Lymphocyte surface receptor that binds caml and methods of use thereof

Abstract

A novel lymphocyte receptor protein, its DNA sequence, and its role in the calcium activation pathway is described. The protein, or genetically engineered constructs encoding it, is shown to increase lymphocyte response, and to identify ligands of the protein receptor. Antibodies to the proteins of the invention are generated for diagnostic therapeutics. The protein and DNA can also be used for diagnostic purposes and for identifying agents for modulating the calcium induced activation pathway. A particular advantage of the present invention is that it provides lymphocyte activation of receptor found on all B cells, but only on a subset of T cells. The receptor can thus be targeted to specifically regulate B cell responses without affecting mature T cell activity. Such targeting specificity is always advantageous, particularly where an increase or decrease of antibody production is desired, e.g., during an infection (increase) or to avoid immune complex deposition complications (rheumatoid arthritis, glomerulonephritis, and other auto immune conditions).

1 . A transgenic mouse comprising a transgene encoding a fusion protein comprising an extracellular fragment of the TACI protein joined to the Fc domain of an immunoglobulin.  
     
     
         2 . The transgenic mouse of  claim 1 , wherein said transgenic mouse exhibits a suppressed immune system in comparison to a wild-type mouse.  
     
     
         3 . The transgenic mouse of  claim 1 , wherein said transgenic mouse exhibits a decreased B-cell response in comparison to a wild-type mouse.  
     
     
         4 . The transgenic mouse of  claim 1 , wherein said extracellular fragment of the TACI protein is an N-terminal fragment of the TACI amino acid sequence shown in SEQ ID NO:2.  
     
     
         5 . The transgenic mouse of  claim 4 , wherein the extracellular fragment of the TACI protein is an N-terminal fragment the TACI amino acid sequence shown in SEQ ID NO:6.  
     
     
         6 . The transgenic mouse of  claim 5 , wherein the extracellular fragment comprises the TNFR_NGFR pattern shown in SEQ ID NO:11.  
     
     
         7 . The transgenic mouse of  claim 4 , wherein the extracellular fragment of the TACI protein comprises amino acids 1-151 of SEQ ID NO:2.