Rats or mice immunized with type II collagen (CII) develop a polyarthritis with histologic, clinical, and radiographic manifestations resembling those found in patients with rheumatoid arthritis. This immunologically mediated model appears to be T cell dependent. To characterize the pathogenic and immunoregulatory mechanisms involved in the induction of collagen-induced arthritis (CIA) CII-specific T cell lines, clones, and T-T hybridomas have been developed in the rat system. Selected T cell lines and clones are pathogenic in adoptive transfer studies. T-T hybridomas, derived from these arthritogenic CII-specific T cells, recognize a cyanogen bromide (CB) cleavage fragment CB11 (representing approximately 25% of the CII molecule) which in mouse CIA has the capacity to induce or, in a separate protocol, prevent CIA. The proposed studies will define the arthritogenic epitopes on CB fragments in the rat and mouse systems. A set of overlapping peptides from arthritogenic CB fragments will be synthesized. These will be used to identify and characterized the specific amino acid sequence(s) of the epitope(s). In parallel studies, CB fragments and synthetic epitopes will be evaluated in rats and mice for their capacity to induce neonatal tolerance. This could also lead to the identification of putative arthritogenic epitopes. Additional experiments will attempt to identify specific peptide determinants that might suppress the induction of adult CIA. If suppression were demonstrated, these peptides would be evaluated for their ability to arrest or reverse ongoing CIA (a system comparable to therapeutic interventions in rheumatoid arthritis). These studies should expand our understanding of T cell mediated immunoregulatory processes in the induction and prevention of an experimental autoimmune model of chronic inflammatory synovitis.
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