IDENTIFICATION AND CHARACTERIZATION OF A MAJOR TOLEROGENIC T-CELL EPITOPE OF TYPE-II COLLAGEN THAT SUPPRESSES ARTHRITIS IN B1O.RIII MICE

Tolerization of B10.RIII mice (G-2(r)) with intravenously injected typ e II collagen (CII) renders the animals resistant to induction of coll agen-induced arthritis (CIA). In order to clarify H-2(r)-restricted T- cell responses that modulate CIA, we have analysed the T-cell prolifer ative response of B10.RIII mice against cyanogen bromide (CB) peptides of CII, and detected the strongest response to alpha 1(II)-CB10 (CII 552-897). A panel of chemically synthesized overlapping peptide homolo gues was used to deduce the minimum structure of this determinant whic h was found to be CII 610-618. A 15-residue synthetic peptide flanking this region, CII 607-621, was found to effectively suppress arthritis when administered as a tolerogen. Collectively, these data identify t he structural component within alpha 1(II)-CB10 which is capable of in ducing tolerance in B10.RIII mice. A similar approach to the treatment of autoimmune arthritis, involving the institution of self-tolerance, has potential applicability to human rheumatoid arthritis.