GERMLINE-ENCODED IGG ANTIBODIES BIND MOUSE CARTILAGE IN-VIVO - EPITOPE-SPECIFIC AND IDIOTYPE-SPECIFIC BINDING AND INHIBITION

Autoantibodies specific for type-II collagen (CII) occur in mice and r ats with collagen-induced arthritis (CIA). The binding in vitro and in vivo of mouse monoclonal antibodies (MoAbs) specific for separate epi topes in CII have been investigated. Two-day-old mice were injected in traperitoneally (i.p.) with the anti-CII antibody CIID3 in both unlabe lled and biotinylated form. It was found that antibodies binding to th e same epitope in CII in vivo can inhibit others from binding in an ep itope-specific fashion. The binding in vivo and in vitio of anti-CII a ntibodies could be inhibited also by an anti-idiotypic rat antiserum p roduced against the D3 antibody. The anti-idiotypic antiserum inhibite d the binding of the antibody D3 and the idiotypically related antibod y C2. The cDNA's of anti-CII antibodies D3, C2, and F4 were sequenced and found to contain germline encoded V-genes, apparently without soma tic mutations. The variable heavy chain of D3 and C2 both expressed th e same VH rearrangement, confirming that they share idiotypes. This re port demonstrates that CII-specific germline-encoded IgG autoantibodie s bind specifically to normal cartilage in vivo via their combining si te.