Family of immunoregulators designated leukocyte immunoglobulin-like receptors (LIR)

Abstract

A new family of immunoreceptor molecules of the immunoglobulin superfamily, (LIR) polypeptides is described. Disclosed are sequences encoding LIR family members and their deduced amino acid sequences, polypeptides encoded by DNA that hybridizes to defined nucleotide sequences, processes for producing polypeptides of the LIR family, and specific antibodies directed against LIR polypeptides. LIR family members can be used to treat autoimmune diseases and disease states associated with suppressed immune function.

What is claimed is:  
     
         1 . An isolated nucleic acid molecule encoding an LIR polypeptide, wherein said LIR polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:22, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36 and SEQ ID NO:38.  
     
     
         2 . An isolated nucleic acid molecule of  claim 1 , wherein the nucleic acid molecule has a nucleotide sequence selected from the group consisting of SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:21, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35 and SEQ ID NO:37.  
     
     
         3 . An isolated nucleic acid molecule according to  claim 1 , wherein the nucleic acid molecule comprises nucleotides 171-1040 of SEQ ID NO:11.  
     
     
         4 . An isolated nucleic acid molecule according to  claim 1 , wherein the nucleic acid molecule comprises nucleotides 183-1652 of SEQ ID NO:13.  
     
     
         5 . An isolated nucleic acid molecule according to  claim 1 , wherein the nucleic acid molecule comprises nucleotides 67-1839 of SEQ ID NO:21.  
     
     
         6 . An isolated nucleic acid molecule according to  claim 1 , wherein the nucleic acid molecule comprises nucleotides 69-968 of SEQ ID NO:29.  
     
     
         7 . An isolated nucleic acid molecule according to  claim 1 , wherein the nucleic acid molecule comprises nucleotides 95-958 of SEQ ID NO:31.  
     
     
         8 . An isolated nucleic acid molecule according to  claim 1 , wherein the nucleic acid molecule comprises nucleotides 115-912 of SEQ ID NO:33.  
     
     
         9 . An isolated nucleic acid molecule according to  claim 1 , wherein the nucleic acid molecule comprises nucleotides 73-834 of SEQ ID NO:35.  
     
     
         10 . An isolated nucleic acid molecule according to  claim 1 , wherein the nucleic acid molecule comprises nucleotides 1-1350 of SEQ ID NO:37.  
     
     
         11 . An isolated nucleic acid molecule encoding a soluble LIR polypeptide, wherein said LIR polypeptide comprises an amino acid sequence selected from the group consisting of: 
 the extracellular domain of a LIR family member, wherein the extracellular domain is selected from the group consisting of:    amino acids x 5  to 261 of SEQ ID NO:12, wherein x 5  is amino acid 1 or 17;    amino acids x 6  to 461 of SEQ ID NO:14, wherein x 6  is amino acid 1 or 17;    amino acids x 6  to 456 of SEQ ID NO:22 10 , wherein x is amino acid 1 or 17;    amino acids x 11  to 262 of SEQ ID NO:30, wherein x 11  is amino acid 1 or 35;    amino acids x 12  to 250 of SEQ ID NO:32, wherein x 12  is amino acid 1 or 36;    amino acids x 13  to 265 of SEQ ID NO:34, wherein x 13  is amino acid 1 or 35;.    amino acids x 14  to 253 of SEQ ID NO:36, wherein x 14  is amino acid 1 or 36; and    amino acids 1-393 of SEQ ID NO:38.    
     
     
         12 . An isolated nucleic acid molecule encoding a soluble LIR polypeptide comprising at least one Ig-like domain, wherein said LIR polypeptide comprises at least 85 amino acids selected from the group consisting of: 
 amino acids x 5  to 261 of SEQ ID NO:12, wherein x 5  is amino acid 1 or 17;    amino acids x 6  to 461 of SEQ ID NO:14, wherein X 6  is amino acid 1 or 17;    amino acids x 10  to 456 of SEQ ID NO:22 10 , wherein x is amino acid 1 or 17;    amino acids x 11  to 262 of SEQ ID NO:30, wherein x 11  is amino acid 1 or 35;    amino acids x 12  to 250 of SEQ ID NO:32, wherein x 12  is amino acid 1 or 36;    amino acids x 13  to 265 of SEQ ID NO:34, wherein x 13  is amino acid 1 or 35;    amino acids x 14  to 253 of SEQ ID NO:36, wherein x 14  is amino acid 1 or 36; and    amino acids 1 to 393 of SEQ ID NO:38.    
     
     
         13 . An isolated polypeptide encoded by a nucleic acid molecule of  claim 1 .  
     
     
         14 . An antibody capable of binding specifically to a polypeptide of  claim 13 .  
     
     
         15 . A nucleic acid molecule that encodes a fusion protein comprising the Fc region of Ig and an amino acid sequence selected from the group consisting of: 
 amino acids x 5  to 261 of SEQ ID NO:12, wherein x 5  is amino acid 1 or 17;    amino acids x 6  to 461 of SEQ ID NO:14, wherein x 6  is amino acid 1 or 17;    amino acids x 10  to 456 of SEQ ID NO:22 10 , wherein x is amino acid 1 or 17;    amino acids x 11  to 262 of SEQ ID NO:30, wherein x 11  is amino acid 1 or 35;    amino acids x 12  to 250 of SEQ ID NO:32, wherein x 12  is amino acid 1 or 36;    amino acids x 13  to 265 of SEQ ID NO:34, wherein x 3  is amino acid 1 or 35;    amino acids x 14  to 253 of SEQ ID NO:36, wherein x 14  is amino acid 1 or 36;    amino acids 1 to 393 of SEQ ID NO:38.    
     
     
         16 . A recombinant expression vector comprising a nucleic acid molecule according to  claim 1 .  
     
     
         17 . A process for preparing an LIR polypeptide, the process comprising culturing a host cell transformed with an expression vector of  claim 16  under conditions that promote expression of said polypeptide, and recovering said polypeptide.  
     
     
         18 . A composition comprising a pyhsiologically acceptable carrier and a polypeptide of  claim 13 .  
     
     
         19 . A host cell transformed or transfected with an expression vector according to  claim 16.