLysGluLys225230235240LysAlaThrGlnMet IleAlaIleValLeuGlyValPheIleIleCys245250255LysLeuProPhePheIleThrHisIleLeuAsnIleHisCysAspCys 260265270AsnIleProProValLeuTyrSerAlaPheThrTrpLeuGlyTyrVal275280285AsnSerAlaVal AsnProIleIleTyrThrThrPheAsnIleGluPhe290295300ArgLysAlaPheLeuLysIleLeuHisCys305310(2) INFORMATION FOR SEQ ID NO:27: (i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 317 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:27:AlaTyrTyrAlaLeuSerTyrCysAlaLeuIleLeuAlaIleValPhe1 51015GlyAsnGlyLeuValCysMetAlaValLeuArgGluLysAlaLeuGln202530Thr ThrThrAsnTyrLeuValValSerLeuAlaValAlaAspLeuLeu354045ValAlaThrLeuValTrpTrpValValTyrLeuGluValThrGlyGly 505560ValTrpAsnPheSerArgIleCysCysAspValPheValThrLeuAsp65707580ValM etMetThrAlaSerIleLeuAsnLeuCysAlaIleSerIleAsp859095ArgTyrThrAlaValHisTyrGlnHisGlyThrGlyGlnSerSerCys 100105110ArgArgValAlaIleMetIleThrAlaValTrpValLeuAlaPheAla115120125V alSerCysProLeuLeuPheGlyPheAsnThrGlyAspProThrVal130135140CysSerIleSerAsnProAspPheValIleTyrSerSerValValSer145 150155160PheTyrLeuProPheGlyValThrValLeuValTyrAlaArgIleTyr165170175ValValLeuLysGlnArgArgArgLysArgIleLeuThrArgGlnAsn180185190SerGlnCysAsnSerValArgProGlyPheProGlnGlnSerT hrSer195200205LeuProAspProAlaHisLeuGluLeuLysArgSerAsnGlyArgLeu210215220 SerThrSerLeuLysLeuProLeuGlnProArgGlyValProLeuArg225230235240GluLysLysAlaThrGlnMetValAlaIleValLeuGlyAla PheIle245250255ValCysTrpLeuProPhePheLeuThrHisValIleAsnThrHisCys260265 270GlnThrCysHisValSerProGluLeuTyrSerAlaThrThrTrpLeu275280285GlyTyrValAsnSerAlaLeuAsnProValIleTyrThr ThrPheAsn290295300IleGluPheArgLysAlaPheLeuLysIleLeuSerCys305310315(2) INFORMATION FOR SEQ ID NO:28: (i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 315 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:28:GlyAlaAlaAlaLeuValGlyGlyValLeuLeuIleCysAlaValLeu1 51015AlaGlyAsnSerLeuValCysValSerValAlaThrGluArgAlaLeu202530GlnThr ProThrAsnSerPheIleValSerLeuAlaAlaAlaAspLeu354045LeuLeuAlaLeuLeuValLeuProLeuPheValTyrSerGluValGln50 5560GlyAlaAlaTrpLeuLeuSerProArgLeuCysAspValMetLeuCys65707580ThrAlaS erIlePheAsnLeuCysAlaIleSerValAspArgPheVal859095AlaValAlaValProLeuArgTyrAsnArgGlnGlyGlySerArgArg 100105110GlnLeuLeuLeuIleGlyAlaThrTrpLeuLeuSerAlaAlaValAla115120125AlaP roValLeuCysGlyLeuAsnAspValArgGlyArgAspProAla130135140ValCysArgLeuGluAspArgAspTyrValValTyrSerSerValCys145 150155160SerPhePheLeuProCysProLeuLeuTyrTrpAlaThrPheArgGly165170175 LeuGlnLeuValAlaArgArgAlaLysLeuHisGlyArgAlaProArg180185190ArgProSerGlyProGlyProProSerProThrProProAlaProA rg195200205LeuProGlnAspProCysGlyAlaLeuProProGlnThrProProGln210215220Thr ArgArgArgArgArgAlaLysIleThrGlyArgGluArgLysAla225230235240MetArgValLeuProValValValGlyAlaPheIleLeuCysTrp Thr245250255ProPhePheValValHisIleThrGlnAlaLeuCysProAlaCysSer260265 270ValProProArgLeuValSerAlaValThrTrpLeuSerTyrValAsn275280285SerAlaIleAsnProValIleTyrThrValPheAsnAlaGlu PheArg290295300AsnValPheArgLysAlaLeuArgAlaCysCys305310315(2) INFORMATION FOR SEQ ID NO:29:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 327 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:29:LysIleSerLeuAlaValValLeuSerValIleThrLeuAlaThrVal15 1015LeuSerAsnAlaPheValLeuThrArgIleLeuLeuThrArgLysLeu202530HisThrProAlaAsn TyrLeuIleGlySerIleAlaThrThrAspLeu354045LeuValSerIleLeuValTrpIleSerIleAlaTyrThrIleThrHis50 5560ThrTrpAsnPheGlyGlnIleLeuCysAspIleTrpLeuSerSerAsp65707580IleThrCysCysThrA laSerIleLeuHisLeuCysValIleAlaLeu859095AspArgTyrTrpAlaIleThrAspAlaLeuGluTyrSerLysArgArg 100105110ThrAlaGlyHisAlaAlaThrMetIleAlaIleValTrpAlaIleSer115120125IleCysIleSerI leProProLeuPheTrpArgAlaLysAlaGlnGlu130135140GluMetSerAspCysLeuValAsnThrSerGlnSerTyrThrIleTyr145 150155160SerThrCysGlyAlaPheTyrIleProSerValLeuLeuIleIleLeu165170175TyrGly ArgIleTyrArgAlaAlaArgAsnArgIleLeuAsnProPro180185190SerLeuTyrGlyLysArgPheThrThrAlaHisLeuIleThrGlySer 195200205AlaGlySerSerLeuCysSerLeuAsnSerSerLeuHisGluGlyHis210215220AsnHisValLys IleLysLeuAlaAspSerAlaLeuGluArgLysArg225230235240IleSerAlaAlaArgGluArgLysAlaThrLysIleLeuGlyIleIle 245250255LeuGlyAlaPheIleIleCysTrpLeuProPhePheValValSerLeu260265270 ValLeuProIleCysArgAspSerCysTrpIleHisProAlaLeuPhe275280285AspPhePheThrTrpLeuGlyTyrIleAsnSerLeuIleAsnProIle 290295300IleTyrThrValPheAsnGluGluPheArgGlnAlaPheGlnLysIle305310315320 ValProPheArgLysAlaSer325(2) INFORMATION FOR SEQ ID NO:30:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 325 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:30: ValIleThrSerLeuLeuLeuGlyThrLeuIlePheCysAlaValLeu151015GlyAsnAlaCysValValAlaAlaIleAlaLeuGluArgSerLeuGl n202530AsnValAlaAsnTyrLeuIleGlySerLeuAlaValArgAspLeuMet354045 ValSerValLeuValLeuProMetAlaAlaLeuTyrGlnValLeuAsn505560LysTrpThrLeuGlyGlnValThrCysAspLeuPheIleAlaLeuAsp6 5707580ValLeuCysCysThrSerSerIleLeuHisLeuCysAlaIleAlaLeu859095AspArgTyrTrpAlaIleThrAspProIleAspTyrValAsnLysArg100105110ThrProArgProArgAlaLeuIleSerLeuThrTrpLeuIleG lyPhe115120125LeuIleSerIleProProMetLeuGlyTrpArgThrProGluAspArg130135140 SerAspProAspAlaCysThrIleSerLysAspHisGlyTyrThrIle145150155160TyrSerThrIlePheAlaPheTyrIleProLeuLeuLeuMet LeuVal165170175LeuTyrGlyArgIlePheArgAlaAlaArgPheArgIleArgLysThr180185 190ValLysLysValGluLysThrGlyAlaAspThrArgHisGlyAlaSer195200205ProAlaProGlnProLysLysSerValAsnGlyGluSer GlySerArg210215220AsnAlaSerPheGluArgLysAsnGluArgAsnAlaPheAlaLysLeu225230235 240LeuAlaArgGluArgLysThrValLysThrLeuGlyIleIleMetThr245250255PheIleLeuCysTrpLeuProPhePheIleVa lAlaLeuValLeuPro260265270PheCysGluSerSerCysHisMetProThrLeuIleArgAlaIleIle275280 285AsnTrpLeuCysValIleAsnSerLeuLeuAsnProValIleTyrAla290295300TyrPheAsnLysAspPheGlnAsnAlaPheLysLysI leIleLysCys305310315320AsnPheCysArgGln325(2) INFORMATION FOR SEQ ID NO:31:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 385 amino acids (B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:31:GlnAsnTrpProAlaLeuSerIleValValIleIleIleAsnThrIle1510 15GlyGlyAsnIleLeuValIleMetAlaValSerLysLysLeuHisAsn202530AlaThrAsnTyrPheLeuMetSerIleAlaIleA laAspMetLeuVal354045GlyPheLeuValTrpLeuSerLeuLeuAlaIleLeuTyrAspTyrVal5055 60TrpProLeuProArgTyrLeuCysProValTrpIleSerLeuAspVal65707580LeuPheSerThrAlaSerIleMetHisLeuCysAla IleSerLeuAsp859095ArgTyrValAlaIleArgAsnProIleGluHisSerArgPheSerArg100105 110ThrLysAlaIleMetLysIleAlaIleValTrpAlaIleSerIleGly115120125ValSerValProIleProValIleGlyLeuArg AspGluSerLysVal130135140PheValAsnAsnThrThrIleCysValLeuAsnAspProAsnPheVal145150155 160LeuIleGlySerPheValAlaPhePheIleProThrLeuIleMetVal165170175IleThrTyrPheLeuThrIleTyrVa lLeuArgArgGlnThrLeuMet180185190LeuLeuArgGlyHisThrGluGluGluIleAlaMetSerLeuAsnPhe195 200205LeuAsnCysCysCysLysLysAsnGlyGlyGluGluGluAsnAlaPro210215220AsnAsnProAsnProAspGlnLysProArgA rgLysLysLysGluLys225230235240ArgProArgGlyThrMetGlnAlaIleAsnAsnGluLysLysAlaSer245 250255LysValLeuGlyIleValPhePheValPheLeuIleMetTrpCysPro260265270PhePheIleThrAsnIle LeuSerValLeuCysGlyLysAlaCysAsn275280285GlnCysLysLeuLeuAsnValPheValTrpIleGlyTyrValCysSer290 295300GlyIleAsnProValIleTyrThrLeuPheAsnLysIleTyrArgArg305310315320AlaPheSerLysTyrLeu ArgCysAspTyrLysProAspLysLysPro325330335ProValArgGlnIleProArgValAlaAlaThrAlaLeuSerGlyArg3 40345350GluLeuAsnValAsnIleTyrArgHisThrAsnGluArgValAlaArg355360365LysAlaAsnAspPr oGluProGlyIleGluAsnGlnValGluAsnLeu370375380Glu385(2) INFORMATION FOR SEQ ID NO:32:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 379 amino acids(B) TYPE: amino acid (C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:32:LysAsnTrpSerAlaLeuLeuThrThrValValIleIleLeuThrIle151015 AlaGlyAsnIleLeuValIleMetAlaValSerLeuGluLysLysLeu202530GlnAsnAlaThrAsnTyrPheLeuMetSerLeuAlaIleAlaAspM et354045LeuLeuGlyPheLeuValTrpValSerAsnGluThrIleLeuTyrGly505560TyrA rgTrpProLeuProSerLysLeuCysAlaIleTrpIleTyrLeu65707580AspValLeuPheSerThrAlaSerIleMetHisLeuCysAlaIleSer859095LeuAspArgTyrValAlaIleGlnAsnProIleHisHisSerArgPhe10010511 0AsnSerArgThrLysAlaPheLeuLysIleIleAlaValTrpThrIle115120125SerValGlyIleSerMetProIleProValPheGlyLeuGlnAsp Asp130135140SerLysValPheLysGluGlySerCysLeuLeuAlaAspAspAsnPhe1451501551 60ValLeuIleGlySerPheValAlaPhePheIleProLeuThrIleMet165170175ValIleThrTyrPheLeuThrIleLysSerLeuArgGl nLysPheAla180185190ThrLeuCysValSerAspLeuSerThrArgAlaLysLeuAlaSerPhe195200 205SerPheLeuProGlnSerSerLeuSerSerGluLysLeuPheGlnArg210215220SerIleHisArgGluProGlySerTyrAlaGlyArgLysThrM etGln225230235240SerIleSerAsnGluGlnLysAlaCysLysValLeuGlyIleValPhe245250 255PheLeuPheValValMetTrpCysProPhePheIleThrAsnIleMet260265270ValIleCysLysGluSerCysAsnGluAsn ValIleGlyAlaLeuLeu275280285AsnValPheValTrpIleGlyTyrLeuSerSerAlaValAsnProLeu290295 300ValTyrThrLeuPheAsnLysThrTyrArgSerAlaPheSerArgTyr305310315320LeuGlnCysGlnTyrLysGluAsnArgLys ProLeuLeuIleLeuVal325330335AsnThrIleProAlaLeuAlaTyrLysSerSerGlnLeuGlnValGly340 345350GlnLysLysAsnSerGlnGluAspAlaGluGlnThrValAspAspCys355360365SerMetValThrLeuGlyLysGlnGl nSerGlu370375(2) INFORMATION FOR SEQ ID NO:33:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 337 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:33:IleThrIleT hrValValLeuAlaValLeuIleLeuIleThrValAla151015GlyAsnValValValCysIleAlaValGlyIleAsnArgArgLeuArg 202530AsnLeuThrAsnCysPheIleValSerLeuAlaIleThrAspLeuLeu354045LeuGlyLeu LeuValLeuProPheSerAlaIleTyrGlnLeuSerCys505560LysTrpSerPheGlyLysValPheCysAsnIleTyrThrSerLeuAsp65 707580ValMetLeuCysThrAlaSerIleLeuAsnLeuLeuIleSerLeuAsp859095ArgT yrCysAlaValMetAspProLeuArgTyrProValLeuValArg100105110ProValArgValAlaIleSerLeuValLeuIleTrpValIleSerIle 115120125ThrLeuSerPheLeuSerIleHisLeuGlyTrpAsnSerArgAsnGlu130135140ThrSerLys GlyAsnHisThrThrSerLysCysLysValGlnValAsn145150155160GluValTyrGlyLeuValAspGlyLeuValThrPheTyrLeuProLeu 165170175LeuIleMetCysIleThrTyrTyrArgIlePheLysValAlaArgAsp180185190 AlaLysArgAsnHisIleSerSerTrpLysAlaAlaThrIleArgGlu195200205HisLysAlaThrValThrIleAlaAlaValMetAlaPheIleIleCys210215220TrpPheProTyrPheThrAlaPheValTyrArgGlyLeuArgGlyAsp225230235240 AspAlaIleAsnGluValLeuGluAlaIleValLeuTrpLeuGlyTyr245250255AlaAsnSerAlaLeuAsnProIleLeuTyrAlaAlaLeuAsn ArgAsp260265270PheArgThrGlyTyrGlnGlnLeuPheCysCysArgIleAlaAsnArg2752802 85AsnSerHisLysThrSerLeuArgSerAsnAlaSerGlnLeuSerArg290295300ThrGlnSerArgGluProArgGlnGlnGluGluLysProLeuLysLe u305310315320GlnValTrpSerGlyThrGluValThrAlaProGlnGlyAlaThrAsp325330 335Arg(2) INFORMATION FOR SEQ ID NO:34:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 315 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:34:IleIleThrTyrLeuValPheAlaVa lArgPheValLeuGlyValLeu151015GlyAsnGlyLeuValIleTrpValAlaGlyPheArgMetThrHisThr20 2530ValThrThrIleSerTyrLeuAsnLeuAlaValAlaAspPheCysPhe354045ThrSerThrLeuProPhePheMet ValArgLeuGlyHisTrpProPhe505560GlyTrpPheLeuCysLysPheLeuPheThrIleValAspIleAsnLeu6570 7580PheGlySerValPheLeuIleAlaLeuIleAlaLeuAspArgCysVal859095CysValLeuHisProValTr pThrGlnAsnHisArgThrValSerLeu100105110AlaLysLysValIleIleGlyProTrpValMetAlaLeuLeuLeuThr115 120125LeuProValIleIleArgValThrIleValProGlyLysThrGlyThr130135140ValAlaCysThrPheAsnPheSerP roTrpThrAsnAspProLysGlu145150155160ArgIleAsnValAlaValAlaMetLeuThrValArgGlyIleIleArg165 170175PheIleIleGlyPheSerAlaProMetSerIleValAlaValSerTyr180185190GlyLeuIleAla ThrLysIleIleLysSerSerArgProLeuArgVal195200205LeuSerPheValAlaAlaAlaPhePheLeuCysTrpSerProTyrGln210 215220ValValAlaLeuIleAlaThrValArgIleArgGluLeuLeuGlnGly225230235240MetTyrLysGlu IleGlyIleAlaValAspValThrSerAlaIleAla245250255PhePheAsnSerCysLeuAsnProLeuTyrValPheMetGlyGlnAsp 260265270PheArgGluArgLeuIleHisAlaLeuProAlaSerLeuGluArgAla275280285LeuThrGl uAspSerThrGlnThrSerAspThrAlaThrAsnSerThr290295300LeuProSerAlaGluValAlaLeuGlnAlaLys305310 315(2) INFORMATION FOR SEQ ID NO:35:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 304 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:35:AspIleLeuAlaLeuValIlePheAlaValValPh eLeuValGlyVal151015LeuGlyAsnAlaLeuValValTrpValThrAlaPheGluAlaLysArg2025 30ThrIleAsnAlaIleTrpPheLeuAsnIleAlaValAlaAspPheLeu354045SerCysLeuAlaLeuProIleLeuPheThrSer IleValGlnHisHis505560HisTrpProPheGlyGlyAlaAlaCysSerIleLeuProSerLeuIle657075 80LeuLeuAsnMetTyrAlaSerIleLeuLeuLeuAlaThrIleSerAla859095AspArgPheLeuLeuValPheLysProIl eTrpCysGlnAsnPheArg100105110GlyAlaGlyLeuAlaTrpIleAlaCysAlaValAlaTrpGlyIleAla115120 125LeuLeuLeuThrIleProSerPheLeuTyrArgValValArgGluGlu130135140TyrPheProProLysValLeuCysGlyCysAspT yrSerHisAspLys145150155160ArgArgGluArgAlaValAlaIleValArgLeuValLeuGlyPheLeu165 170175TrpProLeuLeuThrLeuThrIleCysTyrThrThrArgSerThrLys180185190ThrLeuLysValValValAla ValValAlaSerPhePheIlePheTrp195200205LeuProTyrGlnValThrGlyIleMetMetSerPheLeuGluProSer21021 5220SerProThrPheLeuLeuLeuAsnLysLeuAspSerLeuCysValSer225230235240PheAlaTyrIleAsnCysCys IleAsnProIleIleTyrValValAla245250255GlyGlnGlyGlnPheGlnGlyArgLeuArgLysSerLeuProSerLeu260 265270LeuArgAsnValLeuThrGluGluSerValValArgGluSerLysSer275280285PheThrArgSerThrVa lAspThrMetAlaGlnLysThrGlnAlaVal290295300(2) INFORMATION FOR SEQ ID NO:36:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 322 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:36:ThrLeuPheValProSerValTyrThrGlyValPheValValSerLeu151015ProLeuAsnIleMetAla IleValValPheIleLeuLysMetLysVal202530LysLysProAlaValHisIleAlaThrAlaAspValLeuPheValSer35 4045ValLeuProPheLysIleSerTyrTyrPheSerGlySerAspTrpGln505560PheGlySerGluLeuCysArgPheV alThrAlaAlaPheTyrCysAsn65707580MetTyrAlaSerIleLeuLeuIleSerIleAspArgPheIleAlaVal85 9095ValTyrProMetGlnSerLeuSerTrpArgThrLeuGlyArgAlaSer100105110PheThrCysIleAl aIleTrpAlaIleAlaIleAlaGlyValProLeu115120125ValLeuLysGluGlnThrIleGlnValProGlyLeuAsnIleThrThr130 135140IleCysHisAspValLeuAsnGluThrLeuLeuGluGlyTyrTyrAla145150155160TyrTyrPheSerA laPheSerAlaValPhePhePheValProLeuIle165170175IleSerThrValCysTyrValSerIleIleArgCysLeuSerSerSer 180185190AlaValAlaAsnArgSerLysLysSerArgThrAsnArgCysPheAsn195200205SerThrVal AlaLeuPheLeuSerAlaAlaValPheCysIlePheIle210215220IleCysPheGlyProThrTrpLeuLeuIleAlaHisTyrSerPheLeu225 230235240SerHisThrSerThrThrGluAlaAlaTyrPheAlaTyrLeuLeuCys245250255Val CysValSerSerIleSerSerCysIleAspProLeuIleTyrTyr260265270TyrAlaSerSerGluCysGlnArgTyrValTyrSerIleLeuCysCys 275280285LysGluSerSerAspProSerSerTyrAsnSerSerGlyGlnLeuMet290295300SerLeuTh rCysSerSerAsnLeuAsnAsnSerIleTyrLysLysLeu305310315320LeuThr(2) INFORMATION FOR SEQ ID NO:37:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 311 amino acids (B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:37:TyrIleAsnThrValIleSerCysThrIlePheIleValGlyTrpGly1510 15AsnAlaThrLeuLeuArgIleIleTyrGlnAsnLysCysMetArgAsn202530GlyProAsnAlaLeuIleAlaSerIleAlaLeuG lyAspLeuIleTyr354045ValValIleAspLeuProIleAsnValProLysLeuIleAlaGlyArg5055 60TrpProPheGluGlnAsnAspPheGlyValPheCysLysPheMetGly65707580ValValMetIlePhePheGlyLeuSerProLeuLeu LeuGlyAlaAla859095MetAlaSerGluArgTyrLeuGlyIleThrArgProPheSerArgPro100105 110AlaValAlaSerGlnArgArgAlaTrpAlaThrValGlyLeuValTrp115120125AlaAlaAlaLeuAlaLeuGlyLeuLeuProLeu LeuGlyValGlyArg130135140TyrThrValGlnTyrProGlySerTrpCysPheLeuThrLeuGlyAla145150155 160GluSerGlyAspValAlaPheGlyLeuLeuPheSerGlyLeuSerVal165170175GlyLeuSerPheLeuLeuAsnThrVa lSerValAlaThrLeuHisHis180185190ValTyrHisGlyGlnGluAlaAlaGlnGlnArgProArgAspSerGlu195 200205ValGluMetMetAlaGlnLeuLeuGlyIleMetValValAlaSerVal210215220CysTrpLeuProLeuLeuValPheIleAlaG lnThrValLeuArgAsn225230235240ProProAlaMetSerProAlaGlyGlnLeuSerArgThrThrGluLys245 250255GluLeuLeuIleTyrLeuArgValAlaThrTrpAsnGlnIleLeuAsp260265270ProTrpValTyrIleLeu PheArgArgAlaValLeuArgArgLeuGln275280285ProArgLeuSerThrArgProArgSerLeuSerLeuGlnProGlnLeu290 295300ThrGlnArgSerGlyLeuGln305310(2) INFORMATION FOR SEQ ID NO:38:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 312 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:38:LysTyrPheValValIleIleTyrAlaLeuValPheLeuLeuSerLeu151015LeuGlyAsnSerLeuValMet LeuValIleLeuTyrSerArgGlyVal202530ArgSerValThrIleValTyrLeuLeuAsnIleAlaIleAlaAspLeu35 4045LeuPheAlaLeuThrLeuProIleTrpAlaAlaSerLysValAsnGly505560TrpIlePheGlyThrPheLeuCysLysT rpSerLeuLeuLysGluVal65707580AsnPheTyrSerGlyIleLeuLeuLeuAlaCysIleSerValAspArg85 9095TyrLeuAlaIleValArgAlaThrArgThrLeuThrGlnLysArgHis100105110LeuValLysPheIleCy sLeuSerIleTrpGlyLeuSerLeuLeuLeu115120125AlaLeuProValLeuLeuPheArgArgThrValTyrSerSerAsnVal130 135140SerProAlaCysTyrGluAspMetGlyAsnAsnTyrAlaAsnTrpArg145150155160MetLeuLeuProIleL euProGlnSerPheGlyPheIleValProLeu165170175LeuIleMetLeuTyrCysTyrGlyPheThrLeuArgThrLeuPheLys 180185190AlaIleMetGlyGlnLysHisArgAlaMetArgValIlePheAlaVal195200205ValLeuIlePhe LeuLeuCysTrpLeuProTyrAsnLeuValLeuIle210215220AlaAspThrLeuMetArgThrGlnValIleGlnGluThrCysGluArg225 230235240ArgAsnHisIleAspArgAlaIleAspAlaThrGluIleLeuGlyIle245250255LeuHis SerCysLeuAsnProLeuIleTyrAlaPheIleGlyGlnLys260265270PheArgHisGlyLeuLeuLysIleLeuAlaIleHisGlyLeuIleSer 275280285LysAspSerLeuProLysAspSerArgProSerPheValGlySerSer290295300SerGlyHisTh rSerThrThrLeu305310(2) INFORMATION FOR SEQ ID NO:39:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 326 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:39:LeuPheP roIleValTyrSerIleIlePheValLeuGlyIleIleAla151015AsnGlyTyrValLeuTrpValPheAlaArgLeuTyrProSerLysLys 202530AsnGluIleLysIlePheMetValAsnLeuThrValAlaAspLeuLeu354045PheLeu IleThrLeuProLeuTrpIleValTyrTyrSerAsnGlnGly505560AsnTrpPheLeuProLysPheLeuCysAsnLeuAlaGlyCysLeuPhe65 707580PheIleAsnThrTyrCysSerValAlaPheLeuGlyValIleThrTyr859095A snArgPheGlnAlaValLysTyrProIleLysThrAlaGlnAlaThr100105110ThrArgLysArgGlyIleAlaLeuSerLeuValIleTrpValAlaIle 115120125ValAlaAlaAlaSerTyrPheLeuValMetMetAspSerThrAsnVal130135140ValSer AsnLysAlaGlySerGlyAsnIleThrArgCysPheGluArg145150155160TyrGluLysGlySerLysProValLeuIleIleHisIleCysIleVal 165170175LeuGlyPhePheIleValPheLeuLeuIleLeuPheCysAsnLeuVal180185190IleIleHisThrLeuLeuArgGlyProValLysGlnGlnArgAsnAla195200205GluValArgArgArgAlaLeuTrpMetValCysThrValIleAla Val210215220PheValIleCysPheValProHisHisMetValGlnLeuProTrpThr22523023524 0LeuAlaGluLeuGlyMetTrpProSerSerAsnHisGlnAlaIleAsn245250255AspAlaHisGlnValThrLeuCysLeuLeuSerThrAsn CysValLeu260265270AspProValIleTyrCysPheLeuThrLysLysPheArgLysHisLeu275280 285SerGluLysLeuAsnIleMetArgSerSerGlnLysCysSerArgVal290295300ThrArgAspThrGlyThrGluMetAlaIleProIleAsnHisTh rPro305310315320ValAsnProIleLysAsn325(2) INFORMATION FOR SEQ ID NO:40:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 333 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:40:TyrIleAsnThrIleValSerCysLeuValPheValLeuGlyIleIle1510 15GlyAsnSerThrLeuLeuArgIleIleTyrLysAsnLysCysMetArg202530AsnGlyProAsnIleLeuIleAlaSerIleAlaLeuGl yAspLeuLeu354045HisIleIleIleAspIleProIleMetAlaTyrLysLeuIleAlaGly505560 AspTrpProPheAlaCysLysLeuPheProPheLeuGlnLysSerSer65707580ValGlyIleThrValLeuAsnLeuCysAlaLeuSerVal AspArgTyr859095ArgAlaValAlaSerTrpSerArgValGlnGlyIleGlyIleProLeu100105 110ValThrAlaIleGluIleValSerIleTrpIleLeuSerPheIleLeu115120125AlaIleProGluAlaIleGlyPheTrpMetValPro PheGluTyrLys130135140GlyAlaGlnHisArgThrCysMetLeuAsnAlaThrSerLysLeuPhe145150155 160TyrGlnAspValLysAspTrpTrpLeuPheGlyPheTyrPheLeuLeu165170175ValCysThrAlaIlePheTyrThrLeuMet ThrCysGluMetLeuAsn180185190ArgArgAsnGlySerLeuArgIleAlaLeuSerGluHisLeuLysGln195200 205ArgArgGluValAlaLysThrValPheCysLeuValValIlePheAla210215220LeuCysTrpPheProLeuHisLeuSerArgIleLe uLysLysThrVal225230235240TyrAspGluMetAspThrAsnArgCysGluLeuLeuSerPheLeuLeu245 250255LeuMetTyrIleGlyIleAsnThrAlaThrMetSerCysIleAsnPro260265270IleAlaLeuTyrPheValSerL ysLysPheLysAsnCysPheGlnSer275280285CysLeuCysCysCysCysTyrGlnSerLysSerIleMetThrSerVal290295 300ProMetGlnGlyThrSerIleGlnTrpLysAsnHisGluGlnAsnAsn305310315320HisAsnThrGluArgSerSer HisLysAspSerIleAsn325330(2) INFORMATION FOR SEQ ID NO:41:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 350 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:41:LeuIleAlaSerProTrpPheAlaAlaSerPheCysValValGlyLeu151015AlaSerAsnLeuLeuAlaLeuSerValLeuAlaGlyA laArgGlnSer202530SerSerHisThrArgSerSerPheLeuThrPheLeuCysGlyLeuVal3540 45LeuThrLeuAspPheLeuGlyLeuLeuValThrGlyThrIleValVal505560SerGlnHisAlaAlaLeuPheGluTrpHisAlaValAspProGly Cys65707580ArgLeuCysArgLeuValProPheIleGlnLysAlaSerValGlyIle8590 95ThrValLeuSerLeuCysAlaLeuSerIleAspArgTyrArgAlaVal100105110AlaSerTrpSerArgIleLysGlyIleGlyVal ProLysTrpThrAla115120125ValGluIleValLeuIleTrpValValSerValValLeuAlaValPro130135 140GluAlaIleGlyPheAspThrThrSerAspTyrLysGlyLysProLeu145150155160ArgValCysMetLeuAsnProPheGlnLysThr AlaPheMetPheTyr165170175LysThrAlaAlaLysAspTrpTrpLeuPheAlaPheTyrPheCysLeu1801 85190ProLeuAlaIleThrAlaIlePheTyrThrLeuMetThrCysGluMet195200205LeuArgLysLysSerGlyMetGlnIleAl aLeuAsnAspHisLeuLys210215220GlnArgArgGluValAlaLysThrValPheCysLeuValLeuValPhe225230 235240AlaLeuCysTrpLeuProLeuHisLeuSerArgIleLeuLysLeuThr245250255LeuTyrAspGlnSerAsnProG lnArgCysGluLeuLeuSerPheLeu260265270LeuValLeuAspTyrIleGlyIleAsnMetAlaSerIleAsnSerCys275 280285IleAsnProIleAlaLeuTyrLeuValSerLysArgPheLysAsnCys290295300PheLysSerCysLeuCysCysTrpCys GlnThrPheGluGluLysGln305310315320SerLeuGluGluLysGlnSerCysLeuLysPheLysAlaAsnAspHis325 330335GlyTyrAspAsnPheArgSerSerAsnLysTyrSerSerSer340345350(2) INFORMATION FOR SEQ ID NO:42:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 328 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:42:IleTyrValIleProAlaValTyrGlyLeuIleIleValIleGlyLeu15 1015IleGlyAsnIleThrLeuIleLysIlePheCysThrValLysSerLeu202530AsnLeuPheIleSerS erIleAlaLeuGlyAspLeuLeuLeuLeuVal354045ThrIleCysAlaProValAspAlaSerLysTyrIleAlaAspArgTrp50 5560LeuPheGlyArgIleGlyCysLysLeuIleProPheIleGlnLeuThr65707580SerValGlyValSerVal PheThrLeuThrAlaLeuSerAlaAspArg859095TyrLysAlaIleValArgProThrCysIleGlnAlaSerLeuIleCys10 0105110LeuLysAlaAlaLeuIleTrpIleValSerLeuLeuAlaIleProGlu115120125AlaValPheSerAsp LeuHisProPheHisValLysAspThrAsnGln130135140ThrPheIleSerCysAlaProTyrProHisSerAsnGluLeuHisPro1451 50155160LysIleHisSerMetAlaSerPheLeuValPheTyrValIleProLeu165170175AlaIleIl eSerValTyrTyrTyrPheIleAlaArgAsnLeuIleGln180185190SerAlaTyrAsnLeuProValGluGlyAsnIleHisValLysLysGln 195200205IleGluSerArgLysArgLeuAlaLysThrValLeuValPheValGly210215220LeuPheAlaPheC ysTrpLeuProAsnHisValIleTyrLeuTyrArg225230235240SerTyrHisTyrSerGluValAspThrSerMetLeuHisPheValThr 245250255SerIleCysAlaArgLeuLeuAlaProThrAsnSerCysValAsnPro260265270 PheAlaLeuTyrLeuLeuSerLysSerPheArgGlnPheAsnThrGln275280285LeuLeuCysCysGlnProGlyLeuSerHisSerThrGlyArgSerLeu 290295300SerPheLysSerThrAsnProSerAlaThrPheSerLeuIleAsnArg305310315320 AsnIleCysHisGluGlyTyrVal325(2) INFORMATION FOR SEQ ID NO:43:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 345 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:43: CysValIleProSerSerLeuTyrLeuIleIleIleSerValGlyLeu151015LeuGlyAsnIleMetLeuValLysIlePheLeuThrAsnSerThr Met202530ArgSerValProAsnIlePheIleSerAsnIleAlaAlaGlyAspLeu354045 LeuLeuLeuLeuThrCysValProValAspAlaSerArgTyrPhePhe505560AspGluTrpValPheGlyLysLeuIleGlyCysLysLeuIleProAla 65707580IleGlnLeuThrSerValGlyValSerValProThrLeuThrAlaLeu85909 5SerAlaAspArgTyrArgAlaIleValAsnProMetAspMetThrSer100105110GlyValValLeuTrpThrSerValAlaValGlyIleTrpVal ValSer115120125ValLeuLeuAlaValProGluAlaValPheSerGluValAlaArgIle130135140 GlySerSerAspAsnSerSerPheThrAlaCysIleProTyrProGln145150155160ThrAspGluLeuHisProLysIleHisSerValLeuIlePh eLeuVal165170175TyrPheLeuIleProLeuValIleIleSerIleTyrTyrTyrHisIle180185 190AlaLysThrLeuIleArgSerAlaHisAsnLeuProGlyGluTyrAsn195200205GluHisThrLysLysGlnMetGluThrArgLysArgL euAlaLysIle210215220ValLeuValPheValGlyCysPheValPheCysTrpPheProAsnHis225230235 240IleLeuTyrLeuTyrArgSerPheAsnTyrLysGluIleAspProSer245250255LeuGlyThrCysValThrLeuValAlaArg ValLeuSerPheSerAsn260265270SerCysValAsnProPheAlaLeuTyrLeuLeuSerGluSerPheArg275280 285LysHisPheSerAsnGlnLeuCysCysGlyGlnLysSerTyrProGlu290295300ArgSerThrSerTyrLeuLeuSerSerSerAlaVal TrpArgSerLeu305310315320LysSerAsnAlaLysAsnValValThrAsnSerValLeuIleAsnGly325 330335HisSerThrLysGlnGluIleAlaLeu340345(2) INFORMATION FOR SEQ ID NO:44:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 316 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single (D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:44:TyrThrLeuSerPheIleTyrIlePheIlePheValIleCysGlxLeu151015LeuAl aAsnSerValValValTrpValAsnIleGlnAlaLysThrThr202530GlyTyrAspThrHisCysTyrIleLeuAsnLeuAlaIleAlaAspLeu 354045TrpTrpLeuThrIleProValTrpTrpSerLeuValGlnHisAsnGln505560TrpProMetGly GluLeuThrCysLysValThrHisLeuIlePheSer65707580IleAsnLeuPheSerGlyIlePhePheLeuThrCysMetSerValAsp 859095ArgTyrLeuSerIleThrTyrPheThrAsnThrProSerSerArgLys100105110L ysMetValArgArgAlaValCysIleLeuValTrpLeuLeuAlaPhe115120125CysValSerLeuProAspThrTyrTyrLeuLysThrValThrSerAla 130135140SerAsnAsnGluThrTyrCysArgSerPheTyrProGluHisSerIle145150155160 LysGluTrpLeuIleSerLeuLeuValSerValValLeuIleGlyPhe165170175AlaValProPheSerIleIleAlaValPheTyrPheSerLeuIleA la180185190ArgAlaIleSerAlaSerSerAspGlnGluLysHisSerSerArgLys195200205 IleIlePheSerTyrValValValPheLeuValCysTrpLeuProTyr210215220HisValAlaValLeuLeuAspIlePheSerIleLeuHisTyrIlePro 225230235240PheThrCysArgLeuGluHisAlaLeuPheThrAlaLeuHisValThr245250 255GlnCysLeuSerLeuValHisCysCysValAsnProValLeuTyrSer260265270PheIleAsnArgAsnTyrArgTyrGluIleAsnTrpIle PheLysTyr275280285SerAlaLysThrGlyLeuThrLysLeuIleAspAlaSerArgValSer290295300GlxThrGluTyrSerAlaLeuGluGlnAsnAlaLys305310315(2) INFORMATION FOR SEQ ID NO:45:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 353 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single (D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:45:LysValLeuValThrAlaIleTyrLeuAlaLeuPheValValGlyThr151015ValGlyAsnSe rValThrAlaPheThrLeuAlaArgLysLysSerLeu202530GlnSerLeuGlnSerThrValHisTyrHisLeuSerSerLeuAlaLeu3 54045SerAspLeuLeuIleLeuLeuTrpValGluLeuTyrAsnPheIleTrp505560HisHisProTrpAlaPhe GlyAspAlaGlyCysArgGlyTyrTyrPhe65707580LeuArgAspAlaCysThrTyrAlaThrAlaLeuAsnValAlaSerLeu 859095SerValGluArgTyrLeuAlaIleCysHisProPheLysAlaLysThr100105110LeuMetS erArgSerArgThrLysLysPheIleSerAlaIleTrpLeu115120125AlaSerAlaLeuLeuAlaIleProMetLeuPheThrLeuGlyLeuGln130 135140AsnArgSerGlyAspGlyThrHisProGlyGlyLeuValCysThrPro145150155160IleVal AspThrAlaThrValLysValValIleGlnValAsnThrPhe165170175MetSerPheLeuPheProMetLeuValIleSerIleLeuAsnThrVal 180185190IleAlaAsnLysLeuThrValMetValHisGlnAlaAlaGluGlnGly195200205Arg ValCysThrValGlyThrHisAsnGlyLeuGluHisSerThrPhe210215220AsnMetArgIleGluProGlyArgValGlnAlaLeuArgHisGlyVal225 230235240LeuValLeuArgAlaValValIleAlaPheValValCysTrpLeuPro245250255 TyrLeuCysTyrIleSerAspGluGlnTrpArgThrPheLeuPheAsp260265270PheTyrHisTyrPheTyrMetLeuThrAsnAlaLeuPheTyrVal Ser275280285SerAlaIleAsnProIleLeuTyrAsnLeuValSerAlaAsnPheArg290295300G lnValPheLeuSerThrLeuAlaCysLeuPheCysProGlyTrpPro305310315320LeuIleArgArgLysLysArgProThrPheSerArgLysProAs nSer325330335MetSerSerAsnHisAlaPheSerThrSerAlaThrArgPheThrLeu340345 350Tyr(2) INFORMATION FOR SEQ ID NO:46:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 316 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:46:AlaIleGlnAlaProPheLeuTrpValLe uPheLeuLeuAlaAlaLeu151015GluAsnIlePheValLeuSerValPheCysLeuHisLysThrAsnCys20 2530ThrValAlaGluIleTyrLeuGlyAsnIleAlaSerAlaAspLeuIle354045IleAlaCysGlyLeuProPheTrpAla IleThrIleAlaAsnAsnPhe505560AspTrpLeuPheGlyGluValLeuCysArgValValAsnLeuTyrMet6570 7580AsnLeuTyrSerSerIleCysPheLeuValSerIleAspArgTyrLeu859095AlaLeuValLysThrMetSerAs nLeuArgTrpAlaLysLeuTyrSer100105110LeuValIleTrpSerCysThrLeuLeuLeuSerSerProMetLeuVal115 120125PheArgThrMetTyrArgGluGluGlyHisAsnValThrCysValIle130135140ValTyrProSerArgSerTrpGluValP heLeuLeuAsnLeuValGly145150155160PheLeuLeuProLeuSerIleIleThrPheCysThrValArgIleMet165 170175ValLeuArgAsnAsnGluMetLysLysPheLysGluValGlnThrGlu180185190LysLysAlaThrVal LeuValIleAlaValLeuGlyLeuPheValLeu195200205CysTrpPheProPheGlnIleSerThrPheLeuAspThrLeuLeuArg210 215220LeuGlyValLeuSerGlyCysTrpAsnGluArgAlaValAspIleVal225230235240ArgGlnIleSerSer TyrValAlaTyrSerAsnSerCysLeuAsnPro245250255LeuValTyrValIleValGlyLysArgPheArgLysLysSerArgGlu 260265270ValTyrGlnAlaIleCysArgLysGlyGlyCysMetGlyGluSerVal275280285LeuAsnSerMe tGlyThrLeuArgThrSerIleSerValAspArgGln290295300IleHisLysLeuGlnAspTrpAlaGlyAsnLysGln305310 315(2) INFORMATION FOR SEQ ID NO:47:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 347 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:47:IleLeuLeuValValIleIleCysGlyLeuGlyIl eValGlyAsnIle151015MetValValLeuValValMetArgThrThrProThrAsnCysTyrLeu2025 30ValSerIleAlaValAlaAspLeuMetValLeuValAlaAlaGlyLeu354045ProAsnIleThrAspSerIleTyrGlySerTrp ValTyrGlyTyrVal505560GlyCysLeuCysIleThrTyrLeuGlnTyrLeuGlyIleAsnAlaSer657075 80SerCysSerIleThrAlaPheThrIleGluArgTyrIleAlaIleCys859095HisProIleLysAlaGlnPheLeuCysTh rPheSerArgAlaLysLys100105110IleIleIlePheValTrpAlaPheThrSerIleTyrLeuPheLeuLeu115120 125AspIleAsnIleSerThrTyrLysAsnAlaValValValSerCysGly130135140TyrLysIleSerArgAsnTyrTyrSerProIleT yrLeuMetAspPhe145150155160GlyValPheTyrValValProLeuIleAlaThrValLeuTyrGlyPhe165 170175IleAlaArgIleLeuPheLeuAsnProIleProSerAspProLysGlu180185190AsnSerLysMetTrpLysAsn AspSerIleHisGlnAsnLysAsnLeu195200205AsnLeuAsnAlaSerSerArgLysGlnValThrIleAsnLeuAlaVal21021 5220ValValIleLeuPheAlaLeuLeuTrpAsnThrTyrArgThrLeuVal225230235240ValValAsnSerPheLeuSer SerProPheGlnGluAsnTrpLysLeu245250255LeuLysCysArgIleCysIleTyrLeuAsnSerAlaIleAsnProVal260 265270IleTyrAsnIleMetSerGlnLysArgPheAlaAlaPheArgLysLeu275280285CysAsnCysLysGlnLy sProThrGluLysAlaAlaAsnTyrSerVal290295300AlaLeuAsnTyrSerValIleLysGluSerAspArgPheSerThrGlu305310 315320LeuGluAspIleThrValThrAspThrTyrValSerThrThrLysVal325330335SerPheAspA spThrCysIleAlaSerGluAsn340345(2) INFORMATION FOR SEQ ID NO:48:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 341 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(x i) SEQUENCE DESCRIPTION: SEQ ID NO:48:LeuAlaLeuTrpAlaThrAlaTyrLeuAlaLeuValLeuValAlaVal151015ThrGlyAsnAlaIleValIleTrpIleIleLeuAl aHisArgArgMet202530ArgThrValThrAsnTyrPheIleValAsnIleAlaLeuAlaAspLeu3540 45LeuAsnAlaAlaPheAsnPheValTyrAlaSerHisAsnIleTrpTyr505560PheGlyArgAlaPheCysTyrPheGlnAsnLeuPheProIle ThrAla65707580MetPheValSerIleTyrSerMetThrAlaIleAlaAlaAspArgTyr8590 95MetAlaIleValHisProPheGlnProArgLeuSerAlaProSerThr100105110LysAlaValIleAlaGlyIleTrpLeuValA laIleLysLeuAlaPhe115120125ProGlnCysPheTyrSerThrValThrMetGlnGlyAlaThrLysCys130135 140ValValAlaTrpProGluAspSerGlyGlyLysThrLeuLeuLeuTyr145150155160HisLeuValValIleAlaLeuIleTyrPhe LeuProIleAlaLeuAla165170175TyrSerValIleGlyLeuThrLeuTrpArgArgAlaValProGlyHis180 185190GlnAlaHisGlyAlaAsnLeuArgHisLeuGlnAlaLysLysLysPhe195200205ValLysThrMetValLeuValValVal ThrPheAlaIleCysTrpLeu210215220ProTyrHisLeuTyrPheIleLeuGlySerPheGlnGluAspIleTyr225230 235240CysHisLysPheIleGlnGlnValTyrLeuAlaLeuPheTrpLeuAla245250255MetSerSerThrMetTyrAs nProIleIleTyrCysCysLeuAsnHis260265270ArgPheArgSerGlyPheArgLeuAlaPheArgCysCysProTrpVal275 280285ThrProThrLysGluAspLysLeuGluLeuThrProThrThrSerLeu290295300SerThrArgValAsnArgCysHisT hrLysGluThrLeuPheMetAla305310315320GlyAspThrAlaProSerGluAlaThrSerGlyGluAlaGlyArgPro325 330335GlnAspGlySerGly340(2) INFORMATION FOR SEQ ID NO:49:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 340 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:49:IleValLeuTrpAlaAlaAlaTyrThrValIleValValArgSerVal151015ValGlyAsnValValValIle TrpIleIleLeuAlaHisLysArgMet202530ArgThrValThrAsnTyrPheLeuValAsnIleAlaPheAlaPheAla35 4045LeuAsnThrTrpAsnPheThrTyrAlaValHisAsnValTrpTyrTyr505560GlyLeuPheTyrCysLysPheHisAsnPh ePheProIleAlaAlaLeu65707580PheAlaSerIleTyrSerMetThrAlaValAlaPheAspArgTyrLeu85 9095IleIleHisProLeuGlnProArgLeuSerAlaThrAlaThrLysVal100105110ValIlePheValIleTrp ValIleAlaLeuLeuLeuAlaSerProGln115120125GlyTyrTyrSerThrThrGluLeuSerArgValValCysMetIleGlu130 135140TrpProGluHisProAsnArgThrTyrGluLysAlaTyrHisIleCys145150155160ValThrValLeuIleTy rPheLeuProLeuLeuValIleGlyTyrAla165170175TyrThrValValGlyIleThrLeuTrpAlaSerGluIleProGlyAsp 180185190SerSerAspArgTyrHisGluGlnValSerAlaLysArgLysValVal195200205LysMetIleCysV alValValCysThrPheAlaIleCysTrpLeuPro210215220PheHisValPhePheLeuLeuProTyrIleAsnProAspLeuTyrLeu225 230235240LysLysPheIleGlnGlnValTyrIleAlaSerMetTrpLeuAlaMet245250255SerSer ThrMetTyrAsnProIleIleTyrCysCysLeuAsnAspArg260265270PheArgLeuGlyPheLysHisAlaPheArgCysCysProPheIleSer 275280285AlaGlyAspTyrGluGlyLeuGluMetIleLysSerThrArgTyrLeu290295300GlnThrLeuSer SerValTyrLysValSerArgLeuGluThrThrIle305310315320SerThrValValGlyAlaHisGluGluGluProGluGluGlyProLys 325330335AlaThrProSer340(2) INFORMATION FOR SEQ ID NO:50:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 336 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single (D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:50:IleAlaLeuTrpSerLeuAlaTyrGlyLeuValValAlaValAlaVal151015PheGlyAsnLe uIleValIleTrpIleIleLeuAlaHisLysArgMet202530ArgThrValThrAsnTyrPheLeuValAsnLeuAlaPheSerAspAla3 54045SerValAlaAlaPheAsnThrLeuIleAsnPheIleTyrGlyLeuHis505560SerGluTrpTyrPheGly AlaAsnTyrCysArgPheGlnAsnPhePhe65707580ProIleThrAlaValPheAlaSerIleTyrSerMetAlaIleAlaVal 859095AspArgTyrMetAlaIleIleAspProLeuLysProArgLeuSerAla100105110ThrAlaT hrLysIleValIleGlySerIleTrpIleLeuAlaPheLeu115120125LeuAlaPheProGlnCysLeuTyrSerLysIleLeuGlyArgThrLeu130 135140CysTyrValTrpProGluGlyProLysGlnHisPheThrTyrHisIle145150155160IleVal IleIleLeuValTyrCysPheProLeuLeuIleLeuThrTyr165170175ThrIleValGlyIleThrLeuTrpGlyGlyGluIleProGlyAspThr 180185190CysAspLysTyrHisGluGlnLeuLysAlaLysArgLysValValMet195200205Asn IleValValValThrPheAlaIleCysTrpLeuProTyrHisVal210215220TyrPheIleLeuThrAlaIleTyrGlnGlnLeuAsnArgTrpLysTyr225 230235240IleGlnGlnValTyrLeuAlaSerPheTrpLeuAlaMetSerSerThr245250255 MetTyrAsnProIleIleTyrCysCysLeuAsnLysArgPheArgAla260265270GlyPheLysArgAlaPheArgTrpCysProPheIleGlnValSer Ser275280285TyrAspGluLeuGluLeuLysThrThrArgPheHisProThrArgGln290295300S erSerLeuTyrThrValSerPheMetSerValThrValLeuPheAsp305310315320ProAsnAspGlyAspProThrLysSerSerArgLysLysArgAl aVal325330335(2) INFORMATION FOR SEQ ID NO:51:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 325 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi ) SEQUENCE DESCRIPTION: SEQ ID NO:51:MetIleProThrLeuTyrSerIleIlePheValValGlyIlePheGly151015AsnSerLeuValValIleValIleTyrPheTyrMet LysLeuLysThr202530TyrAlaSerValPheLeuLeuAsnLeuAlaLeuAlaAspLeuCysPhe3540 45LeuLeuThrLeuProLeuTrpAlaValTyrThrLeuTyrArgTrpPro505560PheGlyAsnTyrLeuCysLysIleAlaSerAlaSerValSerP heAsn65707580LeuTyrAlaSerValPheLeuLeuThrCysLeuSerIleAspArgTyr8590 95LeuAlaIleValHisProMetLysSerArgLeuArgArgLeuValAla100105110LysValThrCysIleIleIleTrpLeuLeuAl aGlyIleAlaSerLeu115120125ProThrIleIleHisArgAsnPhePheIleGluAsnThrAsnIleThr130135 140ValCysAlaPheHisTyrGluSerGlnAsnSerThrLeuProValGly145150155160LeuGlyLeuThrLysAsnIleLeuGlyPheL euPheProPheLeuIle165170175IleLeuThrSerTyrThrLeuIleTrpLysThrLeuLysLysAlaTyr180 185190GluIleGlnLysAsnLysProArgLysAspAspIlePheLysIleIle195200205IleAlaIleValLeuPhePhePhePhe SerTrpValProHisAsnIle210215220PheThrPheMetValLeuIleGlnLeuGlyLeuIleArgAspCysLys225230 235240IleGluAspIleValAspThrAlaMetProIleThrIleCysLeuAla245250255TyrPheGlnGlnAsnLeuAsn ProLeuPheTyrGlyPheLeuGlyLys260265270LysPheLysLysTyrPheLeuHisAlaLeuLeuLysTyrIleProPro275 280285LysAlaLysSerHisSerAsnLeuSerThrLysMetSerThrLeuSer290295300TyrArgProSerGluGlnGlyAsnSe rSerThrLysLysProAlaPro305310315320CysIleGluValGlu325(2) INFORMATION FOR SEQ ID NO:52:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 282 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:52:IleValHisTrpValIleMetSerIleSerProValGlyPheValGlu15 1015AsnGlyIleLeuLeuTrpPheLeuCysPhePheThrValTyrThrHis202530LeuSerIleAlaAspIleSerLe uLeuPheCysIlePheIleLeuSer354045IleAspTyrAlaLeuAspTyrGluLeuSerSerGlyHisTyrTyrThr5055 60IleValThrLeuSerValThrPheLeuPheGlyTyrAsnThrGlyLeu65707580TyrLeuLeuThrAlaIleSerVal GluArgCysLeuSerValLeuTyr859095ProIleTrpTyrArgCysHisArgProLysTyrGlnSerAlaLeuVal100 105110CysAlaLeuLeuTrpAlaLeuSerCysLeuValThrThrMetTyrVal115120125MetCysIleAspArgPheGlu GluSerHisSerArgAsnAspCysArg130135140AlaValIleIlePheIleAlaIleLeuSerPheLeuValPheThrPro145150 155160SerValSerSerThrIleLeuValValLysIleArgLysAsnThrTrp165170175AlaSerHisSerSer LysLeuTyrIleValIleMetValThrIleIle180185190IlePheLeuIlePheAlaMetProMetArgLeuLeuTyrLeuLeuTyr195 200205TyrGluTyrTrpSerThrPheGlyAsnLeuHisHisIleSerLeuLeu210215220PheSerThrIleAsnSerSe rAlaAsnProPheIleTyrPhePheVal225230235240GlySerSerLysLysLysArgPheLysGluSerLeuLysValValLeu 245250255ThrArgAlaPheLysAspGluMetGlnProArgArgGlnLysAspAsn260265270CysAsnT hrValThrValGluThrValVal275280(2) INFORMATION FOR SEQ ID NO:53:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 332 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:53:TyrAspPheLeuArgValLeuIleTrpLeuIleAsnIleLeuAlaIle151015MetGlyAsnValMetThrLeuPheValLeuLeuThrSe rArgTyrLys202530LeuThrValProArgPheIleMetAsnLeuSerPheAlaAspPheCys3540 45MetLeuTyrLeuLeuLeuIleAlaSerValAspSerGlnThrLysGly505560GlnTyrTyrAsnHisAlaIleAspTrpGlnThrGlySerGlyCys Ser65707580ThrAlaGlyPhePheThrValLeuAlaSerGluLeuSerValTyrThr8590 95LeuThrValIleThrLeuGluArgTrpHisThrIleThrTyrAlaIle100105110HisIleAspGlnLysLeuArgLeuArgHisAlaI leLeuIleMetLeu115120125GlyGlyTrpLeuPheSerSerLeuIleAlaMetLeuProLeuValCys130135 140ValSerAsnTyrMetLysValSerIleCysLeuProMetValGluThr145150155160ThrLeuSerGlnValTyrIleLeuThrIleLeu IleLeuAsnValVal165170175AlaPheLeuIleIleCysAlaCysTyrIleLysIleTyrPheAlaVal18018 5190ArgAsnProGluIleMetAlaThrAsnLysAspThrLysIleAlaLeu195200205AlaIleLeuIlePheThrAspPheThrCys MetProIleSerPhePhe210215220AlaIleSerAlaAlaPheLysValProLeuIleValThrAsnSerLys2252302 35240ValLeuLeuValLeuPheTyrProIleAsnSerCysAlaAsnProPhe245250255LeuTyrAlaIlePheThrLysTh rPheGlnArgAspPhePheIleLeu260265270SerLysPheCysCysLysArgArgAlaAspIleTyrArgArgLysAsp275 280285PheSerAlaTyrThrSerAsnCysLysLysGlyPheThrGlySerAsn290295300LysProSerGlnSerThrLeuLysLeuS erThrLeuHisCysGlnGly305310315320ThrAlaLeuLeuAspLysArgArgTyrThrGluCys325330(2) INFORMATION FOR SEQ ID NO:54:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 336 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:54:TyrLysPheLeuArgIleValValTrpPheValSerLeuLeuA laLeu151015LeuGlyAsnValPheValLeuLeuIleLeuLeuThrSerHisTyrLys2025 30LeuAsnValProArgPheIleMetAsnIleAlaPheAlaAspPheCys354045MetMetTyrLeuLeuLeuIleAlaSerValAspLeuTyrThr HisSer505560GluTyrTyrAsnHisAlaIleAspTrpGlnThrGlyProGlyCysAsn657075 80ThrAlaGlyPhePheThrValPheAlaSerGluLeuSerValTyrThr859095LeuThrValIleThrLeuGluArgTrpTyrAlaIleT hrPheAlaMet100105110ArgLeuAspArgLysIleArgLeuArgHisAlaCysAlaIleMetVal115120 125GlyGlyTrpValCysCysPheLeuLeuAlaLeuLeuProLeuValGly130135140IleSerSerTyrAlaLysValSerIleCysLeuProMetThr GluThr145150155160ProLeuAlaLeuAlaTyrIleValPheValLeuThrLeuAsnIleVal165170 175AlaPheValIleValCysCysCysTyrValLysIleTyrIleThrVal180185190ArgAsnProGlnTyrAsnProGlyAspLys AspThrLysIleAlaLys195200205ArgMetAlaValLeuIlePheThrAspPheIleCysMetAlaProIle210215 220SerPheTyrAlaLeuSerAlaIleLeuAsnLysProLeuIleThrVal225230235240SerAsnSerLysIleLeuLeuValLeuPh eTyrProLeuAsnSerCys245250255AlaAsnProPheLeuTyrAlaIlePheThrLysAlaPheGlnArgAsp260 265270ValPheIleLeuLeuSerLysPheGlyIleCysLysArgGlnAlaGln275280285AlaTyrArgGlyGlnArgValProP roLysAsnSerThrAspIleGln290295300ValGlnLysValThrHisAspMetArgGlnGlyAlaLeuAsnMetGlu305310 315320AspValValGluLeuIleGluAsnSerHisLeuThrProLysLysGln325330335(2) INFORMATION FOR SEQ ID NO:55:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 327 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:55:TyrAsnIleLeuArgValLeuIleTrpPheIleSerIleLeuAlaIle15 1015ThrGlyAsnIleIleValLeuValIleLeuThrThrSerGlnTyrLys202530LeuThrValProAr gPheLeuMetAsnIleAlaPheAlaAspLeuCys354045IleGlyIleTyrLeuLeuLeuIleAlaSerValAspIleHisThrLys50 5560SerGlnTyrHisAsnTyrAlaIleAspTrpGlnArgGlyAlaGlyCys65707580AspAlaAlaGlyPhe PheThrValPheAlaSerGluLeuSerValTyr859095ThrLeuThrAlaIleThrLeuGluArgTrpHisThrIleThrHisIle 100105110MetGlnIleAspCysLysValGlnLeuArgHisAlaAlaSerValMet115120125ValMetGlyTrp IlePheAlaPheAlaAlaAlaLeuPheProIlePhe130135140GlyIleSerSerTyrMetLysValSerIleCysLeuProLeuIleAsp145 150155160SerProLeuSerGlnLeuTyrValMetSerLeuLeuValLeuAsnVal165170175LeuAla PheValValIleCysGlyCysTyrThrHisIleTyrLeuThr180185190ValArgAsnProAsnIleValSerSerSerSerAspThrArgIleAla 195200205LysArgMetLeuIlePheThrAspPheLeuLeuProIleSerPhePhe210215220AlaIleSerAl aSerLeuLysValProLeuIleThrValSerLysAla225230235240LysIleLeuLeuValLeuPheHisProIleAsnSerCysAlaAsnPro 245250255PheLeuTyrAlaIlePheThrLysAsnPheArgArgAspPhePheIle260265270 LeuLeuSerLysCysGlyCysTyrGluMetGlnAlaGlnIleTyrArg275280285ThrGluThrSerSerThrValHisAsnThrHisProArgAsnGlyHis 290295300CysSerSerAlaProArgValThrSerGlySerSerArgTyrIleLeu305310315320 ValProLeuSerLeuGlnAsn325(2) INFORMATION FOR SEQ ID NO:56:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 309 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:56: SerMetLeuAlaAlaTyrMetPheLeuLeuIleValLeuGlyPhePro151015IleAsnPheLeuThrLeuTyrValThrValGlnHisLysLysLeuA rg202530ThrProIleAsnTyrIleLeuLeuAsnLeuAlaValAlaAspLeuPhe354045 MetValLeuGlyGlyPheThrSerThrLeuTyrThrSerLeuHisGly505560TyrPheValPheGlyProThrGlyCysAsnLeuGluGlyPhePheAla 65707580ThrLeuGlyGlyGluIleAlaLeuTrpSerLeuTrpLeuAlaIleGlu859095ArgTyrValValValCysLysProMetSerAsnPheArgPheGlyGlu100105110AsnHisAlaIleMetGlyValAlaPheThrTrpValMetAla LeuAla115120125CysAlaAlaProProIleAlaGlyTrpSerArgTyrIleProGluGly130135140 LeuGlnCysSerCysGlyIleAspTyrTyrThrLeuLysProGluVal145150155160AsnAsnGluSerPheValIleTyrMetPheValValHisPhe ThrIle165170175ProLeuIleIlePhePheCysTyrGlyGlnLeuValPheThrValLys180185 190GluAlaAlaAlaGlnGlnGlnGluSerAlaThrThrGlnLysAlaGlu195200205LysGluValThrArgMetValIleIleMetValIleAl aPheLeuIle210215220CysTrpValProTyrAlaSerValAlaPheTyrIlePheThrHisGln225230235 240GlySerAsnPheGlyProIlePheMetArgIleProAlaPhePheAla245250255LysSerAlaAlaIleTyrAsnProValIleT yrIleIlePheAsnLys260265270GlnPheArgAsnCysMetLeuGlnLeuIleCysCysGlyLysAsnPro275280 285LeuGlyAspAspGluAlaSerAlaThrValSerLysArgGluThrSer290295300GlnValAlaProAla305(2) INFORMATION FOR SEQ ID NO:57: (i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 297 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:57:MetIlePheValValIleAlaSerValPheThrAsnGlyLeuValLeu1 51015AlaAlaThrMetLysPheLysLysLeuProHisProIleAsnTrpIle202530Leu ValAsnLeuAlaValAlaAspIleAlaGlyThrValIleAlaSer354045ThrIleSerValValAsnGlnValTyrGlyTyrPheValLeuGlyHis 505560ProMetCysValLeuGluGlyTyrThrValSerLeuCysGlyIleThr65707580GlyL euTrpSerLeuAlaIleIleSerTrpGluArgTrpMetValVal859095CysLysProPheGlyAsnValArgPheAspAlaLysIleAlaIleVal 100105110GlyIleAlaPheSerTrpIleTrpAlaAlaValTrpThrAlaProPro115120125I lePheGlyTrpSerArgTyrTrpProHisGlyLeuLysThrSerCys130135140GlyProAspValPheSerGlySerSerTyrProGlyValGlnSerLeu145 150155160LeuCysIleThrProLeuSerIleIleValLeuCysTyrLeuGlnVal165170175TrpThrAlaIleArgAlaValAlaLysGlnGlnLysGluSerGluSer180185190ThrGlnLysAlaGluLysGluValThrArgMetTrpValMetV alLeu195200205AlaPheCysPheCysTrpGlyProTyrAlaPhePheAlaCysPheAla210215220 AlaAlaAsnProGlyTyrProPheHisProLeuMetAlaAlaLeuPro225230235240AlaPhePheAlaLysSerAlaThrIleTyrAsnProValIle TyrVal245250255PheMetAsnArgGlnPheArgAsnCysIleLeuGlnLeuPheGlyLys260265 270LysValAspAspGlySerGluLeuSerSerAlaSerLysThrGluVal275280285SerSerValSerSerValSerProAla290 295(2) INFORMATION FOR SEQ ID NO:58:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 297 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:58:ArgCysPheValValThrAlaSerValPh eThrAsnGlyLeuValLeu151015AlaAlaThrMetLysPheLysLysLeuArgHisProLeuAsnTrpIle20 2530LeuValAsnIleAlaValAlaAspIleAlaGlyThrValIleAlaSer354045ThrIleSerIleValAsnGlnValSer GlyTyrPheValLeuGlyHis505560ProMetCysValLeuGluGlyTyrThrValSerLeuCysGlyIleThr6570 7580GlyLeuTrpSerLeuAlaIleIleSerTrpGluArgTrpLeuTrpCys859095LysProPheGlyAsnValArgPh eAspAlaLysIleAlaIleValGly100105110IleAlaPheSerTrpIleTrpSerAlaValTrpThrAlaProProIle115 120125PheGlyTrpSerArgTyrTrpProHisGlyLeuLysThrSerCysGly130135140ProAspValPheSerGlySerSerTyrP roGlyValGlnSerLeuVal145150155160IleMetValThrCysCysIleIleProIleAlaIleIleLeuCysTyr165 170175LeuGlnValTrpLeuAlaIleArgAlaValAlaLysGlnGlnLysGlu180185190SerGluSerThrGln LysAlaGluLysGluValThrArgMetLeuPhe195200205AlaTyrCysValCysTrpGlyProTyrThrPhePheAlaCysPheAla210 215220AlaAlaAsnProGlyTyrAlaPheHisProLeuMetAlaAlaLeuPro225230235240AlaTyrPheAlaLys SerAlaThrIleTyrAsnProValIleTyrVal245250255PheMetAsnArgGlnPheArgAsnCysIleLeuGlnLeuPheGlyLys 260265270LysValAspAspGlySerGluLeuSerSerAlaSerLysThrGluVal275280285SerSerValSe rSerValSerProAla290295(2) INFORMATION FOR SEQ ID NO:59:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 305 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:59:G lnAlaAlaPheMetGlyThrValPheLeuIleGlyPheProLeuLeu151015ValAlaThrLeuAlaTyrLysLysLeuArgGlnProAsnTyrIleLeu202530ValAsnValSerPheGlyGlyPheLeuLeuCysIlePheSerValPhe354045 ProValPheValAlaSerCysAsnGlyTyrPheValPheGlyArgHis505560ValCysAlaLeuGluGlyPheLeuGlyThrValAlaGlyLeuValThr65 707580GlyTrpSerLeuAlaPheLeuAlaPheGluArgTyrIleValIleCys859095LysProPheGlyAsnPheArgPheSerSerLysHisAlaLeuThrVal100105110ValIleAlaThrTrpThrIleGlyIleGlyValSerIleProPr oPhe115120125PheGlyTrpSerArgPheIleProGluGlyLeuGlnCysSerCysGly130135140 ProAspLysTyrThrValGlyThrLysTyrArgSerGluSerTyrThr145150155160TrpPheLeuPheIlePheCysPheIleValProLeuSerLeuI leCys165170175PheSerTyrThrGlnLeuLeuArgAlaLeuLysAlaValAlaAlaGln180185 190GlnGlnGluSerAlaThrThrGlnLysAlaGluArgGluValSerArg195200205MetValValValMetValGlySerPheCysValCysTyr ValProTyr210215220AlaAlaPheAlaMetTyrMetValAsnAsnArgAsnHisGlyLeuAsp225230235 240LeuArgLeuValArgIleProSerPhePheSerLysSerAlaCysIle245250255TyrAsnProIleIleTyrCysPheMetAsnLys GlnPheGlnAlaCys260265270IleMetMetValCysGlyLysAlaMetMetGluSerAspThrCysSer275280 285SerGlnLysThrGluValSerThrValSerSerThrGlnValGlyPro290295300Asn305(2) INFORMATION FOR SEQ ID NO:60:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 293 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:60:LeuIleTyrGlyLeuPheLeuSerMetTyrLeuValThrValIleGly15 1015AsnIleSerIleIleValAlaIleIleSerAspProCysLeuHisThr202530ProMetTyrPhePheL euSerAsnLeuSerPheValAspIleCysPhe354045IleSerThrThrValProValAsnThrGlnThrGlnAsnAsnValIle50 5560ThrTyrAlaGlyCysIleThrGlnIleTyrPhePheLeuLeuPheVal65707580GluLeuAspAsnPheLeu LeuThrIleMetAlaTyrAspArgTyrVal859095AlaIleCysHisProMetHisTyrThrValIleMetAsnTyrLysLeu10 0105110CysGlyPheLeuValLeuValSerTrpIleValSerValLeuHisAla115120125LeuPheGlnSerLeu AlaLeuProPheCysThrHisLeuGluIlePro130135140HisTyrPheCysGluProAsnGlnValIleGlnLeuThrCysSerAsp1451 50155160AlaPheLeuAsnAspLeuValIleTyrPheThrLeuValLeuLeuAla165170175ThrValPr oIleAlaGlyIlePheTyrSerTyrPheAlaIleSerSer180185190ValHisGlyLysTyrLysAlaPheSerThrCysAlaSerHisLeuSer 195200205ValValSerLeuPheTyrCysThrGlyLeuGlyValTyrLeuSerSer210215220AlaAlaAsnAsnS erLeuSerAlaThrAlaSerValMetTyrThrVal225230235240ValThrProMetValAsnProPheIleTyrSerLeuArgAsnLysAsp 245250255ValLysSerValLeuLysLysThrLeuCysGluGluValIleArgSer260265270 ProProSerLeuLeuHisPhePheLeuValLeuCysHisLeuProCys275280285PheIlePheCysTyr290(2) INFORMATION FOR SEQ ID NO:61:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 284 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:61:LeuLeuPheLeuLeuPheLeuIleMetTyrLeuAlaThrValLeuGly15 1015AsnLeuLeuIleIleLeuAlaIleGlyGlyAspSerArgLeuHisThr202530ProMetTyrPhePhe LeuSerAsnLeuSerPheValAspValCysPhe354045SerSerThrThrValProLysValLeuAlaAsnHisIleLeuGlySer50 5560GlnAlaIleSerPheSerGlyCysLeuThrGlnLeuTyrPheLeuAla65707580ValPheGlyAsnMetAs pAsnPheLeuLeuAlaValMetSerTyrAsp859095ArgTyrValAlaIleCysHisProLeuHisTyrThrThrIleArgGln1 00105110LeuCysValLeuLeuValValGlySerTrpValValAlaAsnMetAsn115120125CysLeuLeuHisIl eLeuIleMetAlaArgLysSerPheCysAlaAsp130135140LeuProHisPhePheCysAspGlyThrProLeuLeuLysLeuSerCys145 150155160SerAspThrHisLeuAsnGluLeuMetIleLeuThrGluGlyAlaVal165170175ValMetV alThrProPheValCysIleLeuIleSerTyrIleHisIle180185190ThrCysAlaValLeuArgValSerSerProArgGlyGlyTrpLysSer 195200205PheSerThrCysGlySerHisIleAlaValValCysLeuPheTyrGly210215220ThrValIleAla ValTyrPheAsnProSerSerSerHisLeuAlaGly225230235240ArgAspMetAlaAlaAlaValMetTyrAlaValValThrProMetIle 245250255AsnProPheIleTyrSerLeuArgAsnSerAspMetLysAlaAlaLeu260265270 ArgLysValLeuAlaMetArgPheProSerLysGln275280(2) INFORMATION FOR SEQ ID NO:62:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 277 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii ) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:62:LeuLeuPheLeuLeuPheLeuValMetTyrLeuLeuThrValValGly151015AsnLeuAlaIleIleSerLeuVal GlyAlaHisArgCysLeuGlnPro202530HisThrProMetTyrPhePheLeuCysAsnLeuSerPheLeuGluIle35 4045TrpPheThrThrAlaCysValProLysThrLeuAlaThrPheAlaPro505560ArgGlyGlyValIleSerLeuAlaGlyCysAl aThrLysTyrPheVal65707580PheSerLeuGlyCysThrGluTyrPheLeuLeuAlaValMetAlaTyr85 9095AspArgTyrLeuAlaIleCysLeuProLeuArgTyrGlyGlyIleMet100105110ArgProGlyIleAlaMetArg LeuAlaLeuGlySerTrpLeuCysGly115120125PheSerAlaIleThrValProAlaThrLeuIleAlaArgLeuSerPhe1301 35140CysGlySerArgValIleAsnHisPhePheCysAspIleSerProTrp145150155160IleValLeuSerCysThrAs pThrGlnValValGluLeuValSerPhe165170175GlyIleAlaPheCysValIleLeuGlySerCysGlyIleThrLeuVal180 185190SerTyrAlaLysIleProSerAlaArgGlyArgHisArgAlaPheSer195200205ThrCysSerSerHisL euThrValValLeuIleTrpTyrGlySerThr210215220IlePheLeuHisValArgThrSerValGluSerSerLeuAspLeuThr225230 235240LysAlaIleThrValLeuAsnThrIleValThrProValLeuAsnPro245250255PheIleTyr ThrLeuArgAsnLysAspValLysGluAlaLeuArgArg260265270ThrValLysGlyLys275(2) INFORMATION FOR SEQ ID NO:63:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 273 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:63:LeuIlePheAlaLeuPheLeuSerMetTyrLeuValThrValLeuGly15 1015AsnLeuLeuIleIleMetAlaIleIleThrGlnSerHisLeuHisThr202530ProMetTyrPhePheLeu SerPheValAspIleCysPheThrSerThr354045ThrIleProLeuValAsnIleTyrThrGlnSerLysSerIleThrTyr50 5560GluAspCysIleSerLeuValPheAlaGluLeuGlyAsnPheLeuLeu65707580AlaValMetAlaTyrAspAr gTyrValAlaXaaCysHisProLeuCys859095TyrThrValIleValAsnHisArgLeuCysIleLeuLeuLeuLeuLeu100 105110SerTrpValIleSerIlePheArgAlaPheIleGlnSerLeuIleVal115120125LeuGlnLeuThrPheCy sGlyAspValLysIleProHisPhePheCys130135140GluLeuAsnGlnLeuSerGlnLeuThrCysSerAspAsnPheProSer145150 155160HisLeuIleMetAsnLeuValProValMetLeuAlaAlaIleSerPhe165170175SerGlyIleL euTyrSerTyrPheSerIleSerThrValGlnGlyLys180185190TyrLysAlaPheSerThrCysAlaSerHisLeuSerIleValSerLeu 195200205PheTyrSerThrGlyLeuGlyValTyrValSerSerAlaValValGln210215220SerSerHisSerAla AlaSerAlaSerValMetTyrThrValValPro225230235240MetLeuAsnProPheIleTyrSerLeuArgAsnLysAspValLysArg 245250255AlaLeuGluArgLeuLeuGluGlyAsnCysLysValHisHisTrpThr260265270Gly(2) INFORMATION FOR SEQ ID NO:64:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 269 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:64:LeuPheTyrAlaLeuPheLeuValMetTyrLeuThrThrIleL euGly151015AsnLeuLeuIleIleValLeuValGlnLeuAspSerGlnLeuHisThr2025 30ProMetTyrLeuPheLeuSerAsnLeuSerPheSerAspLeuCysPhe354045SerSerLeuLysLeuLeuGlnAsnMetArgSerGlnAspThr SerIle505560ProTyrGlyGlyCysLeuAlaGlnThrTyrPhePheMetValPheGly657075 80AspLeuSerPheLeuLeuValAlaMetAlaTyrAspArgTyrValAla859095IleCysPheLeuProHisTyrThrSerIleMetSerP roLysLeuCys100105110ThrCysLeuValLeuLeuLeuTrpMetLeuThrThrSerHisMetMet115120 125ThrLeuLeuAlaAlaArgLeuSerPheCysGluAsnAsnTrpLeuAsn130135140PhePheCysAspLeuPheValLeuLeuLysIleAlaCysSer AspThr145150155160TyrIleAsnGluLeuPheIleMetSerThrLeuLeuIleIleIlePro165170 175PhePheLeuIleValMetSerTyrAlaLysValProSerThrGlnGly180185190IleCysLysValPheSerThrCysGlySer HisLeuSerValValSer195200205LeuPheTyrGlyThrIleIleGlyLeuTyrLeuCysProAlaGlyAsn210215 220AsnSerThrValLysGluMetValMetAlaMetMetTyrThrValVal225230235240ThrProMetIleAsnProPheIleTyrSe rLeuArgAsnArgAspLeu245250255ArgAlaLeuIleArgValIleCysSerMetIleThrLeu260265 (2) INFORMATION FOR SEQ ID NO:65:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 286 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:65:LeuLeuPhePheLeuSerLeuLeuXaaTyrValLeuValLeuThrGl u151015AsnMetLeuIleIleIleAlaIleArgAsnHisProThrLeuHisLys20253 0ProMetTyrPhePheLeuPheLeuGluIleTrpTyrValThrValThr354045IleProLysLeuMetGlyPheIleGlySerLysGluAsnHisGly Gln505560LeuIleSerPhePheAlaCysMetThrGlnLeuTyrPhePheLeuGly65707580LeuGlyCysThrGluCysValLeuLeuAlaValMetAlaTyrAspArg859095TyrValAlaIleCysHisProLeuHisTyrProValIleVa lSerSer100105110ArgIleGlxValLeuGlySerTrpAlaGlyGlyPheGlyIleSerMet115120 125ValLysValPheLeuIleSerArgLeuSerTyrCysGlyProAsnThr130135140IleAsnHisPhePheCysAspValSerProLeuLeuAsnLeuSerC ys145150155160ThrAspMetSerThrAlaGluLeuThrAspPheValIleAlaIlePhe165170 175IleLeuLeuGlyProLeuSerValThrGlyAlaSerTyrMetArgIle180185190ProSerAlaAlaGlyArgHisLysAlaPheSer ThrCysAlaSerHis195200205LeuThrValValIleIlePheTyrAlaAlaSerIlePheIleTyrAla210215 220ArgProLysAlaLeuSerAlaPheThrAspAsnLysLeuValSerVal225230235240LeuTyrAlaValIleValProLeuPheAsnPro IleIleTyrCysLeu245250255ArgAsnGlnAspValLysArgAlaLeuArgArgThrLeuHisLeuAla2602 65270GlnAspGlnGluAlaAsnThrAsnLysGlySerLysIleGly275280285(2) INFORMATION FOR SEQ ID NO:66:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 275 amino acids (B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:66:LeuPhePheAlaLeuPheLeuIleMetTyrLeuThrThrPheLeuGly1510 15AsnLeuLeuIleValValLeuValGlnLeuAspSerHisLeuHisThr202530ProMetTyrLeuPheLeuSerAsnLeuSer PheSerAspLeuCysPhe354045SerSerValThrMetLeuLysLeuLeuGlnAsnIleGlnSerGlnVal5055 60ProSerIleSerTyrAlaGlyCysLeuTrpIlePhePhePheLeuLeu65707580PheGlyTyrLeuGlyAsnPheLeuLeuValAl aMetAlaTyrAspArg859095TyrValAlaIleCysPheProLeuHisTyrThrAsnIleMetSerHis1001 05110LysLeuCysThrCysLeuLeuLeuValPheTrpIleMetArgSerSer115120125HisAlaMetMetIleThrLeuIleAlaAl aArgLeuSerPheCysGlu130135140AsnAsnValLeuLeuAsnPhePheCysAspLeuPheValLeuLeuLys145150 155160LeuAlaCysSerAspThrTyrValAsnGluLeuMetIleHisIleMet165170175GluValIleIleIleValIleP roPheValLeuIleValIleSerTyr180185190AlaLysValProSerThrGlnSerIleHisLysValPheSerThrCys195 200205GlySerHisLeuSerValValSerLeuPheTyrGlyThrIleIleGly210215220LeuTyrLeuCysProSerGlyAspAsn PheSerLeuLysGlySerLeu225230235240ThrValValThrProIleMetProPheIleTyrSerLeuArgAsnArg245 250255AspMetLysGlnAlaLeuIleArgValThrCysSerLysLysIleSer260265270LeuProTrp 275(2) INFORMATION FOR SEQ ID NO:67:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 284 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:67:LeuPheTyrAlaLeuPheLeuAlaMetTyrLeuTh rThrLeuLeuGly151015AsnLeuIleIleIleIleLeuIleLeuLeuAspSerHisLeuHisThr2025 30ProMetTyrLeuPheLeuSerAsnLeuSerPheAlaAspLeuCysPhe354045SerSerLeuLysLeuLeuGlnAsnMetGlnSer GlnValProSerIle505560ProTyrAlaGlyCysLeuAlaGlnIleTyrPhePheLeuPhePheGly657075 80AspLeuGlyAsnPheLeuLeuValAlaMetAlaTyrAspArgTyrVal859095AlaIleCysPheProLeuHisTyrMetSe rIleMetSerProLysIle100105110GlxValSerLeuValValLeuSerTrpValLeuThrThrPheHisAla115120 125MetLeuHisThrLeuIleMetAlaArgLeuSerPheCysGluAspSer130135140ValIleProHisTyrPheCysAspMetSerThrL euLeuLysValAla145150155160CysSerAspThrHisAspAsnGluLeuAlaIlePheIleLeuGlyGly165 170175ProIleValValLeuProPheLeuLeuIleIleValSerTyrAlaArg180185190IleValSerSerIlePheLys ValProSerSerGlnSerIleHisLys195200205AlaPheSerThrCysGlySerHisLeuSerValValSerLeuPheTyr21021 5220GlyThrValIleGlyLeuTyrLeuCysProSerAlaAsnAsnSerGlu225230235240ValLysGluThrValMetSer IleTyrThrMetValProMetLeuAsn245250255ProPheIleTyrSerLeuArgAsnArgAspIleLysAspAlaLeuGlu260 265270LysIleMetCysLysLysGlnIleProSerPheLeu275280(2) INFORMATION FOR SEQ ID NO:68:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 277 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:68:LeuPheTyrAlaLeuPheLeuAlaMetTyrLeuThrIleIleLeuGly1510 15AsnLeuLeuIleIleValLeuValArgLeuAspSerHisLeuHisMet202530TyrLeuPheLeuSerAsnLeuSerPheSerAspLeuCys PheSerSer354045ValThrTrpLysLeuLeuGlnAsnMetGlnSerGlnValProSerIle505560 SerTyrThrGlyCysLeuThrGlnLeuTyrPhePheMetValPheGly65707580AspTrpSerPheLeuLeuValValMetAlaTyrAspArgTy rValAla859095IleCysPheProLeuArgTyrThrThrIleMetSerThrLysPheCys100105 110AlaSerLeuValLeuLeuLeuTrpMetLeuThrMetArgHisAlaLeu115120125LeuHisThrLeuLeuIleAlaArgLeuSerPheCysGl uAspSerVal130135140IleLeuHisPhePheCysAspIleSerAlaLeuLeuLysLeuSerCys145150155 160SerAspIleTyrValAsnGluLeuMetIleTyrIleLeuGlyGlyLeu165170175IleIleIleIleProPheLeuLeuIleValM etSerTyrValArgIle180185190PhePheSerIleLeuLysPheProSerIleGlnAspIleTyrLysVal195200 205PheSerThrCysGlySerHisLeuSerValValThrLeuPheTyrGly210215220ThrIlePheGlyIleTyrLeuCysProSerGlyAsn AsnSerThrVal225230235240LysGluIleLeuThrValValThrProMetIleAsnProPheIleTyr245 250255SerLeuArgAsnArgAspTrpArgAlaLeuIleArgValIleCysThr260265270LysLysIleSerLeu 275(2) INFORMATION FOR SEQ ID NO:69:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 274 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:69:ValPheTyrAlaLeuPheLeuSerMetTyrLeuThrIl eValLeuGly151015AsnLeuIleIleIleIleLeuIleHisLeuAspSerHisLeuHisThr2025 30ProMetTyrLeuPheLeuSerAsnLeuSerPheSerAspLeuCysPhe354045SerSerLeuLysLeuLeuGlnAsnMetGlnSerGln ValProSerIle505560ProPheAlaGlyCysLeuThrGlnLeuTyrPheTyrLeuTyrPheAla657075 80AspLeuGluSerPheLeuLeuValAlaMetAlaTyrAspArgTyrVal859095AlaIleCysPheProLeuHisTyrMetSerIl eMetSerProLysLeu100105110CysValSerLeuTrpLeuSerTrpValLeuThrThrPheHisAlaMet115120 125LeuHisThrLeuIleMetAlaArgLeuSerPheCysAlaAspLeuPro130135140HisPhePheCysAspIleSerProLeuLeuLysLeuS erCysSerAsp145150155160ThrHisValAsnGluLeuValIlePheLeuGlyLeuValIleValIle165 170175ProPheValLeuIleIleValSerTyrAlaArgValValAlaSerIle180185190LeuLysValProSerValArgGly IleHisLysIlePheSerThrCys195200205GlySerHisLeuSerValValSerLeuPheTyrGlyThrIleIleGly210215 220LeuTyrLeuCysProSerAlaAsnAsnSerThrValLysGluThrLeu225230235240ThrValValThrProLeuProPhe IleTyrSerLeuArgAsnArgAsp245250255MetLysGluAlaLeuIleArgValLeuCysLysLysLysIleThrPhe260 265270CysLeu(2) INFORMATION FOR SEQ ID NO:70:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 345 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:70:LeuAla IleAlaValLeuSerLeuThrLeuLeuGlyThrPheThrVal151015LeuGluAsnLeuLeuValLeuCysValIleLeuHisSerArgSerLeu 202530ArgCysArgProSerTyrHisPheIleGlySerLeuAlaValAlaAsp354045LeuL euGlySerValIlePheValTyrSerPheValAspPheHisVal505560PheHisArgLysAspSerProAsnValPheLeuPheLysLeuGlyGly65 707580ValThrAlaSerPheThrAlaSerValGlySerLeuPheLeuThrAla859095 IleAspArgTyrIleSerIleHisProProIleAlaTyrLysArgIle100105110ValArgArgProLysAlaValValAlaPheCysLeuMetThrIleAla115120125IleValIleAlaValLeuProLeuLeuGlyTrpAsnCysLysLysLeu130135140GlnSe rValCysCysAspIlePheProLeuIleAspGlyThrTyrLeu145150155160MetPheTrpIleGlyValThrSerValLeuLeuLeuPheIleValTyr165170175AlaTyrMetTyrIleLeuTrpLysAlaHisSerHisAlaValArgAla1801851 90GlnArgGlyThrGlnLysSerIleIleIleHisThrSerGluAspGly195200205LysValGlnValThrArgProAspGlnAlaArgMetAspIleAr gLeu210215220AlaLysThrLeuValLeuIleLeuValValLeuIleIleCysTrpGly225230235 240ProLeuLeuAlaIleMetValTyrAspValPheGlyLeuLeuIleLys245250255ThrValPheAlaPheCysSerLeuLeuIleAsnSerT hrValAsnPro260265270IleIleTyrAlaLeuArgSerLysAspLeuArgHisAlaPheArgSer275280 285TrpProSerCysGluGlyThrAlaGlnProLeuAspAsnSerMetGly290295300AspSerAspCysLeuHisLysHisAlaAsnAsnThrAlaSer MetHis305310315320ArgAlaAlaGluSerCysIleLysSerThrValLysLeuAlaLeuVal325330 335SerThrAspThrSerAlaGluAlaLeu340345(2) INFORMATION FOR SEQ ID NO:71:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 349 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single (D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:71:LysAlaLeuLeuIleValAlaTyrSerPheThrIleValPheSerLeu151015PheGlyAsnVal LeuValCysHisTyrIlePheLysAsnGlnArgLys202530IleSerAlaThrSerLeuPheIleValAsnLeuAlaValAlaAspIle35 4045IleGluThrLeuLeuAsnThrProPheThrLeuValArgPheValAsn505560SerThrTrpTyrPheGlyL ysGlyMetLeuHisValSerArgPheAla65707580GlnTyrCysSerLeuHisValSerAlaLeuIleLeuThrAlaIleAla 859095ValAspArgHisGlnValIleMetProLeuLysProArgIleSerIle100105110ThrLysGl yValIleTyrIleAlaValIleTrpValMetThrPhePhe115120125SerLeuProHisAlaIleCysGlnLysLeuPheThrPheLysTyrSer130 135140GluAspIleValArgSerLeuCysLeuAspProPheProGluProAla145150155160AspLeuP heTrpLysTyrLeuAspIleAlaThrPheIleLeuLeuTyr165170175LeuLeuProLeuPheIleIleSerValAlaTyrAlaArgValAlaLys 180185190LysLeuTrpLeuCysAsnThrIleGlyAspValThrThrGluGlnTyr195200205Leu AlaLeuArgArgLysLysLysThrThrValLysMetLeuValLeu210215220ValValValLeuPheAlaLeuCysTrpPheProLeuAsnCysTyrVal225 230235240LeuLeuLeuSerSerLysAlaIleHisThrAsnAsnAlaLeuTyrPhe245250255 AlaPheHisTrpPheAlaMetSerSerThrCysTyrAsnProPheIle260265270TyrCysTrpLeuAsnGluAsnPheArgValGluLeuLysAlaLeu Leu275280285SerMetGlnProProProLysProGluAspArgLeuProSerProVal290295300Pr oSerPheArgValAlaTrpThrGluLysSerHisGlyArgArgAla305310315320ProLeuProAsnHisHisLeuProSerSerGlnIleGlnSerGly Lys325330335ThrAspLeuSerSerValGluProValValAlaMetSer340345(2) INFORMATION FOR SEQ ID NO:72:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 301 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:72:IlePheThrIleAlaLeuAlaTyrGlyAlaValIleIleLeuGlyVal1 51015SerGlyAsnLeuAlaLeuIleIleIleIleLeuLysGlnLysGluLeu202530IleLeuIle ValAsnLeuSerPheSerAspLeuLeuValAlaValTrp354045LeuProPheThrPheValTyrThrLeuIleCysHisTrpValPheGly50 5560GluCysCysLysLeuAsnProPheValGlnCysValSerIleThrVal65707580SerIlePheS erLeuValLeuIleAlaValGluArgHisGlnLeuIle859095IleAsnProArgGlyTrpArgProAsnAsnArgHisAlaTyrIleGly 100105110IleThrValIleTrpValIleAlaValAlaSerSerLeuProPheVal115120125IleTyrG lnIleLeuThrAspGluProPheGlnAsnValSerLeuAla130135140AlaPheLysAspLysTyrValCysPheAspLysPheProSerAspSer145 150155160HisArgLeuSerTyrThrThrLeuLeuLeuValLeuGlnTyrPheGly165170175 ProLeuCysPheIlePheIleCysTyrPheLysIleTyrIleArgLeu180185190LysArgArgAsnAsnMetMetLysIleArgAspSerLysTyrArgSer 195200205SerGluThrLysArgIleAsnValMetLeuLeuSerIleValValAla210215220PheAla ValCysTrpLeuProLeuThrIlePheAsnIleValPheAsp225230235240TrpAsnHisGlnIleIleAlaThrCysAsnHisAsnLeuLeuPheLeu245250255LeuCysHisLeuThrLeuSerThrCysValAsnProIlePheTyrGly26026527 0PheLeuAsnLysAsnPheGlnArgAspLeuGlnPhePhePheAsnPhe275280285CysAspPheArgSerArgAspGlyArgThrThrArgLeu 290295300(2) INFORMATION FOR SEQ ID NO:73:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 334 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:73:LeuThrSe rValValPheIleLeuIleCysCysPheIleIleLeuGlu151015AsnIlePheValLeuLeuThrIleTrpLysThrLysLysPheHisArg 202530ProMetTyrTyrPheIleGlyAsnIleAlaLeuSerAspLeuIleAla354045GlyVal AlaTyrThrAlaAsnLeuLeuLeuSerGlyAlaThrThrTyr505560LysLeuThrProAlaGlnTrpPheLeuArgGluGlySerMetPheVal65 707580AlaLeuSerLeuSerValPheSerLeuLeuAlaIleAlaIleGluArg859095Ty rIleThrMetLeuLysMetLeuHisAsnGlySerAsnAsnPheArg100105110LeuPheLeuLeuIleSerAlaCysTrpValIleSerLeuIleLeuGly 115120125GlyLeuProIleMetGlyTrpAsnCysIleSerAlaLeuSerSerCys130135140SerThrV alLeuProLeuTyrHisLysHisTyrIleLeuPheCysThr145150155160LeuIleValPheThrLeuLeuLeuLeuSerIleValIleLeuTyrCys 165170175ArgIleTyrSerLeuValArgThrArgSerArgArgLeuThrPheArg180185190LysAsnIleSerLysAlaSerArgSerSerGluAsnValAlaLeuLeu195200205LysThrValIleIleValLeuSerValPheIleAlaCysTrpAlaP ro210215220LeuPheIleLeuLeuLeuLeuAspValGlyCysLysValLysThrCys225230235240AspIleLeuPheArgAlaGluTyrPheLeuValIleAlaValIleAsn245250255SerGlyThrAsnProIleIleTyrThrLeuThrAsnLys GluMetArg260265270ArgAlaPheIleArgIleMetCysCysLysCysProSerGlyAspSer275280 285AlaGlyLysPheLysArgProIleIleAlaGlyMetGluPheSerArg290295300SerLysSerAspAsnSerSerHisProGlnLysAspGluGlyAsp Asn305310315320ProGluThrIleMetSerSerGlyAsnValAsnSerSerSer325330(2) INFORMATION FOR SEQ ID NO:74:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 236 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:74:IleThrTyrTyrIleLeuIleGlyLeuCysAlaValValGlyAsnIle 151015LeuLeuValIleTrpValValLysLeuAsnArgThrLeuArgThrThr202530 ThrPheTyrPheIleValSerIleAlaLeuAlaAspIleAlaValLeu354045ValIleProLeuAlaIleAlaSerAlaTrpArgSerArgCysThrSer 505560AsnCysLeuPheMetSerCysValLeuLeuValPheThrHisAlaSer65707580I leMetSerLeuLeuAlaIleAlaValAspArgTyrLeuArgValLys859095LeuThrValArgTyrArgThrValThrThrGlnArgArgIleTrpLeu100105110PheLeuGlyLeuCysTrpLeuValSerPheLeuValGlyLeuThrPro115120125 TrpGlyTrpAsnArgLysValThrLeuGluLeuSerGlnAsnSerSer130135140ThrLeuArgGluPheLysThrProLysSerLeuPheLeuValLeuPhe 145150155160LeuPheAlaLeuCysTrpLeuProLeuSerIleIleAsnPheValSer165170 175TyrPheAsnValLysIleProGluThrLeuLeuGlyIleLeuLeuSer180185190HisAlaAsnSerLeuProIleValTyrAlaCysLysLysL ysPheLys195200205GluThrTyrPheValIleLeuArgAlaCysArgLeuCysGlnThrSer210215220 AspSerLeuAspSerAsnLeuGluGlnThrThrGlu225230235(2) INFORMATION FOR SEQ ID NO:75:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 322 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single (D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:75:AlaIleLeuIleSerPheIleTyrSerTrpCysLeuValGlyLeuCys151015GlyAsnSerMet ValIleTyrValIleLeuArgTyrAlaLysMetLys202530ThrAlaThrAsnIleTyrIleLeuAsnIleAlaIleAlaAspGluLeu35 4045LeuValProPheLeuValThrSerThrLeuLeuArgHisTrpProPhe505560GlyAlaLeuLeuCysArgLe uValLeuSerValAspAlaValAsnMet65707580PheThrSerIleTyrCysLeuThrValLeuSerValAspArgTyrVal 859095AlaValValHisProIleLysAlaAlaArgTyrArgArgProThrVal100105110AlaLysVal ValAsnLeuGlyValTrpValLeuSerLeuLeuValIle115120125LeuProIleTrpPheSerArgThrAlaAlaAsnSerAspGlyThrVal130 135140AlaCysAsnMetIleTrpGluProAlaGlnPheTrpLeuValGlyPhe145150155160ValLeuTy rThrPheLeuMetPheLeuLeuProValGlyAlaIleCys165170175LeuCysTyrValLeuIleIleAlaLysMetArgMetValAlaLeuLys 180185190AlaGlyTrpGlnGlnArgLysArgSerGluArgLysIleThrLeuVal195200205MetM etValValMetValPheValIleCysTrpPheTyrValValGln210215220LeuValAsnValPheAlaGluGlnAspAspAlaThrValSerGlnLeu225 230235240SerValIleLeuGlyTyrAlaAsnSerCysAlaAsnProIleLeuTyr245250255 GlyPheLeuSerAspAsnPheLysArgSerPheGlnArgIleLeuCys260265270LeuSerLeuAsnAlaAlaGluGluProValAspTyrTyrAlaThrA la275280285LeuLysSerArgAlaTyrSerValGluAspPheGlnProGluAsnLeu290295300Glu SerGlyGlyValPheArgAsnCysThrCysAlaSerArgIleSer305310315320ThrLeu(2) INFORMATION FOR SEQ ID NO:76:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 298 amino acids (B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:76:ValThrAsnTyrIlePheLeuLeuLeuCysLeuCysGlyLeuValGly1510 15AsnGlyLeuValLeuTrpPhePheGlyPheSerIleLysArgThrPro202530PheSerIleTyrIleTyrPheLeuHisIl eAlaSerAlaAspGlyIle354045TyrLeuPheSerLysAlaValIleAlaLeuLeuAsnMetGlyThrPhe5055 60LeuGlySerPheProAspTyrValArgArgValSerArgIleValGly65707580LeuThrPhePheAlaGlyValSerLeuLeu ProAlaIleSerIleGlu859095ArgCysValSerValIlePheProMetTrpTyrTrpArgArgArgPro100 105110LysArgLeuSerAlaGlyValCysAlaLeuLeuTrpLeuLeuSerPhe115120125LeuValThrSerIleHisAsnTyrPhe CysLeuLeuGlyHisGluAla130135140SerGlyThrAlaCysLeuAsnMetAspIleSerLeuLeuGlyIleLeu145150 155160LeuPhePheLeuPheCysProIleMetValLeuProCysIleAlaLeu165170175LeuHisValGluCysArgAla ArgArgArgGlnArgSerAlaLysLeu180185190AsnHisValValLeuAlaIleValSerValPheLeuValSerSerIle195 200205TyrLeuGlyIleAspTrpPheLeuPheTrpValPheGlnIleProAla210215220ProPheProGluTyrValArgAspLe uCysIleCysIleAsnSerSer225230235240AlaLysProIleValTyrPheIleAlaGlyArgAspLysSerGlnArg245 250255LeuTrpGluProLeuArgValValPheGlnArgAlaLeuArgAspGly260265270AlaGluProGlyA spAlaAlaSerSerThrProAsnThrValThrMet275280285GluMetGlnCysProSerGlyAsnAlaSer290295(2) INFORMATION FOR SEQ ID NO:77:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 299 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:77:ThrThrGluAlaValLeuAsnThrPheIleIlePheValGlyGlyPro 151015AlaIleValLeuIleThrGlnLeuLeuThrAsnArgValLeuGlyTyr202530 SerThrProThrIleTyrMetArgAsnLeuTyrSerThrAsnPheLeu354045ThrLeuThrValLeuProPheIleValLeuSerAsnGlnTrpLeuLeu 505560ProAlaCysTyrValAlaSerCysLysPheLeuSerValIleTyrTyr65707580 SerSerCysThrValGlyPheAlaThrValAlaLeuIleAlaAlaAsp859095ArgTyrArgValLeuHisLysArgThrTyrAlaArgGlnSerTyrA rg100105110SerLeuLeuLeuThrTrpLeuAlaGlyLeuIlePheSerValProAla115120125 AlaValTyrThrThrValValMetHisHisAspAlaAsnAspThrAsn130135140AsnThrAsnGlyHisAlaThrCysValLeuTyrPheValAlaGluGlu 145150155160ValHisThrValLeuLeuSerTrpLysValLeuLeuThrMetValTrp165170 175GlyAlaAlaProValIleLeuPheTyrAlaPhePheTyrSerThrVal180185190GlnArgThrSerGlnLysGlnArgSerArgThrLeuThr PheValSer195200205ValLeuLeuIleSerPheValAlaLeuGlnThrProTyrValSerLeu210215220MetIlePheAsnSerTyrAlaThrThrAlaTrpProMetCysGluHis225230235240LeuThrLeuArgArgThrIleGlyThrLeuAlaArgVa lValProHis245250255LeuHisCysLeuIleAsnProIleLeuTyrAlaLeuLeuCysHisAsp260265 270PheLeuGlnArgMetArgGlnCysPheArgGlyGlnLeuIleAspArg275280285AlaPheLeuArgSerGlnGlnAsnGlnArgAla 290295(2) INFORMATION FOR SEQ ID NO:78:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 283 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:78:LeuGlyValTrpLeuMet IleValGlyThrPheLeuLeuValIleThr151015ThrIleLeuTyrTyrArgArgLysLysLysSerProSerAspThrTyr20 2530IleCysAsnLeuAlaValAlaAspLeuLeuIleValValGlyLeuPro354045PhePheLeuGluTyrAl aLysHisHisProLysLeuSerArgGluVal505560ValCysSerGlyLeuAsnAlaCysPheTyrIleCysLeuPheAlaGly6570 7580ValCysPheLeuIleAsnLeuSerMetAspArgTyrCysValIleVal859095TrpGlyValGlu LeuAsnArgValArgAsnAsnLysArgAlaThrCys100105110TrpValValIlePheTrpIleIleAlaValLeuMetGlyMetProHis11 5120125TyrIleMetTyrSerHisThrAsnAsnGluCysValGlyTrpPheAla130135140AsnGluThrSerCysTrp PheProValPheLeuAsnThrLysValAsn145150155160IleCysGlyTyrLeuAlaProIleAlaLeuMetAlaTyrTyrAsnArg 165170175MetValArgPheIleIleAsnTyrValGlyLysTrpPheMetGlnThr180185190LeuHi sValLeuLeuValValValValSerPheAlaSerPheTrpPhe195200205ProPheAsnLeuAlaLeuPheLeuGluSerIleArgLeuIleAlaGly 210215220ValTyrAsnAspThrLeuGlnAsnValIleIlePheCysLeuTyrVal225230235240GlyG lnPheIleAlaTyrValArgAlaCysLeuAsnProGlyIleTyr245250255IleLeuValCysThrTrpPheLeuArgValPheAlaCysCysCysVal 260265270LysGlnGluIleProTyrGlnAspIleAspIle275280(2) INFORMATION FOR SEQ ID NO:79:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 295 amino acids (B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:79:ProValThrLeuPheLeuTyrGlyValValPheLeuPheGlySerIle15 1015GlyAsnPheLeuValIlePheThrIleThrTrpArgArgArgIleGln202530CysSerGlyAspValTyrPheIleAs nLeuAlaAlaAlaAspLeuLeu354045PheValCysThrLeuProLeuTrpMetGlnTyrLeuLeuAspHisAsn5055 60SerLeuAlaSerLeuIleProCysThrLeuLeuThrAlaCysPheTyr65707580ValAlaIleThrAlaSerLeuCysPhe IleThrGluIleAlaLeuIle859095AspArgTyrTyrAlaIleValTyrMetArgTyrArgProValLysIle100 105110GlnAlaCysLeuPheSerIlePheTrpTrpIlePheAlaValIleIle115120125AlaIleProHisPheMetValVal IleThrLysLysAspAsnGlnCys130135140MetThrAspTyrAspTyrLeuGluValSerTyrProIleIleLeuAsn145150 155160ValGluLeuMetLeuGlyAlaPheValIleProLeuSerValIleSer165170175TyrCysTyrTyrArgIle SerArgIleValAlaValSerGlnSerArg180185190HisLysGlyArgIleValArgValLeuIleAlaTrpLeuValPheIle195 200205IlePheTrpLeuProTyrHisLeuThrLeuPheValAspThrIleIle210215220LysLeuLeuLysTrpIleSerSe rSerCysGluPheGluArgSerLeu225230235240LysArgAlaLeuIleLeuThrGluSerLeuAlaPheCysHisCysCys 245250255LeuAsnProLeuLeuTyrValPheValIleGlyThrLysPheArgLys260265270AsnTyrThrV alCysTrpProSerPheAlaSerAspSerPheProAla275280285MetTyrProGlyThrArgAla290295(2) INFORMATION FOR SEQ ID NO:80: (i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 31 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:80:AspAspAspAspAsnIleTrpSerIlePheAspTrpIleGlyTyrLeu1 51015AsnSerIleSerMetValIleTyrThrLeuPheLysLysLysLys202530(2) INFORMATION FOR SEQ ID NO:81: (i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 34 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:81:AspAspAspAspAsnIleTrpAsnIlePheSerThrIleGlyTyrLeu1 51015AsnSerIleSerProValSerValIleMetHisIleTyrGlyLysLys202530Lys Lys(2) INFORMATION FOR SEQ ID NO:82:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 29 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:82:AspAspAspAspGlyTyrSerIleTyrAspThrLeuValT hrPheAla151015IleAsnProValTyrIleThrValPheLysLysLysLys2025(2) INFORMATION FOR SEQ ID NO:83: (i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 31 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:83:AspAspAspAspAsnAlaTrpSerAlaPheAspTrpAlaLeuTyrLeu1 51015AsnSerIleSerMetAlaIleTyrThrTyrAlaLysLysLysLys202530(2) INFORMATION FOR SEQ ID NO:84: (i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 23 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:84:LeuPheSerPheIleThrTrpLeuGlyTyrAlaAsnSerSerLeuAsn1 51015ProIleIleTyrThrThrPhe20(2) INFORMATION FOR SEQ ID NO:85:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 23 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single (D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:85:TyrThrIleTyrSerSerSerValValPhePheAlaProSerLeuAla151015IleMetV alIleThrTyrThr20(2) INFORMATION FOR SEQ ID NO:86:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 22 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:86:IleTrpLeuThrS erAspIleMetSerThrSerSerIleLeuHisAsn151015LeuCysValIleSerPhe20(2) INFORMATION FOR SEQ ID NO:87:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 30 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:87:IleTrpSerIlePheSerSerAspIleValValGlyTyrAlaAsnHis15 1015SerSerLeuAlaIleMetCysProIleValIleTyrThrVal202530(2) INFORMATION FOR SEQ ID NO:88:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 29 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:88:IlePheThrIlePheSerSerAspIleAlaValGlyTyrAlaAsnHis15 1015SerSerAlaAlaIleMetProIleValIleTyrSerVal2025(2) INFORMATION FOR SEQ ID NO:89:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 24 amino acids(B ) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:89:LysAsnAlaSerAlaLeuLeuSerValIleIleIleAsnSerIleGly1510 15GlyAsnValValThrAlaValSer20(2) INFORMATION FOR SEQ ID NO:90:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 22 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi ) SEQUENCE DESCRIPTION: SEQ ID NO:90:TyrPheLeuMetSerLeuAlaValThrAspLeuValValSerPheVal151015MetProValSerAlaLeu20(2) INFORMATION FOR SEQ ID NO:91:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 23 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:91:AlaIleThrLysIleAlaIleThrTrpAlaIleSerGlyValSer Val151015ProPheIleProValTrpGly20(2) INFORMATION FOR SEQ ID NO:92:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 24 amino acids(B) TYPE: amino acid (C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:92:LeuGlyIleIlePheGlyThrPheIleIleIleTrpLeuProPhePhe151015IleThrAsnLeuValSerProIle20(2) INFORMATION FOR SEQ ID NO:93:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 23 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:93: IleTrpIleSerLeuAspValLeuPheSerThrAlaSerSerIleMet151015HisLeuCysAlaIleSerLeu20(2) INFORMATION FOR SEQ ID NO:94:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 23 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:94:GlyTyrThrIleTyrSerThrLeuValThrPheTyrIleProSerVal 151015IleMetValIleThrTyrGly20(2) INFORMATION FOR SEQ ID NO:95:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 23 amino acids(B) TYPE: amino acid (C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:95:LeuLeuAsnPhePheAsnTrpIleGlyTyrLeuAsnSerLeuIleAsn151015 ProValIleTyrThrLeuPhe20(2) INFORMATION FOR SEQ ID NO:96:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 25 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:96:TyrA laIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn151015CysProPheIleValThrLeuAsnIle20 25(2) INFORMATION FOR SEQ ID NO:97:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 25 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:97:TyrAlaIlePheValLeuTyrAlaThrAlaTrpLeu SerPheLeuAsn151015CysProPheIleValThrLeuAsnIle2025(2) INFORMATION FOR SEQ ID NO:98:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 25 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:98:TyrAlaIlePheValLeuTyrAlaThrAlaTrpLeuThrPheLeuAsn15 1015CysProPheIleValThrLeuAsnIle2025(2) INFORMATION FOR SEQ ID NO:99:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 25 amino acids(B) TYPE: amino acid (C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:99:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuThrPheLeuAsn151015CysProPheIleValThrLeuAsnIle2025(2) INFORMATION FOR SEQ ID NO:100:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 25 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:100:TrpAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn151015CysProPheIleValThrLeuAsnIle2025(2) INFORMATION FOR SEQ ID NO:101:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 25 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:101:TrpAlaIlePhe ValLeuTyrAlaThrAlaTrpLeuSerPheLeuAsn151015CysProPheIleValThrLeuAsnIle2025(2) INFORMATION FOR SEQ ID NO:102:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 25 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:102:TrpAlaIlePheValLeuTyrAlaThrAlaTrpLeuThrPheL euAsn151015CysProPheIleValThrLeuAsnIle2025(2) INFORMATION FOR SEQ ID NO:103:(i) SEQUENCE CHARACTERISTICS:(A ) LENGTH: 25 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:103:TrpAlaIlePheValLeuTyrAlaSerAlaTrpLeuThrPheLeuAsn15 1015CysProPheIleValThrLeuAsnIle2025(2) INFORMATION FOR SEQ ID NO:104:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 25 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:104:TyrAlaValPheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn151015Met ProPheIleValThrLeuAsnIle2025(2) INFORMATION FOR SEQ ID NO:105:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 25 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide( xi) SEQUENCE DESCRIPTION: SEQ ID NO:105:TyrAlaValPheValLeuTyrAlaThrAlaTrpLeuSerPheLeuAsn151015MetProPheIleValThrLeuAsnIle 2025(2) INFORMATION FOR SEQ ID NO:106:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 25 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:106:TyrAlaValPheValLeuT yrAlaThrAlaTrpLeuThrPheLeuAsn151015MetProPheIleValThrLeuAsnIle2025(2) INFORMATION FOR SEQ ID NO:107:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 25 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:107:TyrAlaValPheValLeuTyrAlaSerAlaTrpLeuThrPheLeuAsn 151015MetProPheIleValThrLeuAsnIle2025(2) INFORMATION FOR SEQ ID NO:108:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 30 amino acids (B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:108:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn1510 15CysValThrAlaSerIleProPheIleValThrLeuAsnIle202530(2) INFORMATION FOR SEQ ID NO:109:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 32 amino acids (B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:109:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn1510 15CysThrSerSerIleValValThrAlaSerIleValThrLeuAsnIle202530(2) INFORMATION FOR SEQ ID NO:110:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 27 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:110:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn15 1015ValThrLeuAsnIleCysThrSerSerIleVal2025(2) INFORMATION FOR SEQ ID NO:111:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 31 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:111:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn151015T hrAlaSerIleLeuAsnLeuMetPheIleValThrLeuAsnIle202530(2) INFORMATION FOR SEQ ID NO:112:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 31 amino acids(B) TYPE: amino acid( C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:112:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn151015 MetAlaSerIleLeuAsnLeuProPheIleValThrLeuAsnIle202530(2) INFORMATION FOR SEQ ID NO:113:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 31 amino acids(B) TYPE: amino acid (C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:113:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn151015 SerGlyIleLeuLeuLeuAlaProPheIleValThrLeuAsnIle202530(2) INFORMATION FOR SEQ ID NO:114:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 32 amino acids(B) TYPE: amino acid (C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:114:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn151015 MetSerGlyIleLeuLeuLeuAlaProPheIleValThrLeuAsnIle202530(2) INFORMATION FOR SEQ ID NO:115:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 35 amino acids(B) TYPE: amino acid (C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:115:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn1510 15SerGluLeuSerValTyrThrLeuThrValCysProPheIleValThr202530LeuAsnIle35(2) INFORMATION FOR SEQ ID NO:116:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 35 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:116:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn1 51015MetSerGluLeuSerValTyrThrLeuThrValProPheIleValThr202530LeuAsnIle35(2) INFORMATION FOR SEQ ID NO:117:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 36 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:117:TyrAlaIlePheValLeuTyrAlaSerAla TrpLeuAlaSerGluLeu151015SerValTyrThrLeuThrValSerPheLeuAsnCysProPheIleVal20 2530ThrLeuAsnIle35(2) INFORMATION FOR SEQ ID NO:118:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 31 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:118:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuAlaSerGluLeu151015SerValTyrThrLeuThrValProPheIleValThrLeuA snIle202530(2) INFORMATION FOR SEQ ID NO:119:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 43 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:119:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAla151015SerGluLeuSerValTyrAlaSerGluLeuSerSerThr LeuThrThr202530ValAsnMetProPheIleValThrLeuAsnIle3540(2) INFORMATION FOR SEQ ID NO:120:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 34 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:120:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn15 1015GlyGlyGluIleAlaLeuTrpSerLeuCysProPheIleValThrLeu202530AsnIle(2) INFORMATION FOR SEQ ID NO:121:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 31 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:121:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn 151015GlyGlyGluIleAlaLeuTrpSerLeuIleValThrLeuAsnIle202530(2) INFORMATION FOR SEQ ID NO:122:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 31 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:122:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuGlyGlyGluIle 151015AlaLeuTrpSerLeuAsnCysProPheIleValThrLeuAsnIle202530(2) INFORMATION FOR SEQ ID NO:123:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 30 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:123:TyrAlaIlePheValLeuTyrAlaGlyGlyGluIleAlaLeuTrpSer 151015LeuSerPheLeuAsnCysProPheIleValThrLeuAsnIle202530(2) INFORMATION FOR SEQ ID NO:124:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 37 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:124:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPhePhePhe 151015LeuLeuPheGlyTyrLeuGlyAsnPheLeuLeuAsnCysProPheIle202530 ValThrLeuAsnIle35(2) INFORMATION FOR SEQ ID NO:125:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 34 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:125:TyrAlaIlePheV alLeuTyrAlaSerAlaTrpLeuPhePhePheLeu151015LeuPheGlyTyrLeuGlyAsnPheLeuLeuProPheIleValThrLeu 202530AsnIle(2) INFORMATION FOR SEQ ID NO:126:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 45 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:126: TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn151015ThrAlaCysPheTyrValAlaIleThrAlaSerLeuCysPheI leThr202530GluIleAlaLeuIleProPheIleValThrLeuAsnIle354045(2) INFORMATION FOR SEQ ID NO:127:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 42 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:127:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuThrAlaCysPhe 151015TyrValAlaIleThrAlaSerLeuCysPheIleThrGluIleAlaLeu202530 IleCysProPheIleValThrLeuAsnIle3540(2) INFORMATION FOR SEQ ID NO:128:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 42 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:128:TyrAlaIlePheValLeuTyrAlaThrAlaCysPheTyrValAlaIle151015ThrAlaSerLeuCysPheIleThrGluIleA laLeuIleSerPheLeu202530AsnCysProPheIleValThrLeuAsnIle3540(2) INFORMATION FOR SEQ ID NO:129:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 42 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:129:TyrAlaIleThrAlaCysPheTyrValAlaIleThrAlaSerLeuCys1 51015PheIleThrGluIleAlaLeuIleAlaSerAlaTrpLeuSerPheLeu202530AsnCysProPhe IleValThrLeuAsnIle3540(2) INFORMATION FOR SEQ ID NO:130:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 40 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:130: TyrAlaIlePheValLeuTyrAlaThrAlaCysPheTyrValAlaIle151015IleThrGluIleAlaLeuIleSerAlaTrpLeuSerPheLeuA snCys202530ProPheIleValThrLeuAsnIle3540(2) INFORMATION FOR SEQ ID NO:131:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 39 amino acids (B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:131:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn1510 15AlaCysPheTyrIleCysLeuPheAlaGlyValCysPheLeuIlePro202530PheIleValThrLeuAsnIle 35(2) INFORMATION FOR SEQ ID NO:132:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 41 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:132:TyrAlaIlePheValLeuTyrAlaSerAlaTrpAsnAla CysPheTyr151015IleCysLeuPheAlaGlyValMetPheLeuIleLeuSerPheLeuAsn2025 30CysProPheIleValThrLeuAsnIle3540(2) INFORMATION FOR SEQ ID NO:133:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 38 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:133:TyrAlaIlePheValLeuTyrPheTyrIleCysLeuPheAlaGlyVal151015CysPheLeuIleAlaSerA laTrpLeuSerPheLeuAsnCysProPhe202530IleValThrLeuAsnIle35(2) INFORMATION FOR SEQ ID NO:134:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 34 amino acids (B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:134:TyrAlaIlePheValLeuTyrAlaSerValAspAlaValAsnMetPhe15 1015ThrSerAlaTrpLeuSerPheLeuAsnCysProPheIleValThrLeu202530AsnIle(2) INFORMATION FOR SEQ ID NO:135:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 34 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:135:TyrAlaIlePheSerValAspAlaValAsnMetPheThrValLeuTyr1 51015AlaSerAlaTrpLeuSerPheLeuAsnCysProPheIleValThrLeu202530AsnIle( 2) INFORMATION FOR SEQ ID NO:136:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 34 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:136:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerValAspAla151015ValAsnMetPheThrSerPheLeuAsnCysProPheIleValThrLeu202530AsnIle(2) INFORMATION FOR SEQ ID NO:137:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 33 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:137:TyrAlaIlePheValLeuTyrAlaSerAlaT rpLeuSerPheLeuAsn151015SerValAspAlaValAsnMetPheThrProPheIleValThrLeuAsn20 2530Ile(2) INFORMATION FOR SEQ ID NO:138:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 34 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:138:TyrAlaIlePheValLeu TyrAlaSerAlaTrpLeuSerPheLeuAsn151015CysProPheIleValSerValAspAlaValAsnMetPheThrThrLeu20 2530AsnIle(2) INFORMATION FOR SEQ ID NO:139:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 31 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:139:T yrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerValAspMet151015PheThrSerPheLeuAsnCysProPheIleValThrLeuAsnIle 202530(2) INFORMATION FOR SEQ ID NO:140:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 34 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:140: TyrAlaIleSerValAspAlaValAsnMetPheThrPheValLeuTyr151015AlaSerAlaTrpLeuSerPheLeuAsnCysProPheIleValThrL eu202530AsnIle(2) INFORMATION FOR SEQ ID NO:141:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 35 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:141:TyrAlaIlePheSerLeuSerValPheSerLeuLeuAlaIleValLeu151015TyrAlaSerAlaTrpLeuSerPheLeuAsn CysProPheIleValThr202530LeuAsnIle35(2) INFORMATION FOR SEQ ID NO:142:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 35 amino acids(B) TYPE: amino acid (C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:142:TyrAlaIlePheValLeuTyrAlaSerLeuSerValPheSerLeuLeu151015 AlaIleSerAlaTrpLeuSerPheLeuAsnCysProPheIleValThr202530LeuAsnIle35(2) INFORMATION FOR SEQ ID NO:143:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 35 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:143:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerLeuSerVal15 1015PheSerLeuLeuAlaIleSerPheLeuAsnCysProPheIleValThr202530LeuAsnIle 35(2) INFORMATION FOR SEQ ID NO:144:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 35 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:144:TyrAlaIlePheValLeuTyrAlaSerAlaTrpL euSerPheLeuSer151015LeuSerValPheSerLeuLeuAlaIleAsnCysProPheIleValThr2025 30LeuAsnIle35(2) INFORMATION FOR SEQ ID NO:145:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 34 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:145:T yrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn151015ProPheSerLeuSerValPheSerLeuLeuAlaIleIleValThrLeu202530AsnIle(2) INFORMATION FOR SEQ ID NO:146:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 30 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:146:TyrAlaIlePheValLeuTyrAlaThrAlaTrpLeuThrPheLeuAsn151015CysValThrAlaThrIleProPheIleValT hrLeuAsnIle202530(2) INFORMATION FOR SEQ ID NO:147:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 32 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:147:TyrAlaIlePheValLeuTyrAlaThrAlaTrpLeuSerPheLeuAsn151015CysThrSerSerIleValValThrAlaThrIle ValThrLeuAsnIle202530(2) INFORMATION FOR SEQ ID NO:148:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 27 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:148:TyrAlaIlePheValLeuTyrAlaThrAlaTrpLeuSerPheLeuAsn151015ValThrLeuAsnIleCysThrThrThrI leVal2025(2) INFORMATION FOR SEQ ID NO:149:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 31 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:149:TyrAlaI lePheValLeuTyrAlaThrAlaTrpLeuThrPheLeuAsn151015ThrAlaThrIleLeuAsnLeuMetPheIleValThrLeuAsnIle 202530(2) INFORMATION FOR SEQ ID NO:150:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 31 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:150:TyrAla IlePheValLeuTyrAlaThrAlaTrpLeuSerPheLeuAsn151015MetAlaThrIleLeuAsnLeuProPheIleValThrLeuAsnIle 202530(2) INFORMATION FOR SEQ ID NO:151:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 31 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:151:TyrA laIlePheValLeuTyrAlaThrAlaTrpLeuThrPheLeuAsn151015SerGlyIleLeuLeuLeuAlaProPheIleValThrLeuAsnIle 202530(2) INFORMATION FOR SEQ ID NO:152:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 32 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:152:Tyr AlaIlePheValLeuTyrAlaSerAlaTrpLeuThrPheLeuAsn151015MetThrGlyIleLeuLeuLeuAlaProPheIleValThrLeuAsnIle 202530(2) INFORMATION FOR SEQ ID NO:153:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 35 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:153: TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuThrPheLeuAsn151015ThrGluLeuThrValTyrThrLeuThrValCysProPheIleVal Thr202530LeuAsnIle35(2) INFORMATION FOR SEQ ID NO:154:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 35 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single (D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:154:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuThrPheLeuAsn151015MetThrGluLeu ThrValTyrThrLeuThrValProPheIleValThr202530LeuAsnIle35(2) INFORMATION FOR SEQ ID NO:155:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 36 amino acids (B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:155:TyrAlaIlePheValLeuTyrAlaThrAlaTrpLeuAlaThrGluLeu1510 15ThrValTyrThrLeuThrValThrPheLeuAsnCysProPheIleVal202530ThrLeuAsnIle35 (2) INFORMATION FOR SEQ ID NO:156:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 31 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:156:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuAlaThrGluL eu151015SerValTyrThrLeuThrValProPheIleValThrLeuAsnIle202530(2) INFORMATION FOR SEQ ID NO:157:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 43 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:157:TyrAlaIlePheValLeuTyrAlaThrAlaTrpLeuSerPheLeu Ala151015ThrGluLeuSerValTyrAlaSerGluLeuSerThrThrLeuThrThr2025 30ValAsnMetProPheIleValThrLeuAsnIle3540(2) INFORMATION FOR SEQ ID NO:158:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 34 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:158:TyrAlaIlePheValLeuTyrAlaThrAlaTrpLeuSerPheLeuAsn151015GlyGlyGluIleAlaLeuT rpThrLeuCysProPheIleValThrLeu202530AsnIle(2) INFORMATION FOR SEQ ID NO:159:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 31 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:159:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuThrPheLeuAsn151015Gly GlyGluIleAlaLeuTrpThrLeuIleValThrLeuAsnIle202530(2) INFORMATION FOR SEQ ID NO:160:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 31 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:160:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuGlyGlyGluIle151015A laLeuTrpThrLeuAsnCysProPheIleValThrLeuAsnIle202530(2) INFORMATION FOR SEQ ID NO:161:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 30 amino acids(B) TYPE: amino acid( C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:161:TyrAlaIlePheValLeuTyrAlaGlyGlyGluIleAlaLeuTrpThr151015 LeuSerPheLeuAsnCysProPheIleValThrLeuAsnIle202530(2) INFORMATION FOR SEQ ID NO:162:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 37 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:162:TyrAlaIlePheValLeuTyrAlaThrAlaTrpLeuSerPhePhePhe151015L euLeuPheGlyTyrLeuGlyAsnPheLeuLeuAsnCysProPheIle202530ValThrLeuAsnIle35(2) INFORMATION FOR SEQ ID NO:163:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 34 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:163:TyrAlaIlePheValLeuTyrAlaThrAlaTrpLeuPhePhePheLeu1 51015LeuPheGlyTyrLeuGlyAsnPheLeuLeuProPheIleValThrLeu202530AsnIle(2) INFORMATION FOR SEQ ID NO:164:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 45 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:164:TyrAlaIlePheValLeuTyrAlaThrAlaTrpLeuThrPheLeuAsn 151015ThrAlaCysPheTyrValAlaIleThrAlaSerLeuCysPheIleThr202530GluIleAlaLeuIleProPheIleValThrLeuAsnIle354045(2) INFORMATION FOR SEQ ID NO:165:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 42 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:165:TyrAlaIlePheValLeuTyrAlaThrAlaTrpLeuThrAlaCysPhe151015Tyr ValAlaIleThrAlaThrLeuCysPheIleThrGluIleAlaLeu202530IleCysProPheIleValThrLeuAsnIle35 40(2) INFORMATION FOR SEQ ID NO:166:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 42 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:166:TyrAlaIlePheValLeuTyrAlaThrAlaCysPheT yrValAlaIle151015ThrAlaThrLeuCysPheIleThrGluIleAlaLeuIleSerPheLeu2025 30AsnCysProPheIleValThrLeuAsnIle3540(2) INFORMATION FOR SEQ ID NO:167:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 42 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:167:TyrAlaIleThrAlaCysPheTyrValAlaIleThrAlaSerLeuCys151015PheIleThrGluIle AlaLeuIleAlaThrAlaTrpLeuThrPheLeu202530AsnCysProPheIleValThrLeuAsnIle3540(2) INFORMATION FOR SEQ ID NO:168:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 40 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:168:TyrAlaIlePheValLeuTyrAlaThrAlaCysPheTyrValAlaIle 151015IleThrGluIleAlaLeuIleThrAlaTrpLeuThrPheLeuAsnCys202530ProPheIleValThrLeuAsnIle3540(2) INFORMATION FOR SEQ ID NO:169:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 39 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:169:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuThrPheLeuAsn151015AlaCysPheTyrIleCysLeuPheAlaGlyVal CysPheLeuIlePro202530PheIleValThrLeuAsnIle35(2) INFORMATION FOR SEQ ID NO:170:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 41 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:170:TyrAlaIlePheValLeuTyrAlaSerAlaTrpAsnAlaCysPheTyr1510 15IleCysLeuPheAlaGlyValMetPheLeuIleLeuThrPheLeuAsn202530CysProPheIleValThrLeuAsnIle 3540(2) INFORMATION FOR SEQ ID NO:171:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 38 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:171:TyrAlaIlePheValLeuTyrPheT yrIleCysLeuPheAlaGlyVal151015CysPheLeuIleAlaThrAlaTrpLeuThrPheLeuAsnCysProPhe20 2530IleValThrLeuAsnIle35(2) INFORMATION FOR SEQ ID NO:172:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 34 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:172:TyrAlaIlePheValLeuTyrAlaThrValAspAlaValAsnMetPhe151015ThrThrAlaTrpLeuThrPheLeuAsnCys ProPheIleValThrLeu202530AsnIle(2) INFORMATION FOR SEQ ID NO:173:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 34 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single( D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:173:TyrAlaIlePheThrValAspAlaValAsnMetPheThrValLeuTyr151015AlaThrAlaTrpL euThrPheLeuAsnCysProPheIleValThrLeu202530AsnIle(2) INFORMATION FOR SEQ ID NO:174:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 34 amino acids(B) TYPE: amino acid (C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:174:TyrAlaIlePheValLeuTyrAlaThrAlaTrpLeuThrValAspAla151015 ValAsnMetPheThrSerPheLeuAsnCysProPheIleValThrLeu202530AsnIle(2) INFORMATION FOR SEQ ID NO:175:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 33 amino acids (B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:175:TyrAlaIlePheValLeuTyrAlaThrAlaTrpLeuSerPheLeuAsn1510 15ThrValAspAlaValAsnMetPheThrProPheIleValThrLeuAsn202530Ile(2) INFORMATION FOR SEQ ID NO:176:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 34 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:176:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuThrPheLeuAsn15 1015CysProPheIleValSerValAspAlaValAsnMetPheThrThrLeu202530AsnIle(2) INFORMATION FOR SEQ ID NO:177:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 31 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:177:TyrAlaIlePheValLeuTyrAlaThrAlaTrpLeuSerValAspMet 151015PheThrThrPheLeuAsnCysProPheIleValThrLeuAsnIle202530(2) INFORMATION FOR SEQ ID NO:178:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 34 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:178:TyrAlaIleSerValAspAlaValAsnMetPheThrPheValLeuTyr 151015AlaThrAlaTrpLeuSerPheLeuAsnCysProPheIleValThrLeu202530 AsnIle(2) INFORMATION FOR SEQ ID NO:179:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 35 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:179:TyrAlaIlePheValLeuTyrAlaSerLeuThrVal PheSerLeuLeu151015AlaIleSerAlaTrpLeuThrPheLeuAsnCysProPheIleValThr2025 30LeuAsnIle35(2) INFORMATION FOR SEQ ID NO:180:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 35 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:180:Tyr AlaIlePheValLeuTyrAlaSerAlaTrpLeuThrLeuSerVal151015PheThrLeuLeuAlaIleSerPheLeuAsnCysProPheIleValThr 202530LeuAsnIle35(2) INFORMATION FOR SEQ ID NO:181:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 35 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:181:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuThrPheLeuSer151015LeuSerValPheThrL euLeuAlaIleAsnCysProPheIleValThr202530LeuAsnIle35(2) INFORMATION FOR SEQ ID NO:182:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 34 amino acids (B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:182:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuThrPheLeuAsn1510 15ProPheSerLeuSerValPheSerLeuLeuAlaIleIleValThrLeu202530AsnIle(2) INFORMATION FOR SEQ ID NO:183:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 37 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:183:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn15 1015LeuGlyGlyValThrAlaSerPheThrAlaSerValGlyProPheIle202530ValThrLeuAsnIle 35(2) INFORMATION FOR SEQ ID NO:184:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 34 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:184:TyrAlaIlePheValLeuTyrAlaSerAlaT rpLeuSerPheLeuAsn151015LeuGlyGlyValThrAlaSerPheThrAlaSerValGlyValThrLeu20 2530AsnIle(2) INFORMATION FOR SEQ ID NO:185:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 38 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:185:TyrAlaIlePheVal LeuLeuGlyGlyValThrAlaSerPheThrAla151015SerValAsnTyrAlaSerAlaTrpLeuSerPheLeuAsnCysProPhe 202530IleValThrLeuAsnIle35(2) INFORMATION FOR SEQ ID NO:186:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 32 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:186:TyrAlaIlePheValLeuTyrAlaIlePhePhePheLeuLeuPheSer151015AlaTrpLeuSerPheLeuA snCysProPheIleValThrLeuAsnIle202530(2) INFORMATION FOR SEQ ID NO:187:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 38 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:187:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn151015CysProPheIleVal ThrLeuAsnIleIlePhePhePheLeuLeuPhe202530IleValThrLeuAsnIle35(2) INFORMATION FOR SEQ ID NO:188:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 32 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:188:TyrAlaIlePheValLeuTyrAlaSerAlaTrpIlePhePhePheLeu15 1015LeuPheLeuSerPheLeuAsnCysProPheIleValThrLeuAsnIle202530(2) INFORMATION FOR SEQ ID NO:189:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 41 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:189:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuPhePheThrVal15 1015LeuAlaSerGluLeuSerValTyrThrLeuThrValSerPheLeuAsn202530CysProPheIleValThr LeuAsnIle3540(2) INFORMATION FOR SEQ ID NO:190:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 34 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:190:TyrAla IlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuPhe151015AlaThrLeuGlyGlyGluIleAlaLeuCysProPheIleValThrLeu 202530AsnIle(2) INFORMATION FOR SEQ ID NO:191:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 35 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi ) SEQUENCE DESCRIPTION: SEQ ID NO:191:TyrAlaIlePheValLeuTyrAlaPheAlaThrLeuGlyGlyGluIle151015AlaLeuSerAlaTrpLeuSerPheLeuAsnCysPro PheIleValThr202530LeuAsnIle35(2) INFORMATION FOR SEQ ID NO:192:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 38 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:192:TyrAlaIlePhePheThrValLeuAlaSerGluLeuSerValTyrThr151015Leu ThrValTyrAlaSerAlaTrpLeuSerPheLeuAsnCysProPhe202530IleValThrLeuAsnIle35(2) INFORMATION FOR SEQ ID NO:193:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 32 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:193:TyrAlaIlePhePheProIleAlaAlaLeuPheAlaSerIleAlaSer1 51015AlaTrpLeuSerPheLeuAsnCysProPheIleValThrLeuAsnIle202530(2) INFORMATION FOR SEQ ID NO:194: (i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 32 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:194:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPhePhePro1 51015IleAlaAlaLeuPheAlaSerIleProPheIleValThrLeuAsnIle202530(2) INFORMATION FOR SEQ ID NO:195: (i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 32 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:195:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn1 51015CysProPhePheProIleAlaAlaLeuPheAlaSerIleLeuAsnIle202530(2) INFORMATION FOR SEQ ID NO:196:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 45 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:196:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerLeuAspVal 151015LeuPheSerThrAlaSerIleMetHisLeuSerPheLeuAsnGlyGly202530 GluIleAlaLeuTrpSerLeuIleValThrLeuAsnIle354045(2) INFORMATION FOR SEQ ID NO:197:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 38 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single (D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:197:TyrAlaIlePheValLeuTyrAlaSerLeuAspValLeuPheSerThr151015AlaS erIleMetHisLeuIleAlaLeuTrpSerLeuAsnCysProPhe202530IleValThrLeuAsnIle35(2) INFORMATION FOR SEQ ID NO:198:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 43 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:198:TyrAlaIlePheValLeuTyrAlaGlyGlyGluIleAlaLeuTrpSer1 51015LeuSerPheLeuAsnSerLeuAspValLeuPheSerThrAlaSerIle202530MetHisLeuPro PheIleValThrLeuAsnIle3540(2) INFORMATION FOR SEQ ID NO:199:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 46 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:199:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPhePheAsp151015ValLeuPheSerThrAlaSerIleMetHisLeuPheGlyT yrLeuGly202530AsnPheLeuLeuAsnCysProPheIleValThrLeuAsnIle354045( 2) INFORMATION FOR SEQ ID NO:200:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 48 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:200:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuPhePhePheLeu151015LeuPheGlyTyrLeuSerLeuAspValLeuPheSerThrAlaSerIle202530MetHisLeuGlyAsnPheLeuLeuProPheIleValThrLeuAsnIle354045(2) INFORMATION FOR SEQ ID NO:201:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 49 amino acids(B) TYPE: amino acid (C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:201:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn1510 15ThrAlaCysPheTyrValAlaIleThrAlaSerLeuSerLeuMetHis202530LeuPheIleThrGluIleAlaLeuIleProPheIleValThr LeuAsn354045Ile(2) INFORMATION FOR SEQ ID NO:202:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 49 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:202:TyrAlaSerLeuAspValLeuPheSerThrAlaIleMetHisLeuSer151015AlaTrpLeuThrAlaCysPheTyrValAlaI leThrAlaSerLeuCys202530PheIleThrGluIleAlaLeuIleCysProPheIleValThrLeuAsn3540 45Ile(2) INFORMATION FOR SEQ ID NO:203:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 47 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:203:TyrAlaIlePheValLeuTyrAla ThrAlaCysPheTyrValAlaIle151015ThrAlaSerLeuSerPheLeuAsnCysProPheIleValThrLeuAsn20 2530IleSerLeuAspValLeuPheSerThrAlaSerIleMetHisLeu354045(2) INFORMATION FOR SEQ ID NO:204:(i) SEQUENCE CHARACTERISTICS:(A ) LENGTH: 42 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:204:TyrAlaIleThrAlaCysPheTyrValAlaIleThrAlaSerLeuCys15 1015PheIleThrGluIleAlaLeuIleAlaSerAlaTrpLeuSerPheLeu202530AsnCysProPheIleValThr LeuAsnIle3540(2) INFORMATION FOR SEQ ID NO:205:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 48 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:205:TyrAla IlePheValLeuTyrAlaThrAlaCysPheTyrSerThrAla151015SerIleLeuAsnLeuIleMetHisLeuCysAlaIleSerLeuValAla 202530IleIleThrGluIleAlaLeuIleSerAlaTrpLeuSerPheLeuAsn354045(2) INFORMATION FOR SEQ ID NO:206:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 48 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:206:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn 151015AlaCysPheTyrIleCysLeuPheAlaSerIleLeuAsnLeuIleMet202530 HisLeuGlyValCysPheLeuIleProPheIleValThrLeuAsnIle354045(2) INFORMATION FOR SEQ ID NO:207:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 49 amino acids(B) TYPE: amino acid (C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:207:TyrAlaIlePheValLeuTyrAlaSerAlaTrpAsnAlaSerIleLeu151015 AsnLeuIleMetHisLeuCysPheTyrIleCysLeuPheAlaGlyVal202530MetLeuIleLeuSerPheLeuAsnCysProPheIleValThrLeuAsn354045Ile(2) INFORMATION FOR SEQ ID NO:208:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 50 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:208:TyrAlaIlePheProPheValGlnCysValValSerIlePheSerLeu151015ValLeuIleAlaValValLeuTyrPheTyrIleAlaG lyValCysPhe202530LeuIleAlaSerAlaTrpLeuSerPheLeuAsnCysProPheIleVal3540 45ThrIle50(2) INFORMATION FOR SEQ ID NO:209:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 49 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:209:ProPheValGlnCysV alSerIleThrValSerIlePheSerLeuVal151015LeuIleAlaValTyrAlaIlePheValLeuTyrAlaSerValAspAla 202530ValAsnMetPheThrSerAlaTrpCysProPheIleValThrLeuAsn354045Ile(2) INFORMATION FOR SEQ ID NO:210: (i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 38 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:210:TyrAlaIlePheGlyAspTrpSerSerValAspAlaValAsnMetPhe1 51015ThrValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsnCysProPhe202530I leValThrLeuAsnIle35(2) INFORMATION FOR SEQ ID NO:211:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 38 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:211:TyrAlaIlePheV alLeuTyrAlaGlyAspTrpSerSerAlaTrpLeu151015SerValAspAlaValAsnMetPheThrSerPheLeuAsnCysProPhe 202530IleValThrLeuAsnIle35(2) INFORMATION FOR SEQ ID NO:212:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 37 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:212:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuGlyAspTrpSer151015SerPheLeuAsnSerVal AspAlaValAsnMetPheThrProPheIle202530ValThrLeuAsnIle35(2) INFORMATION FOR SEQ ID NO:213:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 38 amino acids (B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:213:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn1510 15CysProPheIleValGlyAspTrpSerSerValAspAlaValAsnMet202530PheThrThrLeuAsnIle 35(2) INFORMATION FOR SEQ ID NO:214:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 39 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:214:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuGlyT yrLeuGly151015SerValAspMetPheThrSerPheLeuAsnCysProPheIleValThr2025 30GlyAspTrpSerLeuAsnIle35(2) INFORMATION FOR SEQ ID NO:215:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 38 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:215:TyrAlaIleSerValAspAlaValAsnMetPheThrPheValLeuTyr151015AlaGlyTyrLeuGlySerAlaTrpLeuSerPheLeuAsnCys ProPhe202530IleValThrLeuAsnIle35(2) INFORMATION FOR SEQ ID NO:216:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 39 amino acids(B) TYPE: amino acid( C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:216:TyrAlaIlePheSerLeuSerValPheSerLeuLeuAlaIleValLeu151015 TyrAlaSerAlaTrpLeuGlyTyrLeuGlySerPheLeuAsnCysPro202530PheIleValThrLeuAsnIle35(2) INFORMATION FOR SEQ ID NO:217: (i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 44 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:217:TyrAlaIlePheValLeuTyrAlaGlyTyrLeuGlyAlaGlyAsnMet1 51015AspSerLeuSerValPheSerLeuLeuAlaIleSerAlaTrpLeuSer202530PheL euAsnCysProPheIleValThrLeuAsnIle3540(2) INFORMATION FOR SEQ ID NO:218:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 38 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:218:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerLeuSerVal151015PheGlyAsnMetSerLeuLeuAlaIleSer PheLeuAsnCysProPhe202530IleValThrLeuAsnIle35(2) INFORMATION FOR SEQ ID NO:219:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 37 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:219:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuSer1510 15LeuSerValPheGlyGlySerLeuLeuAlaIleAsnCysProPheIle202530ValThrLeuAsnIle35(2) INFORMATION FOR SEQ ID NO:220:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 35 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:220:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn 151015ProPheSerLeuSerValPheGlySerLeuLeuAlaIleIleValThr202530 LeuAsnIle35(2) INFORMATION FOR SEQ ID NO:221:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 33 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:221:TyrAlaIlePheValLeuT yrAlaThrAlaTrpLeuThrPheLeuSer151015LeuAlaAsnCysValThrAlaThrIleProPheIleValThrLeuAsn20 2530Ile(2) INFORMATION FOR SEQ ID NO:222:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 35 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:222:TyrAla IlePheValLeuTyrAlaThrAlaTrpLeuSerPheLeuAsn151015CysThrSerLeuAlaSerSerIleValValThrAlaThrIleValThr 202530LeuAsnIle35(2) INFORMATION FOR SEQ ID NO:223:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 30 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:223:TyrAlaIlePheValLeuTyrAlaThrAlaTrpLeuSerPheLeuAsn151015ValThrLeuAsnIleSerL euAlaCysThrThrThrIleVal202530(2) INFORMATION FOR SEQ ID NO:224:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 34 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:224:TyrAlaIlePheValLeuTyrAlaThrAlaTrpLeuThrPheLeuAsn151015ThrAlaThrIleLeuSerLeu AlaAsnLeuMetPheIleValThrLeu202530AsnIle(2) INFORMATION FOR SEQ ID NO:225:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 36 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single (D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:225:TyrAlaIlePheValLeuTyrAlaThrAlaTrpLeuSerPheLeuAsn151015MetA laThrIleLeuAsnLeuProPheSerValAspAlaValIleVal202530ThrLeuAsnIle35(2) INFORMATION FOR SEQ ID NO:226:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 41 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:226:IleSerThrMetTyrThrValThrGlyArgTrpThrLeuGlyGlnVal15 1015ValCysAspPheTrpLeuSerSerAspIleThrCysCysThrAlaSer202530IleLeuHisLeuCysVal IleAlaLeu3540(2) INFORMATION FOR SEQ ID NO:227:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 37 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:227:IleLeu TyrGlyTyrArgTrpProLeuProSerLysLeuCysAlaVal151015TrpIleTyrLeuAspValLeuPheSerThrAlaSerIleMetHisLeu 202530CysAlaIleSerLeu35(2) INFORMATION FOR SEQ ID NO:228:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 39 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single( D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:228:IleIleTyrIleValMetAspArgTrpLysLeuGlyTyrPheLeuCys151015GluValTrpLeuS erValAspMetThrCysCysThrCysSerIleLeu202530HisLeuCysValIleAlaLeu35(2) INFORMATION FOR SEQ ID NO:229:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 36 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:229:IleAlaAspLysThrValArgValAlaMetGlyAlaGluAsnAspLeu15 1015GlyTyrAsnPheArgSerAspAspValCysGlyHisCysTrpGlnTrp202530TyrCysSerLeu 35(2) INFORMATION FOR SEQ ID NO:230:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 35 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:230:IleLeuAsnTyrTrpProPheGlyLeuAlaLeuCys HisPheValAsn151015TyrSerGlnAlaValSerValLeuValSerAlaTyrThrLeuValAla2025 30IleSerIle35(2) INFORMATION FOR SEQ ID NO:231:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 36 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:231:Ile LeuGlyArgTrpGluPheGlyIleHisLeuCysLysLeuTrpLeu151015ThrCysAspValLeuCysCysThrSerSerIleLeuAsnLeuCysAla 202530IleAlaLeuAsp35(2) INFORMATION FOR SEQ ID NO:232:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 35 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single( D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:232:IleMetAlaSerValMetHisArgHisCysLeuProLeuIleGlyIle151015CysLeuSerSerG luArgHisCysLeuValSerIlePheValGluLeu202530GlyAlaLeu35(2) INFORMATION FOR SEQ ID NO:233:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 35 amino acids (B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:233:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn1510 15CysProPheIleSerIleLeuHisLeuCysValIleAlaLeuValThr202530LeuAsnIle35(2) INFORMATION FOR SEQ ID NO:234:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 36 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:234:TyrAlaIlePheValLeuTyrAlaThrAlaTrpLeuSerPheLeuAsn 151015CysProPheIleSerIleLeuAsnLeuCysAlaIleAlaLeuAspVal202530 ThrLeuAsnIle35(2) INFORMATION FOR SEQ ID NO:235:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 34 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:235:TyrAlaIlePheVal LeuTyrAlaThrAlaTrpLeuThrPheLeuAsn151015CysProPheIleSerIlePheValGluLeuGlyAlaLeuValThrLeu 202530AsnIle(2) INFORMATION FOR SEQ ID NO:236:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 44 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:236: TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuThrPheLeuAsn151015CysProPheIleSerIlePheValGluLeuSerIleMetHisLeu Cys202530AlaIleSerLeuGlyAlaLeuValThrLeuAsnIle3540(2) INFORMATION FOR SEQ ID NO:237:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 52 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:237:TrpAlaIlePheValLeuTyrAlaIleLeuGlyArgTrpGluPheGly15 1015IleHisLeuCysLysLeuTrpLeuThrSerAlaTrpLeuSerIleMet202530HisLeuCysAlaIleSerL euSerPheLeuAsnCysProPheIleVal354045ThrLeuAsnIle50(2) INFORMATION FOR SEQ ID NO:238:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 52 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:238:TrpAlaIlePheValLeuTyrAlaIleLeuGlyArgTrpGluPheGly1510 15IleHisLeuCysLysLeuTrpLeuThrThrAlaTrpLeuSerIleMet202530HisLeuCysAlaIleSerLeuSerPheLeuAsnCysPro PheIleVal354045ThrLeuAsnIle50(2) INFORMATION FOR SEQ ID NO:239:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 35 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single (D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:239:TrpAlaIlePheValLeuTyrAlaThrAlaTrpLeuThrPheLeuAsn151015CysProPhe SerIleMetHisLeuCysAlaIleSerLeuIleValThr202530LeuAsnIle35(2) INFORMATION FOR SEQ ID NO:240:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 35 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:240:TrpAlaIlePheValLeuTyrAlaSerAlaTrpLeuThrPheLeuAsn15 1015CysProPheIleSerIleMetHisLeuCysAlaIleSerLeuValThr202530LeuAsnIle35 (2) INFORMATION FOR SEQ ID NO:241:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 35 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:241:TyrAlaValPheValLeuTyrAlaSerAlaTrpLeuSerPheLeuA sn151015MetSerIleMetHisLeuCysAlaIleSerLeuProPheIleValThr2025 30LeuAsnIle35(2) INFORMATION FOR SEQ ID NO:242:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 36 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:242:TyrAlaValPheV alLeuTyrAlaThrAlaTrpLeuSerPheLeuAsn151015MetProPheSerIleLeuAsnLeuCysAlaIleAlaLeuAspIleVal 202530ThrLeuAsnIle35(2) INFORMATION FOR SEQ ID NO:243:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 36 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(i i) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:243:TyrAlaValPheValLeuTyrAlaThrAlaTrpLeuSerIleLeuAsn151015LeuCysAlaIleAlaLeuAspThr PheLeuAsnMetProPheIleVal202530ThrLeuAsnIle35(2) INFORMATION FOR SEQ ID NO:244:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 36 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:244:TyrAlaValPheValLeuTyrAlaSerIleLeuAsnLeuCysAlaIle1510 15AlaLeuAspSerAlaTrpLeuThrPheLeuAsnMetProPheIleVal202530ThrLeuAsnIle35(2) INFORMATION FOR SEQ ID NO:245: (i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 42 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:245:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn1 51015CysValThrAlaSerIleProPheCysLeuValSerIlePheValGlu202530L euGlyAlaLeuIleValThrLeuAsnIle3540(2) INFORMATION FOR SEQ ID NO:246:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 40 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:246:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn151015CysLeuValSerIlePheValGluLeuGlyAla LeuIleValValThr202530AlaSerIleValThrLeuAsnIle3540(2) INFORMATION FOR SEQ ID NO:247:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 34 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:247:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn15 1015ValThrLeuAsnCysLeuValSerIlePheValGluLeuGlyAlaLeu202530IleIle(2) INFORMATION FOR SEQ ID NO:248: (i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 43 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:248:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn1 51015ThrAlaSerIleLeuAsnLeuMetPheIleCysLeuValSerIlePhe202530Val GluLeuGlyAlaLeuValThrLeuAsnIle3540(2) INFORMATION FOR SEQ ID NO:249:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 42 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:249:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn151015MetAlaSerIleLeuAsnLeuProPheCysL euValSerIlePheVal202530GluLeuGlyAlaLeuValThrLeuAsnIle3540(2) INFORMATION FOR SEQ ID NO:250:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 56 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:250:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn1 51015IleLeuGlyArgTrpGluPheGlyIleHisLeuCysLysLeuTrpLeu202530ThrCysAspVal LeuCysCysThrSerSerGlyIleLeuLeuLeuAla354045ProPheIleValThrLeuAsnIle5055(2) INFORMATION FOR SEQ ID NO:251: (i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 57 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:251:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn1 51015MetIleLeuGlyArgTrpGluPheGlyIleHisLeuCysLysLeuTrp202530LeuT hrCysAspValLeuCysCysThrSerSerGlyIleLeuLeuLeu354045AlaProPheIleValThrLeuAsnIle5055( 2) INFORMATION FOR SEQ ID NO:252:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 60 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:252:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuIleLeuGlyArg151015TrpGluPheGlyIleHisLeuCysLysLeuTrpLeuThrCysAspVal202530LeuCysCysThrSerSerPheLeuAsnSerGluLeuSerValTyrThr354045LeuThrValCysProPheIleValThrLeuAsnIle50 5560(2) INFORMATION FOR SEQ ID NO:253:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 60 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:253:TyrAlaIlePheV alLeuTyrAlaIleLeuGlyArgTrpGluPheGly151015IleHisLeuCysLysLeuTrpLeuThrCysAspValLeuCysCysThr 202530SerSerAlaTrpLeuSerPheLeuAsnMetSerGluLeuSerValTyr354045ThrLeuThrVal ProPheIleValThrLeuAsnIle505560(2) INFORMATION FOR SEQ ID NO:254:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 40 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:254:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuAlaSerArgTrp151015ProLeuProLeuSerValTyrThrL euThrValSerPheLeuAsnCys202530ProPheIleValThrLeuAsnIle3540(2) INFORMATION FOR SEQ ID NO:255:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 62 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:255:TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuAlaSerGluLeu1 51015IleLeuTyrTyrTrpArgTrpProLeuProCysLeuHisAspLeuVal202530TrpLeuCysThr CysSerIleLeuHisLeuCysValIleAlaLeuSer354045ValTyrThrLeuThrValProPheIleValThrLeuAsnIle50 5560(2) INFORMATION FOR SEQ ID NO:256:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 59 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:256:TyrAlaIlePheValLeuTyrAlaS erAlaTrpLeuSerPheLeuAla151015SerGluLeuSerValTyrAlaSerGluLeuSerSerThrLeuHisAsp20 2530LeuValTrpLeuTrpLeuAspValPheCysValIleAlaLeuThrThr354045ValAsnMetProPheIleValThr LeuAsnIle5055(2) INFORMATION FOR SEQ ID NO:257:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 60 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:257:TyrAlaIle PheValLeuTyrAlaSerAlaTrpLeuSerPheLeuAsn151015GlyGlyGluIleAlaLeuTrpSerLeuCysProPheIleIleLeuTyr 202530TyrTrpArgTrpProLeuProCysLeuHisAspLeuValSerIleLeu354045HisLeuC ysValIleAlaLeuValThrLeuAsnIle505560(2) INFORMATION FOR SEQ ID NO:258:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 51 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:258:TyrValTrpLeuTrpLeuAspValPheCysCysThrCysSerIleLeu151015HisLeuCysValIleAlaLeu PheValLeuTyrAlaSerAlaTrpLeu202530SerPheLeuAsnGlyGlyGluIleAlaLeuTrpSerLeuIleValThr35 4045LeuAsnIle50(2) INFORMATION FOR SEQ ID NO:259:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 48 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:259: TyrAlaIlePheValLeuTyrAlaSerAlaTrpLeuAlaIleIleLeu151015TyrTyrTrpArgTrpProLeuProCysLeuHisAspLeuGlyG lyGlu202530IleAlaLeuTrpSerLeuAsnCysProPheIleValThrLeuAsnIle354045(2) INFORMATION FOR SEQ ID NO:260:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 25 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:260:CysAspValPheValPheValAspIleMetLeuCysThrAlaSer Ile151015PheAsnLeuCysAlaIleSerValGly2025(2) INFORMATION FOR SEQ ID NO:261:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 25 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:261:TyrAlaIlePheValLeuTyrAspIleMetLeuCysThrAlaSerIle15 1015PheAsnLeuCysAlaIleSerValGly2025(2) INFORMATION FOR SEQ ID NO:262:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 26 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single (D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:262:AspTyrAlaIlePheValPheValAspIleMetLeuMetThrAlaSer151015IleP heAsnLeuMetAlaIleSerValGly2025(2) INFORMATION FOR SEQ ID NO:263:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 29 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:263:AspTyrAlaIlePheValPheValAspIleMetLeuHisThrThrAla151015SerThrIlePheAsnLeuMetAlaThrIleThr ValGly2025(2) INFORMATION FOR SEQ ID NO:264:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 33 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:264:CysAsp ValAlaValValTyrSerSerAspIleMetLeuPheTyrVal151015CysThrAlaSerIlePheSerSerAsnLeuCysAlaIleSerSerVal 202530Gly(2) INFORMATION FOR SEQ ID NO:265:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 36 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:265:PheLeuPheCysSerLeuGlySerPheTyrIleProIleAlaValIle151015LeuValAspIleMetLeuCysThrAlaSerIlePheAsn LeuCysAla202530IleSerValGly35(2) INFORMATION FOR SEQ ID NO:266:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 42 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:266:TyrAlaIlePheValLeuTyrAspPheLeuPheCysSerLeuGlySer151015Phe TyrIleProIleAlaValIleLeuIleMetLeuCysThrAlaSer202530IlePheAsnLeuCysAlaIleSerValGly35 40(2) INFORMATION FOR SEQ ID NO:267:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 38 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:267:AspTyrAlaIlePheValPheValAspIleMetLeuM etThrAlaSer151015IlePheLeuPheCysSerLeuGlySerPheTyrIleProIleAlaVal2025 30IleLeuIleSerValGly35(2) INFORMATION FOR SEQ ID NO:268:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 46 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:268:AspTyrAlaIlePheValPheValAspIleMetLeuHisThrThrAla151015SerThrIlePheAsnLeuMetAlaPheLeuPheCysSerLeu GlySer202530PheTyrIleProIleAlaValIleLeuThrIleThrValGly354045(2) INFORMATION FOR SEQ ID NO:269:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 43 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:269:CysAspValAlaValValTyrSerSerAspIleMetLeuPheTyrVal 151015CysThrAlaSerIlePheSerSerAsnLeuPheLeuPheCysSerLeu202530GlySerPheTyrCysAlaIleSerSerValGly3540(2) INFORMATION FOR SEQ ID NO:270:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 46 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(i i) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:270:CysAspValPheValPheValAspIleMetLeuCysThrAlaSerIle151015PheAsnTrpTyrIleLeuSerSer IleGlySerPhePheAlaProCys202530LeuIleLeuLeuValTyrLeuLeuCysAlaIleSerValGly3540 45(2) INFORMATION FOR SEQ ID NO:271:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 46 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:271:TyrAlaIlePheValLeuTyrAspIleMetL euCysThrAlaSerIle151015PheAsnLeuCysAlaIleTrpTyrIleLeuSerSerIleGlySerPhe20 2530PheAlaProCysLeuIleLeuLeuValTyrLeuSerValGly354045(2) INFORMATION FOR SEQ ID NO:272:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 43 amino acids (B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:272:AspTyrAlaIlePheValPheValAspIleTrpTyrIleLeuSerSer1510 15IleGlySerPhePheAlaProCysLeuIleLeuLeuValTyrLeuAla202530SerIlePheAsnLeuMetAlaIleSerValG ly3540(2) INFORMATION FOR SEQ ID NO:273:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 45 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:273:AspTyrAlaIleT rpTyrIleLeuSerSerIleGlySerPhePheAla151015ProCysLeuIleLeuLeuValTyrLeuIleMetLeuHisThrThrAla 202530SerThrIlePheAsnLeuMetAlaThrIleThrValGly354045(2) INFORMATION FOR SEQ ID NO:274:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 49 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:274:CysAspValAlaValValTyrSerSerAspIleMetLeuPheTyrVal15 1015CysTrpTyrIleLeuSerSerIleGlySerPhePheAlaProCysLeu202530IleLeuLeuValTyrL euSerSerAsnLeuCysAlaIleSerSerVal354045Gly(2) INFORMATION FOR SEQ ID NO:275:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 47 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single (D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:275:CysAspValPheValPheValAspIleMetLeuCysThrAlaSerIle151015PheTrp TyrValIleSerSerSerIleGlySerPhePheAlaProCys202530LeuIleAsnHisLeuValTyrAsnLeuCysAlaIleSerValGly 354045(2) INFORMATION FOR SEQ ID NO:276:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 47 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:276:TyrAlaIleP heValLeuTyrAspIleMetLeuCysThrAlaSerIle151015PheAsnLeuCysAlaIleTrpTyrValIleSerSerSerIleGlySer 202530PhePheAlaProCysLeuIleAsnHisLeuValTyrSerValGly354045(2) INFORMATION FOR SEQ ID NO:277:(i ) SEQUENCE CHARACTERISTICS:(A) LENGTH: 48 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:277:AspTyrAlaIlePheValPheValTrpTyrValIleSerSerSerIle1 51015GlySerPhePheAlaProCysLeuIleAsnHisLeuValTyrAspIle202530MetLeuM etThrAlaSerIlePheAsnLeuMetAlaIleSerValGly354045(2) INFORMATION FOR SEQ ID NO:278:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 45 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single (D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:278:AspTyrAlaIlePheValPheValAspIleMetLeuHisThrThrAla151015SerThr IlePheTrpTyrValIleSerSerSerIleGlySerPhePhe202530AlaProCysLeuIleAsnHisLeuValTyrThrValGly35 4045(2) INFORMATION FOR SEQ ID NO:279:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 49 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:279:CysAspValAlaValV alTyrSerSerAspIleMetLeuPheTyrVal151015CysThrAlaSerIlePheSerTrpTyrValIleSerIleGlySerPhe 202530PheAlaIleAsnHisLeuValTyrAsnLeuCysAlaIleSerSerVal354045Gly(2) INFORMATION FOR SEQ ID NO:280: (i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 44 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:280:CysAspValPheValPheValAspIleMetLeuCysThrAlaSerIle1 51015PheAsnLeuCysAlaIleThrTyrAlaIleSerSerSerValIleSer202530P heTyrIleProValAlaIleLeuValThrTyrThr3540(2) INFORMATION FOR SEQ ID NO:281:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 47 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:281:TyrAlaIlePheValLeuTyrAspIleMetLeuCysThrAlaThrTyr151015AlaIleSerSerSerValIleSerPhe TyrIleProValAlaIleLeu202530ValThrTyrThrSerIlePheAsnLeuCysAlaIleSerValGly3540 45(2) INFORMATION FOR SEQ ID NO:282:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 41 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:282:AspTyrAlaIlePheValPheValAspIleM etLeuMetThrAlaThr151015TyrAlaIleSerSerSerValIleSerPheTyrIleProValAlaIle20 2530LeuValThrTyrThrIleSerValGly3540(2) INFORMATION FOR SEQ ID NO:283:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 46 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single (D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:283:ThrTyrAlaIleSerSerSerValIleSerPheTyrIleProValAla151015ThrAspTyrAla IlePheValPheValAspIleMetLeuHisThrThr202530AlaSerThrIlePheAsnLeuMetAlaThrIleThrValGly35 4045(2) INFORMATION FOR SEQ ID NO:284:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 45 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:284:CysAspValAlaValValT yrSerSerAspIleMetLeuPheTyrVal151015CysThrAlaThrTyrAlaIleSerSerSerValIleSerPheTyrIle20 2530ProValAlaIleLeuValThrTyrThrSerSerValGly354045(2) INFORMATION FOR SEQ ID NO:285:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 44 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:285:CysAspValPheValPheValAspPheValIleTyrSerSerValVal15 1015SerPheTyrLeuProPheGlyValThrValLeuValTyrAlaCysThr202530AlaSerIlePheAsnLeuCysA laIleSerValGly3540(2) INFORMATION FOR SEQ ID NO:286:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 41 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:286:T yrAlaIlePheValLeuTyrAspPheValIleTyrSerSerValVal151015SerPheTyrLeuProPheGlyValThrValLeuValTyrAlaSerIle202530PheAsnLeuCysAlaIleSerValGly3540(2) INFORMATION FOR SEQ ID NO:287:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 44 amino acids (B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:287:AspTyrAlaIlePheValPheValAspPheValIleTyrSerSerVal1510 15ValSerPheTyrLeuProPheGlyValThrValLeuValTyrAlaThr202530AlaSerIlePheAsnLeuMetAlaIleSerV alGly3540(2) INFORMATION FOR SEQ ID NO:288:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 48 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:288:AspTyrAlaI lePheValPheValAspPheValIleTyrSerSerVal151015ValSerPheTyrLeuProPheGlyValThrValLeuValTyrAlaHis 202530ThrThrAlaSerThrIlePheAsnLeuMetAlaThrIleThrValGly354045(2) INFORMATION FOR SEQ ID NO:289: (i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 47 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:289:CysAspValAlaValValTyrSerSerAspPheValIleTyrSerSer1 51015ValValSerPheTyrLeuProPheGlyValThrValTyrValCysThr202530AlaS erIlePheSerSerAsnLeuCysAlaIleSerSerValGly354045(2) INFORMATION FOR SEQ ID NO:290:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 45 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single (D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:290:CysAspValPheValPheValAspIleMetLeuCysThrAlaSerTyr151015ThrIle TyrSerThrCysGlyAlaPheTyrIleProSerValLeuLeu202530IleIleLeuTyrGlyAsnLeuCysAlaIleSerValGly35 4045(2) INFORMATION FOR SEQ ID NO:291:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 45 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:291:TyrAlaIlePheValL euTyrAspIleMetLeuCysThrAlaSerTyr151015ThrIleTyrSerThrCysGlyAlaPheTyrIleProSerValLeuLeu 202530IleIleLeuTyrGlyAsnLeuCysAlaIleSerValGly354045(2) INFORMATION FOR SEQ ID NO:292:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 46 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:292:AspTyrAlaIlePheValPheValAspIleMetLeuMetThrAlaSer15 1015TyrThrIleTyrSerThrCysGlyAlaPheTyrIleProSerValLeu202530LeuIleIleLeuTyrGlyA snLeuMetAlaIleSerValGly354045(2) INFORMATION FOR SEQ ID NO:293:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 46 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(i i) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:293:AspTyrAlaIlePheValPheValAspIleMetLeuHisThrThrAla151015SerTyrThrIleTyrSerThrCys GlyAlaPheTyrIleProSerVal202530LeuLeuIleIleLeuTyrGlyMetAlaThrIleThrValGly3540 45(2) INFORMATION FOR SEQ ID NO:294:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 48 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:294:CysAspValAlaValValTyrSerSerAspI leMetSerTyrThrIle151015TyrSerThrCysGlyAlaPheTyrIleProSerValLeuLeuIleIle20 2530LeuTyrGlyIlePheSerSerAsnLeuCysAlaIleSerSerValGly354045(2) INFORMATION FOR SEQ ID NO:295:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 34 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:295:CysAspValPheValPhePheValLeuIleGlySerPheValAlaVal15 1015AspIleMetLeuCysThrAlaSerIlePheAsnLeuCysAlaIleSer202530ValGly(2) INFORMATION FOR SEQ ID NO:296:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 34 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:296:TyrAlaIlePheValLeuTyrPheValLeuIleGlySerPheValAla1 51015AspIleMetLeuCysThrAlaSerIlePheAsnLeuCysAlaIleSer202530ValGly (2) INFORMATION FOR SEQ ID NO:297:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 35 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:297:AspTyrAlaIlePheValPheValPheValLeuIleGlySerPheV al151015AlaAspIleMetLeuMetThrAlaSerIlePheAsnLeuMetAlaIle2025 30SerValGly35(2) INFORMATION FOR SEQ ID NO:298:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 38 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:298:AspTyrAlaIleP heValPheValPheValLeuIleGlySerPheVal151015AlaAspIleMetLeuHisThrThrAlaSerThrIlePheAsnLeuMet 202530AlaThrIleThrValGly35(2) INFORMATION FOR SEQ ID NO:299:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 42 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:299:CysAspValAlaValValTyrSerSerPheValLeuIleGlySerPhe151015ValAlaAspIleMetLeu PheTyrValCysThrAlaSerIlePheSer202530SerAsnLeuCysAlaIleSerSerValGly3540(2) INFORMATION FOR SEQ ID NO:300:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 33 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:300:CysAspValPheValPheValAspIleMetLeuCysPhePheIlePro 151015ThrLeuIleMetValIleThrTyrPheAsnLeuCysAlaIleSerVal202530 Gly(2) INFORMATION FOR SEQ ID NO:301:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 34 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:301:TyrAlaIlePheValLeuTyrAspIleMetLeuCysPhe PheIlePro151015ThrLeuIleMetValIleThrTyrPhePheAsnLeuCysAlaIleSer2025 30ValGly(2) INFORMATION FOR SEQ ID NO:302:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 34 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:302:AspTyrAlaIlePheValPheV alAspIleMetLeuMetPhePheIle151015ProThrLeuIleMetValIleThrTyrPheAsnLeuMetAlaIleSer20 2530ValGly(2) INFORMATION FOR SEQ ID NO:303:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 36 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:303:AspTyr AlaIlePheValPheValAspIleMetLeuHisThrPhePhe151015IleProThrLeuIleMetValIleThrTyrPheAsnLeuMetAlaThr 202530IleThrValGly35(2) INFORMATION FOR SEQ ID NO:304:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 41 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:304:CysAspValAlaValValTyrSerSerAspIleMetLeuPheTyrVal151015CysPhePheIleProT hrLeuIleMetValIleThrTyrPheSerSer202530AsnLeuCysAlaIleSerSerValGly3540(2) INFORMATION FOR SEQ ID NO:305:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 44 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:305:CysAspValValTyrGlyLeuValAspGlyLeuValThrPheTyrLeu 151015ProLeuLeuIleMetCysIleThrTyrTyrAspIleMetLeuCysThr202530 AlaSerIlePheAsnLeuCysAlaIleSerValGly3540(2) INFORMATION FOR SEQ ID NO:306:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 44 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:306:TyrAlaIleValTyrGlyLeuValAspGlyLeuValThrPheTyrLeu151015ProLeuLeuIleMetCysIleThrT yrTyrAspIleMetLeuCysThr202530AlaSerIlePheAsnLeuCysAlaIleSerValGly3540(2) INFORMATION FOR SEQ ID NO:307:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 45 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:307:AspTyrAlaIleValTyrGlyLeuValAspGlyLeuValThrPheTyr 151015LeuProLeuLeuIleMetCysIleThrTyrTyrAspIleMetLeuMet202530 ThrAlaSerIlePheAsnLeuMetAlaIleSerValGly354045(2) INFORMATION FOR SEQ ID NO:308:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 47 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single (D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:308:AspTyrAlaIleValTyrGlyLeuValAspGlyLeuValThrPheTyr151015LeuProL euLeuIleMetCysIleSerSerAspIleMetLeuHisThr202530ThrAlaSerThrIlePheAsnLeuMetAlaThrIleThrValGly 354045(2) INFORMATION FOR SEQ ID NO:309:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 47 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:309:CysAspValVal TyrAspGlyLeuValThrPheTyrLeuProLeuLeu151015IleMetCysIleThrTyrTyrAspIleMetLeuPheTyrValCysThr 202530AlaSerIlePheSerSerAsnLeuCysAlaIleSerSerValGly354045(2) INFORMATION FOR SEQ ID NO:310:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 43 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:310:CysAspValPheValPheValAspIleMetLeuLeuValIlePheLeu1 51015GlyLeuValIleValIleProPheValLeuIleIleValSerTyrAla202530SerIlePhe AsnLeuCysAlaIleSerValGly3540(2) INFORMATION FOR SEQ ID NO:311:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 42 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:311:TyrAlaIlePheValLeuTyrAspIleMetLeuLeuValIlePheLeu151015GlyLeuValIleValIleProPheValLeuIleIleV alSerTyrAla202530IlePheAsnLeuCysAlaIleSerValGly3540(2) INFORMATION FOR SEQ ID NO:312:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 44 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:312:AspTyrAlaIlePheValPheValAspIleMetLeuMetLeuValIle15 1015PheLeuGlyLeuValIleValIleProPheValLeuIleIleValSer202530TyrAlaIlePheAsnLeu MetAlaIleSerValGly3540(2) INFORMATION FOR SEQ ID NO:313:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 46 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:313: AspTyrAlaIlePheValPheValAspIleMetLeuHisThrLeuVal151015IlePheLeuGlyLeuValIleValIleProPheValLeuIleI leVal202530SerTyrAlaIlePheAsnLeuMetAlaThrIleThrValGly354045(2) INFORMATION FOR SEQ ID NO:314:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 48 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:314:CysAspValAlaValValTyrSerSerAspIleMetLeuPheLeuVal 151015IlePheLeuGlyLeuValIleValIleProPheValLeuIleIleVal202530 SerTyrAlaIlePheSerSerAsnLeuCysAlaIleSerSerValGly354045(2) INFORMATION FOR SEQ ID NO:315:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 48 amino acids(B) TYPE: amino acid (C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:315:CysAspValPheValPheValAspIleMetLeuCysThrAlaLeuMet151015IleTyrIleLeuGlyGlyLeuIleIleIleIleProPheLeuLeuIle202530ValMetSerTyrValSerIlePheAsnLeuCysAlaIleSerVal Gly354045(2) INFORMATION FOR SEQ ID NO:316:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 48 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:316: TyrAlaIlePheValLeuTyrAspIleMetLeuCysThrAlaLeuMet151015IleTyrIleLeuGlyGlyLeuIleIleIleIleProPheLeuL euIle202530ValMetSerTyrValSerIlePheAsnLeuCysAlaIleSerValGly354045(2) INFORMATION FOR SEQ ID NO:317:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 49 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:317:AspTyrAlaIlePheValPheValAspIleMetLeuMetThrAla Ser151015IlePheAsnLeuMetIleTyrIleLeuGlyGlyLeuIleIleIleIle2025 30ProPheLeuLeuIleValMetSerTyrValLeuMetAlaIleSerVal354045Gly(2) INFORMATION FOR SEQ ID NO:318:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 46 amino acids (B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:318:AspTyrAlaIlePheValPheValAspIleMetLeuHisThrThrAla1510 15SerThrIleLeuMetIleTyrIleLeuGlyGlyLeuIleIleIleIle202530ProPheLeuLeuIleValMetSerTyrVal IleThrValGly354045(2) INFORMATION FOR SEQ ID NO:319:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 49 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide( xi) SEQUENCE DESCRIPTION: SEQ ID NO:319:CysAspValAlaValValTyrSerSerAspIleMetLeuPheTyrVal151015CysThrAlaTyrIleLeuGlyGlyLeuIleProP heLeuLeuIleVal202530MetThrTyrValSerIlePheThrAsnLeuCysAlaIleSerSerVal3540 45Gly(2) INFORMATION FOR SEQ ID NO:320:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 48 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:320:CysAspValPheValPheValAspIle MetLeuCysThrAlaSerIle151015PheAsnLeuLeuMetIleHisIleMetGluValIleIleIleValIle20 2530ProPheValLeuIleValIleSerTyrAlaCysAlaIleSerValGly354045(2) INFORMATION FOR SEQ ID NO:321:(i) SEQUENCE CHARACTERISTICS:(A ) LENGTH: 48 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:321:TyrAlaIlePheValLeuTyrAspIleMetLeuCysThrAlaSerIle15 1015PheAsnLeuLeuMetIleHisIleMetGluValIleIleIleValIle202530ProPheValLeuIleValIle SerTyrAlaCysAlaIleSerValGly354045(2) INFORMATION FOR SEQ ID NO:322:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 45 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:322:AspTyrAlaIlePheValPheValAspIleMetLeuMetThrAlaSer151015IlePheLeuMetIleHisI leMetGluValIleIleIleValIlePro202530PheValLeuIleValIleSerTyrAlaIleSerValGly3540 45(2) INFORMATION FOR SEQ ID NO:323:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 46 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:323:AspTyrAlaIlePheValPheValAspIle MetLeuHisThrThrAla151015SerThrIleLeuMetIleHisIleMetGluValIleIleIleValIle20 2530ProPheValLeuIleValIleSerTyrAlaIleThrValGly354045(2) INFORMATION FOR SEQ ID NO:324:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 51 amino acids (B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:324:CysAspValAlaValValTyrSerSerAspIleMetLeuPheTyrVal1510 15CysThrAlaSerIlePheLeuMetIleHisIleMetGluValIleIle202530IleValIleProPheValLeuIleValIle SerTyrAlaAlaIleSer354045SerValGly50(2) INFORMATION FOR SEQ ID NO:325:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 97 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:325:AsnTrpProAlaLeuSerIleValValIleIleIleAsnThrIleGly151015Gly AsnIleLeuValIleMetAlaValSerIleTyrThrSerLeuAsp202530ValMetLeuCysThrAlaSerIleLeuAsnLeuLeuIleSerLeuPhe 354045ValLeuIleGlySerPheValAlaPhePheIleProLeuThrIleMet505560ValIleThrT yrPheLeuPheAsnValPhePheValTrpIleGlyTyr65707580ValCysSerSerSerLeuGlyIleAsnProValIleIleTyrThrLeu 859095Phe(2) INFORMATION FOR SEQ ID NO:326:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 97 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:326:AsnTrpProAlaLeuSerIleValValIleIleIleAsnThrIleGly151015GlyAsnIleLeuValIleMetAlaValThrIleTyrT hrThrLeuAsp202530ValMetLeuCysThrAlaThrIleLeuAsnLeuLeuIleSerLeuPhe3540 45ValLeuIleGlyThrPheValAlaPhePheIleProLeuThrIleMet505560ValIleThrTyrPheLeuPheAsnValPhePheValTrpIleGly Tyr65707580ValCysThrThrThrLeuGlyIleAsnProValIleIleTyrThrLeu8590 95Phe(2) INFORMATION FOR SEQ ID NO:327:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 97 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:327:AsnTrpProAlaLeuThrIleValV alIleIleIleAsnThrIleGly151015GlyAsnIleLeuValIleMetAlaValSerIleTyrThrThrLeuAsp20 2530ValMetLeuCysThrAlaThrIleLeuAsnLeuLeuIleThrLeuPhe354045ValLeuIleGlyThrPheValAla PhePheIleProLeuThrIleMet505560ValIleThrTyrPheLeuPheAsnValPhePheValTrpIleGlyTyr6570 7580ValCysSerThrSerLeuGlyIleAsnProValIleIleTyrThrLeu859095Phe(2) INFORMATION FOR SEQ ID NO:328: (i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 95 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:328:AsnTrpProAlaLeuThrIleValValIleIleIleAsnThrIleGly1 51015GlyAsnIleLeuValIleMetAlaValThrIleTyrThrThrLeuAsp202530ValMet LeuCysThrAlaThrIleLeuAsnLeuLeuIleThrLeuPhe354045ValLeuIleGlyThrPheValAlaPhePheIleProLeuThrIleMet50 5560ValIleThrTyrPheLeuPheAsnValPhePheValTrpIleGlyTyr65707580ValCysT hrLeuGlyIleAsnProValIleIleTyrThrLeuPhe859095(2) INFORMATION FOR SEQ ID NO:329:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 97 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:329:AsnTrpLysAsnTrpSerAlaLeuLeuThrThrValValIleIleLeu151015Thr IleAlaGlyAsnIleLeuValIleMetAlaValSerSerLeuAsp202530ValMetLeuCysThrAlaSerIleLeuAsnLeuLeuIleSerLeuPhe 354045ValLeuIleGlySerPheValAlaPhePheIleProLeuThrIleMet505560ValIleThrT yrPheLeuPheAsnValPhePheValTrpIleGlyTyr65707580ValCysSerSerSerLeuGlyIleAsnProValIleIleTyrThrLeu 859095Phe(2) INFORMATION FOR SEQ ID NO:330:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 98 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:330:IleThrIleThrValValLeuAlaValLeuIleLeuIleThrValAla151015GlyAsnValValValCysIleAlaValGlySerIleT yrThrSerLeu202530AspValMetLeuCysThrAlaSerIleLeuAsnLeuLeuIleSerLeu3540 45PheValLeuIleGlySerPheValAlaPhePheIleProLeuThrIle505560MetValIleThrTyrPheLeuPheAsnValPhePheValTrpIle Gly65707580TyrValCysSerSerSerLeuGlyIleAsnProValIleIleTyrThr8590 95LeuPhe(2) INFORMATION FOR SEQ ID NO:331:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 93 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:331:ThrLeuThrLeuValCysIleA laCysLeuSerLeuThrValPheGly151015AsnValLeuValIleIleAlaValPheSerLeuAspValMetLeuCys20 2530ThrAlaSerIleLeuAsnLeuLeuIleSerLeuPheValLeuIleGly354045SerPheValAlaPhePheIle ProLeuThrIleMetValIleThrTyr505560PheLeuPheAsnValPhePheValTrpIleGlyTyrValCysSerSer6570 7580SerLeuGlyIleAsnProValIleIleTyrThrLeuPhe8590(2) INFORMATION FOR SEQ ID NO:332:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 99 amino acids(B ) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:332:ThrAlaAlaIleAlaAlaAlaIleThrPheLeuIleLeuPheThrIle1510 15PheGlyAsnAlaLeuValIleIleAlaValLeuSerIleTyrThrSer202530LeuAspValMetLeuCysThrAlaSerIleLeuAsn LeuLeuIleSer354045LeuPheValLeuIleGlySerPheValAlaPhePheIleProLeuThr505560IleMetValIleThrTyrPheLeuPheAsnValPhePheValTrpIle65707580GlyTyrValCysSerSerSerLeuGlyIleAsnProV alIleIleTyr859095ThrLeuPhe(2) INFORMATION FOR SEQ ID NO:333:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 124 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:333:AlaIleSerValGlyLeuValLeuGlyAlaPheIleLeuPheAlaIle151015ValGlyAsnIleLeu ValIleLeuSerValAlaAsnTrpProAlaLeu202530SerIleValValIleIleIleAsnThrIleGlyGlyAsnIleLeuVal35 4045IleMetAlaValSerIleTyrThrSerLeuAspValMetLeuCysThr505560AlaSerIleLeuAsnLeuLeuI leSerLeuPheValLeuIleGlySer65707580PheValAlaPhePheIleProLeuThrIleMetValIleThrTyrPhe 859095LeuPheAsnValPhePheValTrpIleGlyTyrValCysSerSerSer100105110LeuGlyIleAs nProValIleIleTyrThrLeuPhe115120(2) INFORMATION FOR SEQ ID NO:334:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 95 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi ) SEQUENCE DESCRIPTION: SEQ ID NO:334:AlaAlaLeuAlaGlyAlaLeuLeuAlaLeuAlaValLeuAlaThrVal151015GlyGlyAsnLeuLeuValIleValAlaIleAlaSer LeuAspValMet202530LeuCysThrAlaSerIleLeuAsnLeuLeuIleSerLeuPheValLeu3540 45IleGlySerPheValAlaPhePheIleProLeuThrIleMetValIle505560ThrTyrPheLeuPheAsnValPhePheValTrpIleGlyTyrV alCys65707580SerSerSerLeuGlyIleAsnProValIleIleTyrThrLeuPhe8590 95(2) INFORMATION FOR SEQ ID NO:335:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 93 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:335:ThrAlaGlyAspCysLeuIleMetLeuIleValLeu LeuIleValAla151015GlyAsnValLeuValIleValAlaIleSerLeuAspValMetLeuCys2025 30ThrAlaSerIleLeuAsnLeuLeuIleSerLeuPheValLeuIleGly354045SerPheValAlaPhePheIleProLeuThrIleM etValIleThrTyr505560PheLeuPheAsnValPhePheValTrpIleGlyTyrValCysSerSer657075 80SerLeuGlyIleAsnProValIleIleTyrThrLeuPhe8590(2) INFORMATION FOR SEQ ID NO:336:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 98 amino acids(B) TYPE: amino acid( C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:336:ValIleThrIleAlaValValThrAlaValValSerLeuMetThrIle151015 ValGlyAsnValLeuValMetIleSerPheSerIleTyrThrSerLeu202530AspValMetLeuCysThrAlaSerIleLeuAsnLeuLeuIleSerLeu 354045PheValLeuIleGlySerPheValAlaPhePheIleProLeuThrIle505560MetValI leThrTyrPheLeuPheAsnValPhePheValTrpIleGly65707580TyrValCysSerSerSerLeuGlyIleAsnProValIleIleTyrThr 859095LeuPhe(2) INFORMATION FOR SEQ ID NO:337:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 98 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:337:MetValPheIleAlaThrValArgGlySerLeuSerLeuValThrVal151015ValGlyAsnIleLeuValMetLeuSerIleS erIleTyrThrSerLeu202530AspValMetLeuCysThrAlaSerIleLeuAsnLeuLeuIleSerLeu3540 45PheValLeuIleGlySerPheValAlaPhePheIleProLeuThrIle505560MetValIleThrTyrPheLeuPheAsnValPhePheVal TrpIleGly65707580TyrValCysSerSerSerLeuGlyIleAsnProValIleIleTyrThr8590 95LeuPhe(2) INFORMATION FOR SEQ ID NO:338:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 97 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:338:TrpPheIleAlaPheL euThrGlyIleLeuAlaLeuValThrIleIle151015GlyAsnIleLeuValIleValSerPheSerIleTyrThrSerLeuAsp 202530ValMetLeuCysThrAlaSerIleLeuAsnLeuLeuIleSerLeuPhe354045ValLeuIleGlySer PheValAlaPhePheIleProLeuThrIleMet505560ValIleThrTyrPheLeuPheAsnValPhePheValTrpIleGlyTyr6570 7580ValCysSerSerSerLeuGlyIleAsnProValIleIleTyrThrLeu859095Phe(2) INFORMATION FOR SEQ ID NO:339:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 102 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:339:AsnTrpProAlaLeuSerIleValValIleIleIleAsnThrIleGly 151015GlyAsnIleLeuValIleMetAlaPhePheAlaCysPheValLeuVal202530 LeuThrGlnSerSerIlePheSerLeuLeuAlaIleAlaIleAsnLeu354045LeuIleSerLeuPheValLeuIleGlySerPheValAlaPhePheIle 505560ProLeuThrIleMetValIleThrTyrPheLeuPheAsnValPhePhe65707580 ValTrpIleGlyTyrValCysSerSerSerLeuGlyIleAsnProVal859095IleIleTyrThrLeuPhe100(2) INFORMATION FOR SEQ ID NO:340:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 96 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:340:AsnTrpProAlaLeuSerIleValValIleIleIleAsnThrIleGly 151015GlyAsnIleLeuValIleMetAlaPhePheAlaCysPheValLeuVal202530 LeuThrGlnSerSerIlePheSerLeuLeuAlaIleAlaIlePheVal354045LeuIleGlySerPheValAlaPhePheIleProLeuThrIleMetVal 505560IleThrTyrPheLeuPheAsnValPhePheValTrpIleGlyTyrVal65707580 CysSerSerSerLeuGlyIleAsnProValIleIleTyrThrLeuPhe859095(2) INFORMATION FOR SEQ ID NO:341:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 92 amino acids(B) TYPE: amino acid (C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:341:AsnTrpProAlaLeuSerIleValValIleIleIleAsnThrIleGly15101 5GlyAsnIleLeuValIleMetAlaValMetValAlaCysProValLeu202530IleLeuThrGlnSerSerIleIleAlaLeuLeuAlaIleAla ValSer354045PheValAlaPhePheIleProLeuThrIleMetValIleThrTyrPhe505560 LeuPheAsnValPhePheValTrpIleGlyTyrValCysSerSerSer65707580LeuGlyIleAsnProValIleIleTyrThrLeuPhe 8590(2) INFORMATION FOR SEQ ID NO:342:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 88 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:342:AsnTrpProAlaLeuSe rIleValValIleIleIleAsnThrIleGly151015GlyAsnIleLeuValIleMetAlaValLeuTrpLeuAlaLeuAspTyr2 02530ValAlaSerAsnAlaSerValLeuAsnLeuLeuLeuIleSerPhePhe354045PheIleProLeuThr IleMetValIleThrTyrPheLeuPheAsnVal505560PhePheValTrpIleGlyTyrValCysSerSerSerLeuGlyIleAsn6570 7580ProValIleIleTyrThrLeuPhe85(2) INFORMATION FOR SEQ ID NO:343:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 86 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single (D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:343:AsnTrpProAlaLeuSerIleValValIleIleIleAsnThrIleGly151015GlyAsnIleLe uValIleMetAlaValLeuTyrValValSerAsnAla202530SerValMetAsnLeuLeuIleIleSerSerPheValAlaPhePheIle3 54045ProLeuThrIleMetValIleThrTyrPheLeuPheAsnValPhePhe505560ValTrpIleGlyTyrVal CysSerSerSerLeuGlyIleAsnProVal65707580IleIleTyrThrLeuPhe85(2) INFORMATION FOR SEQ ID NO:344:(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 93 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:344:AsnTrpProAlaLeuSerIleValValIleIleIleAsnThrIleGly15 1015GlyAsnIleLeuValIleMetAlaValLeuTrpIleAlaIleAspTyr202530ValAlaSerAsnAl aSerValLeuAsnLeuLeuValIleSerPheGly354045SerPheValAlaPhePheIleProLeuThrIleMetValIleThrTyr50 5560PheLeuPheAsnValPhePheValTrpIleGlyTyrValCysSerSer65707580SerLeuGlyIleAsn ProValIleIleTyrThrLeuPhe8590(2) INFORMATION FOR SEQ ID NO:345:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 92 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:345:AsnTrpProAlaLeuSerIleValValIleIleIleAsnThrIleGly151015GlyAsnIleLeuValIleMetAlaValLeuPh eProPheLeuGlnLys202530SerSerValGlyIleThrValLeuAsnLeuCysAlaLeuSerGlySer3540 45PheValAlaPhePheIleProLeuThrIleMetValIleThrTyrPhe505560LeuPheAsnValPhePheValTrpIleGlyTyrValCys SerSerSer65707580LeuGlyIleAsnProValIleIleTyrThrLeuPhe8590(2) INFORMATION FOR SEQ ID NO:346: (i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 94 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:346:AsnTrpProAlaLeuSerIleValValIleIleIleAsnThrIleGly1 51015GlyAsnIleLeuValIleMetAlaValCysIleThrTyrLeuGlnTyr202530Le uGlyIleAsnAlaSerSerCysSerIleThrAlaPheThrIleIle354045GlySerPheValAlaPhePheIleProLeuThrIleMetValIleThr 505560TyrPheLeuPheAsnValPhePheValTrpIleGlyTyrValCysSer65707580Ser SerLeuGlyIleAsnProValIleIleTyrThrLeuPhe8590(2) INFORMATION FOR SEQ ID NO:347:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 92 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:347:AsnTrpProAlaLeuSerIleValValIleIleIleAsnThrIleGly151015GlyAsnIleLeuValIl eMetAlaValPheHisAsnPhePheProIle202530AlaAlaLeuPheAlaSerIleTyrSerMetThrAlaValAlaGlySer35 4045PheValAlaPhePheIleProLeuThrIleMetValIleThrTyrPhe505560LeuPheAsnValPhePheValTrp IleGlyTyrValCysSerSerSer65707580LeuGlyIleAsnProValIleIleTyrThrLeuPhe85 90(2) INFORMATION FOR SEQ ID NO:348:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 93 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO:348:AsnTrpProAlaLeuSerIleValValIleIleIleAsnTh rIleGly151015GlyAsnIleLeuValIleMetAlaValIleAlaSerAlaSerValSer2025 30PheAsnLeuTyrAlaSerValPheLeuLeuThrCysLeuSerIleGly354045SerPheValAlaPhePheIleProLeuThrIleMetVal IleThrTyr505560PheLeuPheAsnValPhePheValTrpIleGlyTyrValCysSerSer657075 80SerLeuGlyIleAsnProValIleIleTyrThrLeuPhe8590
Claims
  • 1. A polypeptide having the amino acid sequence of SEQ ID NO:2.
Parent Case Info

The present application is a continuation-in-part of U.S. Ser. No. 07/943,236, filed Sep. 10, 1992, now abandoned, which application is entirely incorporated herein by reference.

Non-Patent Literature Citations (4)
Entry
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Pharmac. Ther. 50:425-442, 1991, Jackson Structure and Function of G Protein Coupled Receptors.
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Nature 336:783-787, 22 Dec. 1988, Bunzow et al, Cloning and Expression of a rat D.sub.2 dopamine receptor cDNA.
Continuation in Parts (1)
Number Date Country
Parent 943236 Sep 1992