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.

1 . A method of stimulating, augmenting, increasing, and/or up-regulating T cell activity with a bioactive agent capable of blocking the interaction of zB7R1 with CD155. 
     
     
         2 . A method of inhibiting or down-regulating T cell activity with a bioactive agent capable of binding to zB7R1 and mimicking and/or augmenting the natural interaction of zB7R1 with CD155. 
     
     
         3 . The method of  claim 1  or  2 , where the bioactive agents may be selected from the group comprising of soluble zB7R1 polypeptides the sequence of which comprises a sequence having at least 95% identity with SEQ ID NO: 3 and fusion proteins, anti-zB7R1 antibodies, small molecule inhibitors of zB7R1, antisense oligonucleotides, or inhibitory RNA sequences. 
     
     
         4 . The method of  claim 1  or  2 , wherein the T cell is in a patient. 
     
     
         5 . The method of  claim 4 , wherein the patient is suffering from an immune related disorder. 
     
     
         6 . A method of treating an immune related disorder in a mammal by administering to said mammal a therapeutically effective amount of (a) a polypeptide of  claim 5 , (b) an agonist of said polypeptide, (c) an antagonist of said polypeptide, or (d) an antibody that binds to said polypeptide. 
     
     
         7 . 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.