AUTOANTIBODIES TO MURINE TYPE-II COLLAGEN IN COLLAGEN-INDUCED ARTHRITIS - A COMPARISON OF SUSCEPTIBLE AND NONSUSCEPTIBLE STRAINS

Collagen-induced arthritis (CIA) is an experimental autoimmune disease elicited in genetically susceptible strains of mice by immunization w ith heterologous type II collagen. This experimental disease is mediat ed by the immune response of both T cells and B cells, and susceptibil ity is restricted by the class II molecules of the MHC. In this study we identify specific epitopes bound by autoantibodies elicited through immunization of several haplotypes of C57BL/10 mice with chick alpha 1(II)-CB11. ELISA analysis using a panel of 15-mer murine type II coll agen peptides revealed a pattern of autoantibody epitope specificity t hat was remarkably similar among CIA-susceptible and nonsusceptible co ngenic strains, regardless of class II haplotype. However, one epitope was identified that was bound only by autoantibodies from CIA-suscept ible strains bearing I-A(q)(B10.Q and B10.Q beta BR). In addition, thi s epitope was also present within affinity-purified Ab obtained from t he CIA-susceptible strain DBA/1 (I-A(q)). Analyses of immune serum fro m B10.Q and B10.Q beta BR mice revealed that a subset of the antibodie s binding this epitope were of the IgG2 subclass, and therefore effici ent at fixing complement, a requirement for pathogenicity of the Abs i n CIA.