Antigen specific activated T-lymphocytes, detection and use

Abstract

The invention concerns autoreactive peptides, peptide-MHC complexes, T cell subpopulations that react thereto as well as diagnostic and therapeutic applications of these compounds.

1 . An isolated complex which comprises: 
 (a) at least one peptide or derivative thereof and    (b) at least two MHC molecules or peptide-binding derivatives thereof, wherein said at least two MHC molecules or peptide-binding derivatives thereof are 
 (i) directly linked to each other, wherein said at least one peptide or derivative thereof is linked to at least one of said at least two MHC molecules or derivatives thereof, or  
 (ii) indirectly linked to each other via a direct or indirect link to said at least one peptide or derivative thereof.  
   
     
     
         2 . A complex which comprises a plurality of chemically coupled peptide or peptide derivative/MHC molecule or MHC molecule derivative complex monomers of  claim 1 .  
     
     
         3 . The complex of  claim 1 , wherein said at least one peptide or derivative thereof contains at least two MHC-binding regions and said at least two MHC molecules or derivatives thereof are bound to said peptide or derivative thereof via said MHC-binding regions.  
     
     
         4 . The complex of  claim 3 , wherein said at least two MHC-binding regions are indirectly linked to each other via an indirect link to said at least one peptide or derivative thereof and are separated from one another on the at least one peptide or derivative thereof by a spacer region.  
     
     
         5 . The complex of  claim 4 , wherein said spacer region comprises 10-15 amino acids.  
     
     
         6 . A complex which comprises a plurality of peptide or peptide derivative/MHC molecule or MHC molecule derivative complex monomers of  claim 1  that are linked to each other via antibodies.  
     
     
         7 . The complex of  claim 1 , wherein said MHC molecules are MHC class II molecules.  
     
     
         8 . The complex of  claim 7 , wherein said MHC class II molecules are selected from the group consisting of type DR3 and DR4.  
     
     
         9 . The complex of  claim 8 , wherein said MHC class II molecules are selected from the group consisting of subtype DR B1 0301 and DR B1 0401.  
     
     
         10 . The complex of  claim 1 , wherein said at least two MHC molecules or derivatives thereof are recombinant molecules.  
     
     
         11 . The complex of  claim 1 , which comprises at least one soluble peptide-binding MHC molecule derivative.  
     
     
         12 . The complex of  claim 1 , wherein said at least one peptide is an MHC molecule-binding peptide which is selected from the group consisting of SEQ ID NOS:2, 3 and 19-39; a fragment thereof that has at least 6 contiguous amino acids of SEQ ID NOS:2, 3 and 19-39; and a peptide that includes anchor positions for binding to MHC class II molecules DR3 or DR4, that binds to MHC molecules with specificity and affinity essentially equivalent to SEQ ID NOS:2, 3 and 19-39 and that is 6 to 25 amino acids in length, wherein said peptide or fragment thereof optionally is chemically derivatized.  
     
     
         13 . A composition which comprises a complex of  claim 1  in combination with a pharmaceutically acceptable carrier.  
     
     
         14 . The composition of  claim 13 , which further comprises an accessory stimulating component.  
     
     
         15 . The composition of  claim 14 , wherein said accessory stimulating component is selected from the group consisting of a cytokine, surface antigen B7, and both a cytokine and surface antigen B7.