Chemokine receptor materials and methods

Abstract

The present invention provides polynucleotides that encode the chemokine receptors 88-2B or 88C and materials and methods for the recombinant production of these two chemokine receptors. Also provided are assays utilizing the polynucleotides which facilitate the identification of ligands and modulators of the chemokine receptors. Receptor fragments, ligands, modulators, and antibodies are useful in the detection and treatment of disease states associated with the chemokine receptors such as atherosclerosis, rheumatoid arthritis, tumor growth suppression, asthma, viral infection, AIDS, and other inflammatory conditions.

1 .- 50 . (Canceled)  
     
     
         51 . A method of modulating chemokine receptor 88C-mediated HIV or SIV infection of cells comprising the step of administering to a mammalian subject a composition comprising an antibody selected from the group consisting of: 
 (a) an antibody that specifically binds to the extracellular domain of a chemokine receptor 88C polypeptide comprising the amino acid sequence in SEQ ID NO: 2, wherein said antibody fails to cross-react with an MCP-1 receptor (CCCKR-2); and    (b) an antibody that specifically binds to a peptide consisting of amino acids 1 to 20 of SEQ ID NO: 2;    wherein the mammalian subject is infected with HIV or SIV, and wherein the antibody is administered in an amount effective to modulate HIV or SIV infection of 88C-expressing cells in said subject.    
     
     
         52 . The method according to  claim 51  wherein said antibody is a humanized antibody.  
     
     
         53 . A method of modulating chemokine receptor 88C-mediated HIV or SIV infection of cells comprising the step of administering to a mammalian subject a composition comprising a polypeptide comprising an antigen-binding fragment of an antibody selected from the group consisting of: 
 (a) an antibody that specifically binds to the extracellular domain of a chemokine receptor 88C polypeptide comprising the amino acid sequence in SEQ ID NO: 2, wherein said antibody fails to cross-react with an MCP-1 receptor (CCCKR-2); and    (b) an antibody that specifically binds to a peptide consisting of amino acids 1 to 20 of SEQ ID NO: 2;    wherein the mammalian subject is infected with HIV or SIV, and wherein the antibody is administered in an amount effective to modulate HIV or SIV infection of 88C-expressing cells in said subject.    
     
     
         54 . A method for inhibiting human or simian immunodeficiency virus (HIV or SIV) infection of cells, comprising the step of contacting cells at risk for infection with HIV or SIV with an antibody selected from the group consisting of: 
 (a) an antibody that specifically binds to the extracellular domain of a chemokine receptor 88C polypeptide comprising the amino acid sequence in SEQ ID NO: 2, wherein said antibody fails to cross-react with an MCP-1 receptor (CCCKR-2); and    (b) an antibody that specifically binds to a peptide consisting of amino acids 1 to 20 of SEQ ID NO: 2.    wherein the antibody is administered in an amount effective to inhibit HIV or SIV infection of 88C-expressing cells in said subject.    
     
     
         55 . The method according to  claim 54  wherein said antibody is a humanized antibody.  
     
     
         56 . A method for inhibiting human or simian immunodeficiency virus (HIV or SIV) infection of cells, comprising the step of contacting cells at risk for infection with HIV or SIV with a polypeptide comprising an antigen-binding fragment of an antibody selected from the group consisting of: 
 (a) an antibody that specifically binds to the extracellular domain of a chemokine receptor 88C polypeptide comprising the amino acid sequence in SEQ ID NO: 2, wherein said antibody fails to cross-react with an MCP-1 receptor (CCCKR-2); and    (b) an antibody that specifically binds to a peptide consisting of amino acids 1 to 20 of SEQ ID NO: 2;    wherein the antibody is administered in an amount effective to inhibit HIV or SIV infection of 88C-expressing cells in said subject.    
     
     
         57 . A method according to  claim 51 , wherein the composition further comprises a pharmaceutically acceptable carrier.