Novel complexes of types of mhc class ii that bind to collagen type ii peptides and their use on diagnosis and treatment

Abstract

Novel complexes of peptides from human collagen type II and types of MHC class II associated with rheumatoid arthritis are provided. There is also provided novel therapies and methods for diagnosis of rheumatoid arthritis.

1 . A complex of a human recombinant MEW class II protein fragment and a synthesized or recombinantly produced peptide of between 8 and 20 amino acids comprising at least 8 consecutive amino acid residues with a sequence present in one of SEQ ID NO(s): 25, 26, 27, 28, 29, 30, 31, 37, 38, 39, 40, 41, 42, 43, 44, 45, 47, and 48. 
     
     
         2 . The complex of  claim 1 , wherein said synthesized or recombinantly produced peptide consists of a sequence selected from SEQ ID NO(s): 25, 26, 27, 28, 29, 30, 31, 37, 38, 39, 40, 41, 42, 43, 44, 45, 47, and 48. 
     
     
         3 . The complex of  claim 1 , wherein said sequence is selected from SEQ ID NO(s): 30, 31, 45, 47, and 48 and wherein said peptide comprises at least one citrulline residue. 
     
     
         4 . A method for diagnosis of rheumatoid arthritis comprising the steps of
 1) obtaining a sample of T-cells from a patient,   2) contacting the sample comprising T-cells with the complex of  claim 1 ,   3) detecting the ability of the T-cells to become activated by the peptide or peptide-MHC complexes.   
     
     
         5 . A kit of parts comprising the complex of  claim 1 . 
     
     
         6 . The kit according to  claim 5  additionally comprising at least one cell culture vessel. 
     
     
         7 . The kit according to  claim 5  comprising means for detecting the expression of at least one protein selected from the group consisting of CD3, CD4, Foxp3, CD25, TNF alpha, interferon gamma, IL-17A, IL-17F, CD154, CD69, Ki 67, IL-2, IL-13, and IL-10. 
     
     
         8 . The kit according to  claim 7  where the means for detection is an antibody against said protein. 
     
     
         9 . The kit according to  claim 7  where the means for detection is a set of primers for RT-PCR. 
     
     
         10 . A method for treatment of rheumatoid arthritis comprising administering the complex of  claim 1  to a patient. 
     
     
         11 . A composition comprising the complex of  claim 1  and a pharmaceutically suitable additive, enhancer, preservative, adjuvant, stabilizer, or micelle component.