IDENTIFICATION OF A CYANOGEN-BROMIDE FRAGMENT OF PORCINE TYPE-II COLLAGEN CAPABLE OF MODULATING COLLAGEN ARTHRITIS IN B10.RIII (H-2(R)) MICE

Previous studies directed towards identifying epitopes on type II coll agen (CII) important in collagen induced arthritis (CIA) in mice have focused primarily on responses mounted in susceptible H-2(q) strains. However, the nature of T and B cell responses against CII in susceptib le H-2(r) strains remains ill-defined. In an effort to identify region s on CII important in CIA in H-2(r) mice, we examined the cellular and humoral response of susceptible B10.RIII (H-2(r)) mice against cyanog en bromide (CB)cleaved fragments of porcine CII. Following immunizatio n with native porcine CII, LNC from B10.RIII mice mounted proliferativ e responses predominantly to peptide CB10, while negligible proliferat ion was detected against fragment CB9,7, CB8, CB11 or CB12. In contras t, sera from arthritic B10.RIII mice displayed a heterogeneous pattern of reactivity against porcine CII, with strong antibody binding measu red against the major fragments CB11, CB8 and CB10. To determine the i n vivo significance of the dominant cellular response to CB10, B10.RII I mice received an i.v. injection of soluble CB10 seven days before im munization with native procine CII. Mice pretreated with CB10 were hig hly resistant to CIA compared to control animals. Interestingly, B10. RIII mice pretreated with fragment CB11, a region of CII implicated in H-2(q)-restricted CIA, remained susceptible to arthritis induction. C ollectively, our findings indicate that the CB10 region of porcine C11 bears determinants which may be important in the induction and/or reg ulation of CIA in the H-2(r) haplotype.