COLLAGEN-INDUCED ARTHRITIS IN B10.RIII MICE (H-2(R)) - IDENTIFICATIONOF AN ARTHRITOGENIC T-CELL DETERMINANT

Susceptibility to collagen-induced arthritis (CIA), a murine model of autoimmune arthritis, is strongly linked to only two major histocompat ibility complex (MHC) haplotypes, H-2(q) and H-2(r). In order to ident ify the determinants of type II collagen (CII) required to induce arth ritis in H-2(r)-bearing mice, B10.RIII mice were immunized with bovine , chick or human CII. Only bovine CII induced significant arthritis an d autoantibodies. When the major CNBr peptides of bovine collagen were isolated and used for immunization, only mice immunized with CB8, rep resenting CII 403-551, developed arthritis. To identify immunogenic ep itope(s) within CB8, a panel of synthetic peptides representing overla pping sequences of the bovine peptide was generated. When each peptide was cultured with T cells from B10.RIII mice immunized with CII, one peptide, representing CII 430-466, contained a major T-cell epitope. B y using an in vitro lymphokine production assay, the T-cell epitope wa s further narrowed to CII 442-456. These findings suggest that a T-cel l determinant important for the initiation of arthritis in B1O.RIII (H -2(r)) mice is located within a 15 amino acid sequence, residues 442-4 56 of bovine CII.