Novel Polypeptides Involved in Immune Response

Abstract

Polypeptides which comprise a receptor-ligand pair involved in T-cell activation are disclosed. Nucleic acid molecules encoding the polypeptides, and vectors and host cells for expressing the polypeptides are also disclosed. The polypeptides, or agonists and antagonists thereof, are used to treat T-cell mediated disorders.

1 - 9 . (canceled) 
     
     
         10 . A polypeptide encoded by an isolated nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of:
 a) the nucleotide sequence as set forth in  FIG. 2A  (SEQ ID NO: 11) or  FIG. 3A  (SEQ ID NO: 6) or  FIG. 12A  (SEQ ID NO: 16);   b) the nucleotide sequence encoding the polypeptide as set forth in  FIG. 2A  (SEQ ID NO: 6) from residues 1-322 or from residues 47-322, or as set forth in  FIG. 3A  (SEQ ID NO: 11) from residues 1-288 or from residues 19-288, 20-288, 21-288, 22-288, 24-288, or 28-288 or as set forth in  FIG. 12A  from residues 1-302, or from residues 19-302, 20-302, 21-302, 22-302, 24-302 or 28-302;   c) a nucleotide sequence encoding a polypeptide that is at least about 70 percent identical to the polypeptide as set forth in  FIG. 2A  (SEQ ID NO: 6) or  FIG. 3A  (SEQ ID NO: 11) or  FIG. 12A  (SEQ ID NO: 6);   d) a naturally occurring allelic variant or alternate splice variant of any of (a), (b) or (c);   e) a nucleotide sequence of (b), (c) or (d) encoding a polypeptide fragment of at least about 25, 50, 75, 100, or greater than 100 amino acid residues;   f) a nucleotide sequence of (a), (b) or (c) comprising a fragment of at least about 10, 15, 20, 25, 50, 75, 100, or greater than 100 nucleotides; and   g) a nucleotide sequence which hybridizes under stringent conditions to the complement of the sequence of any of (a)-(f).   
     
     
         11 . (canceled) 
     
     
         12 . An isolated polypeptide comprising the amino acid sequence selected from the group consisting of:
 a) the amino acid sequence as set forth in  FIG. 2A  (SEQ ID NO: 7) or  FIG. 3A  (SEQ ID NO: 12) or  FIG. 12A  (SEQ ID NO: 17);   b) the mature amino acid sequence as set forth in  FIG. 2A  (SEQ ID NO: 7) comprising a mature amino terminus at residues 47, or  FIG. 3A  (SEQ ID NO: 12) comprising a mature amino terminus at any of residues 19, 20, 21, 22, 24 or 28, or  FIG. 12A  (SEQ ID NO: 17) comprising a mature amino terminus at any of residues 19, 20, 21, 22, 24, or 28;   c) a fragment of the amino acid sequence set forth in  FIG. 2A  (SEQ ID NO: 7) or  FIG. 3A  (SEQ ID NO: 12) or  FIG. 12A  (SEQ ID NO: 17) comprising at least about 25, 50, 75, 100, or greater than 100 amino acid residues;   d) an ortholog of (a), (b) or (c); and   e) an allelic variant or alternative splice variant of (a), (b), (c) or (d).   
     
     
         13 - 18 . (canceled) 
     
     
         19 . A composition comprising the polypeptide of any one of  claim 10  or  12  and a pharmaceutically acceptable carrier, adjuvant, solubilizer, stabilizer or anti-oxidant. 
     
     
         20 . A polypeptide comprising a derivative of the polypeptide of any one of  claim 10  or  12 . 
     
     
         21 . The polypeptide of  claim 20  which is covalently modified with a water-soluble polymer. 
     
     
         22 . A fusion polypeptide comprising the polypeptide of any one of  claim 10  or  12  fused to a heterologous amino acid sequence. 
     
     
         23 . The fusion polypeptide of  claim 22  wherein the heterologous amino acid sequence is an IgG constant domain or fragment thereof. 
     
     
         24 . (canceled) 
     
     
         25 . A method of diagnosing a T-cell mediated disorder or a susceptibility to a T-cell mediated disorder in an animal comprising:
 a) determining the presence or amount of expression of the polypeptide of any one of  claim 10  or  12 ; and   b) diagnosing a T-cell mediated disorder or a susceptibility to a T-cell mediated disorder based on the presence or amount of expression of the polypeptide.   
     
     
         26 . A method of identifying a test molecule which binds to a polypeptide comprising;
 a) contacting the polypeptide of any one of  claim 10  or  12  with a test molecule; and   b) determining the extent of binding of the polypeptide to the test molecule.   
     
     
         27 . The method of  claim 26  further comprising determining the activity of the polypeptide when bound to the compound. 
     
     
         28 . A method of regulating T-cell activation or proliferation in an animal comprising administering to the animal an isolated nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of:
 a) the nucleotide sequence as set forth in  FIG. 2A  (SEQ ID NO: 11) or  FIG. 3A  (SEQ ID NO: 6) or  FIG. 12A  (SEQ ID NO: 16);   b) the nucleotide sequence encoding the polypeptide as set forth in  FIG. 2A  (SEQ ID NO: 6) from residues 1-322 or from residues 47-322, or as set forth in  FIG. 3A  (SEQ ID NO: 11) from residues 1-288 or from residues 19-288, 20-288, 21-288, 22-288, 24-288, or 28-288 or as set forth in  FIG. 12A  from residues 1-302, or from residues 19-302, 20-302, 21-302, 22-302, 24-302 or 28-302;   c) a nucleotide sequence encoding a polypeptide that is at least about 70 percent identical to the polypeptide as set forth in  FIG. 2A  (SEQ ID NO: 6) or  FIG. 3A  (SEQ ID NO: 11) or  FIG. 12A  (SEQ ID NO: 6);   d) a naturally occurring allelic variant or alternate splice variant of any of (a), (b) or (c);   e) a nucleotide sequence complementary to any of (a), (b) or (c);   f) a nucleotide sequence of (b), (c) or (d) encoding a polypeptide fragment of at least about 25, 50, 75, 100, or greater than 100 amino acid residues;   g) a nucleotide sequence of (a), (b) or (c) comprising a fragment of at least about 10, 15, 20, 25, 50, 75, 100, or greater than 100 nucleotides; and   h) a nucleotide sequence which hybridizes under stringent conditions to any of (a)-(g).   
     
     
         29 . A transgenic non-human mammal comprising the nucleic acid molecule of  claim 28 . 
     
     
         30 . A method of suppressing an immune response in an animal comprising administering to the animal an antagonist of CRP1 or B7RP1. 
     
     
         31 . The method of  claim 30  wherein the antagonist is an antibody which binds B7RP1. 
     
     
         32 - 38 . (canceled) 
     
     
         39 . A method of enhancing an immune response comprising administering B7RP1, a B7RP1 agonist or a CRP1 agonist. 
     
     
         40 . The method of  claim 39  further comprising administering a CD28 agonist. 
     
     
         41 . The method of  claim 39  further comprising administering B7.1 or B7.2 or both. 
     
     
         42 . A method of treating cancer or viral infection comprising
 administering B7RP1 or an agonist of CRP1, optionally in combination with B7.1 or B7.2.