Compositions and methods for modulating lymphocte activity

Abstract

The present invention provides a novel lymphocyte inhibitory receptor termed BTLA which is expressed on both T and B cells, and identifies B7 family member B7x as interacting with BTLA to attenuate lymphocyte activity. Methods and compositions for modulating BTLA-mediated negative signaling and interfering with the interaction of BTLA and B7x for therapeutic, diagnostic and research purposes are also provided.

1 - 78 . (canceled) 
     
     
         79 . An isolated BTLA protein produced by the process comprising culturing a host cell under conditions suitable for the expression of BTLA protein, wherein the host cell comprises an expression vector comprising a recombinant BTLA nucleic acid encoding a BTLA protein having at least 98% identity to the amino acid sequence set forth in SEQ ID NO:8 operably linked to regulatory sequences recognizable by the host cell. 
     
     
         80 . An isolated BTLA protein, wherein the protein comprises an amino acid sequence encoded by a recombinant BTLA nucleic acid encoding a BTLA protein having at least 98% identity to the amino acid sequence set forth in SEQ ID NO:8, wherein said BTLA protein comprises an extracellular V-like Ig domain, a transmembrane region, and an intracellular domain, and is capable of inducible association with SHP-2 in T cells. 
     
     
         81 . An isolated BTLA protein, comprising an amino acid sequence having at least about 98% identity to the amino acid sequence set forth in SEQ ID NO:8 or 10. 
     
     
         82 . The isolated BTLA protein of  claim 81 , further comprising an extracellular V-like Ig domain, a transmembrane region, and an intracellular domain that comprises a Grb2 interaction site and two ITIM sequences. 
     
     
         83 . (canceled) 
     
     
         84 . The isolated BTLA protein of  claim 81 , wherein the protein is capable of interacting with SHP-1, SHP-2, or both SHP-1 and SHP-2. 
     
     
         85 . The isolated BTLA protein of  claim 81 , wherein the protein has BTLA signaling activity. 
     
     
         86 . The isolated BTLA protein of  claim 81 , wherein the protein is capable of inhibiting lymphocyte activity. 
     
     
         87 . The isolated BTLA protein of  claim 81 , further comprising the amino acid sequence set forth in SEQ ID NO:8 or 10.