T-cell death-inducing epitopes

Abstract

Cell death-inducing epitopes and polypeptides containing same. Also disclosed are compounds for inducing death of activated T-cells, a method of producing antibodies to the epitopes, a method of identifying compounds that bind to the epitopes, a method of inducing death of activated T-cells, and pharmaceutical compositions containing the compounds.

1 . A three-dimensional conformation of an isolated epitope represented by X 1 -X 2 -X 3 -X 4 -X 5 , wherein binding of a ligand to the epitope on activated T-cells induces death of the cells, and 
 X 1  is Tyr, Trp, His, or Met;    X 2  is Asp;    X 3  is Ser, Phe, Pro, Glu, or His;    X 4  is any amino acid; and    X 5  is Pro, Tyr, His, or Trp.    
     
     
         2 . An isolated polypeptide comprising X 1 -X 2 -X 3 -X 4 -X 5 , wherein binding of a ligand to the polypeptide on activated T-cells induces death of the cells, and 
 X 1  is Tyr, Trp, His, or Met;    X 2  is Asp;    X 3  is Ser, Phe, Pro, Glu, or His;    X 4  is any amino acid; and    X 5  is Pro, Tyr, His, or Trp.    
     
     
         3 . The polypeptide of  claim 2 , wherein the polypeptide is 5 to 1500 amino acids in length.  
     
     
         4 . The polypeptide of  claim 3 , wherein the polypeptide is 5 to 150 amino acids in length.  
     
     
         5 . The polypeptide of  claim 4 , wherein the polypeptide is 5 to 15 amino acids in length.  
     
     
         6 . The polypeptide of  claim 2 , wherein the polypeptide is selected from the group consisting of SEQ ID NOs:4 and 6-13.  
     
     
         7 . The polypeptide of  claim 2 , wherein the polypeptide is X 1 -X 2 -X 3 -X 4 -X 5 .  
     
     
         8 . An antibody that binds to an epitope having the three-dimensional conformation of  claim 1  and induces death of activated T-cells.  
     
     
         9 . The antibody of  claim 8 , wherein the antibody is monoclonal.  
     
     
         10 . A three-dimensional conformation of an isolated epitope represented by X 6 -X 7 -X 8 -X 9 -X 10 , wherein binding of a ligand to the epitope on activated T-cells induces death of the cells, and 
 X 6  is Asp;    X 7  is Tyr, Met, Asn, Trp, or Phe;    X 8  is Phe or Leu;    X 9  is Pro; and    X 10  is Glu.    
     
     
         11 . An isolated polypeptide comprising X 6 -X 7 -X 8 -X 9 -X 10 , wherein binding of a ligand to the polypeptide on activated T-cells induces death of the cells, and 
 X 6  is Asp;    X 7  is Tyr, Met, Asn, Trp, or Phe;    X 8  is Phe or Leu;    X 9  is Pro; and    X 10  is Glu.    
     
     
         12 . The polypeptide of  claim 11 , wherein the polypeptide is 5 to 1500 amino acids in length.  
     
     
         13 . The polypeptide of  claim 12 , wherein the polypeptide is 5 to 150 amino acids in length.  
     
     
         14 . The polypeptide of  claim 13 , wherein the polypeptide is 5 to 15 amino acids in length.  
     
     
         15 . The polypeptide of  claim 11 , wherein the polypeptide is selected from the group consisting of SEQ ID NOs:14-18.  
     
     
         16 . The polypeptide of  claim 11 , wherein the polypeptide is X 6 -X 7 -X 8 -X 9 -X 10 .  
     
     
         17 . An antibody that binds to an epitope having the three-dimensional conformation of  claim 10  and induces death of activated T-cells.  
     
     
         18 . The antibody of  claim 17 , wherein the antibody is monoclonal.  
     
     
         19 . A three-dimensional conformation of an isolated epitope represented by X 11 -X 12 -X 13 -X 14 , wherein binding of a ligand to the epitope on activated T-cells induces death of the cells, and 
 X 11  is Pro;    X 12  is Met;    X 13  is Glu or Ser; and    X 14  is Ile.    
     
     
         20 . An isolated polypeptide comprising X 11 -X 12 -X 13 -X 14 , wherein binding of a ligand to the polypeptide on activated T-cells induces death of the cells, and 
 X 11  is Pro;    X 12  is Met;    X 13  is Glu or Ser; and    X 14  is Ile.    
     
     
         21 . The polypeptide of  claim 20 , wherein the polypeptide is 4 to 1500 amino acids in length.  
     
     
         22 . The polypeptide of  claim 21 , wherein the polypeptide is 4 to 150 amino acids in length.  
     
     
         23 . The polypeptide of  claim 22 , wherein the polypeptide is 4 to 15 amino acids in length.  
     
     
         24 . The polypeptide of  claim 20 , wherein the polypeptide is selected from the group consisting of SEQ ID NOs: 20-22.  
     
     
         25 . The polypeptide of  claim 20 , wherein the polypeptide is X 11 -X 12 -X 13 -X 14 .  
     
     
         26 . An antibody that binds to an epitope having the three-dimensional conformation of  claim 19  and induces death of activated T-cells.  
     
     
         27 . The antibody of  claim 26 , wherein the antibody is monoclonal.