SPECIFICITY OF AN HLA-DRB1-ASTERISK-0401-RESTRICTED T-CELL RESPONSE TO TYPE-II COLLAGEN

A panel of HLA-DRB10401-restricted CD4(+) mouse T cell hybridomas spe cific for bovine type II collagen were generated from transgenic mice expressing the human HLA-DRA10101/-DRB1*0401 and CD4 molecules. The v ast majority recognized a single peptide determinant corresponding to residues 261-273 (CII 261-273). This determinant was rapidly defined b y the use of a predictive algorithm for peptide binding to DRB10401. CII 261-273 is conserved in bovine and human type II collagen and over laps with an important I-A(q)-restricted T cell determinant in mice wi th collagen-induced arthritis. This study demonstrates how HLA-DR and human CD4-transgenic mice can be used to identify a T cell epitope in a potential or candidate autoantigen.