B7-related nucleic acids and polypeptides useful for immunomodulation

Abstract

The present invention provides nucleic acids encoding B7-related factors that modulate the activation of immune or inflammatory response cells, such as T-cells. Also provided are expression vectors and fusion constructs comprising nucleic acids encoding B7-related polypeptides, including BSL1, BSL2, and BSL3. The present invention further provides isolated B7-related polypeptides, isolated fusion proteins comprising B7-related polypeptides, and antibodies that are specifically reactive with B7-related polypeptides, or portions thereof. In addition, the present invention provides assays utilizing B7-related nucleic acids, polypeptides, or peptides. The present invention further provides compositions of B7-related nucleic acids, polypeptides, fusion proteins, or antibodies that are useful for the immunomodulation of a human or animal subject.

What is claimed is:  
     
         1 . An isolated nucleic acid fusion molecule consisting of a nucleotide sequence encoding an amino acid sequence selected from the group consisting of SEQ ID NO:133 and SEQ ID NO:135.  
     
     
         2 . A vector comprising the isolated nucleic acid fusion molecule according to  claim 1 .  
     
     
         3 . A host cell comprising the vector according to  claim 2 , wherein the host cell is selected from the group consisting of bacterial, yeast, insect, mammalian, and plant cells.  
     
     
         4 . An isolated fusion polypeptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NO:133 and SEQ ID NO:135.  
     
     
         5 . An antibody that binds to the isolated fusion polypeptide according to  claim 4 .  
     
     
         6 . The antibody according to  claim 5  which is monoclonal.  
     
     
         7 . A hybridoma cell which produces the monoclonal antibody according to  claim 6 .  
     
     
         8 . A method of decreasing T-cell proliferation in a subject comprising: 
 administering to the subject a pharmaceutical composition comprising an isolated fusion polypeptide consisting of amino acid sequence SEQ ID NO:9, and a physiologically acceptable carrier, diluent, or excipient, in an amount effective to decrease T-cell proliferation.    
     
     
         9 . The method according to  claim 8 , wherein the subject is affected with a condition selected from the group consisting of tissue rejection, bone marrow rejection, organ transplant rejection, graft versus host disease, psoriasis, chronic obstructive pulmonary disease, asthma, atherosclerosis, rheumatoid arthritis, multiple sclerosis, Lupus erythematosus, Hashimoto's thyroiditis, primary mixedema, Graves' disease, pernicious anemia, autoimmune atrophic gastritis, insulin dependent diabetes mellitus, good pasture's syndrome, myasthenia gravis, pemphigus, Crohn's disease, sympathetic opthalmia, autoimmune uveitis, autoimmune hemolytic anemis, idiopathic thrombocytopenia, primary biliary cirrhosis, ulcerative colitis, Sjogren's syndrome, polymyositis, and mixed connective tissue disease.  
     
     
         10 . The method according to  claim 8 , wherein the pharmaceutical composition is co-administered with a pharmaceutical composition comprising a monoclonal antibody that binds to a polypeptide consisting of the amino acid sequence SEQ ID NO:7, and a physiologically acceptable carrier, diluent, or excipient.  
     
     
         11 . A method of decreasing T-cell proliferation in a subject comprising: 
 administering to the subject a pharmaceutical composition comprising a monoclonal antibody that binds to a polypeptide consisting of the amino acid sequence SEQ ID NO:7, and a physiologically acceptable carrier, diluent, or excipient, in an amount effective to decrease T-cell proliferation.    
     
     
         12 . The method according to  claim 11 , wherein the subject is affected with a condition selected from the group consisting of tissue rejection, bone marrow rejection, organ transplant rejection, graft versus host disease, psoriasis, chronic obstructive pulmonary disease, asthma, and atherosclerosis, rheumatoid arthritis, multiple sclerosis, Lupus erythematosus, Hashimoto's thyroiditis, primary mixedema, Graves' disease, pernicious anemia, autoimmune atrophic gastritis, insulin dependent diabetes mellitus, good pasture's syndrome, myasthenia gravis, pemphigus, Crohn's disease, sympathetic opthalmia, autoimmune uveitis, autoimmune hemolytic anemis, idiopathic thrombocytopenia, primary biliary cirrhosis, ulcerative colitis, Sjogren's syndrome, polymyositis, and mixed connective tissue disease.  
     
     
         13 . The method according to  claim 11 , wherein the pharmaceutical composition is co-administered with a pharmaceutical composition comprising an isolated fusion polypeptide consisting of amino acid sequence SEQ ID NO:9, and a physiologically acceptable carrier, diluent, or excipient.