Compositions and methods for modulating immune responses

Abstract

The present invention provides a newly identified B7 receptor, zB7R1 that functions as lymphocyte inhibitory receptor, which is a PD-1-like molecule and is expressed on T cells. The present invention also provides the discovery of zB7R1's ability to bind to CD155. Methods and compositions for modulating zB7R1-mediated negative signaling and interfering with the interaction of its counter-receptor for therapeutic, diagnostic and research purposes are also provided.

What is claimed is: 
     
         1 . A method of treating an immune related disorder in a mammal by administering to said mammal a therapeutically effective amount of a zB7R1 fusion protein. 
     
     
         2 . The method of  claim 1  wherein the zB7R1 fusion protein comprises the extracellular domain of B7R1 shown in SEQ ID NO: 3 and an immunoglobulin heavy chain constant region (Fc). 
     
     
         3 . The method of  claim 2  wherein the zB7R1 fusion protein is zB7R1-Fc coded by the nucleotide sequence shown in SEQ ID NO: 61. 
     
     
         4 . The method of  claim 1  wherein the zB7R1 fusion protein comprises the extracellular domain of B7R1 shown in SEQ ID NO: 3 and the vasodialator-activated phosphoprotein (VASP) tetramerization domain. 
     
     
         5 . The method of  claim 4  wherein the zB7R1 fusion protein is zB7R1-VASP coded by the nucleotide sequence shown in SEQ ID NO: 62. 
     
     
         6 . A method of identifying antibodies to zB7R1, the method comprising the steps of:
 a. constructing a Baf3-STAT-luciferase reporter cell line expressing a chimera of the extracellular domain of zB7R1 and the transmembrane and intracellular domains of mouse GCSFR;   b. incubating antibodies of interest with the Baf3-STAT-luciferase reporter cells;   c. isolating the reporter cells from the antibody;   d. lysing the reporter cells;   e. measuring for activation of the STAT reporter construct by adding luciferase substrate and   f. measuring the light generated following addition of substrate.