SYSTEMIC VERSUS CARTILAGE-SPECIFIC EXPRESSION OF A TYPE-II COLLAGEN-SPECIFIC T-CELL EPITOPE DETERMINES THE LEVEL OF TOLERANCE AND SUSCEPTIBILITY TO ARTHRITIS

Immunization of mice with rat type II collagen (CII), a cartilage-spec ific protein, leads to development of collagen-induced arthritis (CIA) , a model for rheumatoid arthritis. To define the interaction between the immune system and cartilage, we produced two sets of transgenic mi ce. In the first we point mutated the mouse CII gene to express an ear lier defined T-cell epitope, CII-(256-270), present in rat CII. In the second we mutated the mouse type I collagen gene to express the same T-cell epitope. The mice with mutated type I collagen showed no T-cell reactivity to rat CLI and were resistant to CIA. Thus, the CII-(256-2 70) epitope is immunodominant and critical for development of CIA. In contrast, the mice with mutated CII had an intact B-cell response and had T cells which could produce gamma interferon, but not proliferate, in response to CII. They developed CIA, albeit with a reduced inciden ce. Thus, we conclude that T cells recognize CII derived from endogeno us cartilage and are partially tolerized but may still be capable of m ediating CIA.