COLLAGEN-INDUCED ARTHRITIS IN MICE - SYNERGISTIC EFFECT OF ESCHERICHIA-COLI LIPOPOLYSACCHARIDE BYPASSES EPITOPE SPECIFICITY IN THE INDUCTION OF ARTHRITIS WITH MONOCLONAL-ANTIBODIES TO TYPE-II COLLAGEN

DBA/1 mice develop a chronic peripheral arthritis after immunization w ith type II collagen termed collagen-induced arthritis. We have locali zed the main arthritogenic determinants of CB11, a CNBr-generated arth ritogenic fragment of chick type II collagen (CII), using 3 smaller pe ptide fragments of CB11 generated by endoproteinase LysC, LysC1 (CII 1 24-290), LysC2 (CII 291-374) and LysC3 (CII 375-402) and a panel of mo noclonal antibodies (mAb) specific to CB11. MAb specific to the arthri togenic region of CB11 were also used to study the synergistic effect of E. coli lipopolysaccharide (LPS) on antibody-mediated arthritis in naive DBA/1 mice. LysC2 contained a minimum essential arthritogenic Fr agment of type II collagen: LysC2 induced arthritis by active immuniza tion, also, a combination of four mAb specific to LysC2 passively tran sferred arthritis to naive mice. A single i.p, injection of LPS (50 mu g/mouse) reduced the threshold values of the arthritogenic dose of mA b from 1 mg to 50 mu g/clone per mouse, and decreased the number of mA b required for inducing arthritis from 4 to 2 clones. These observatio ns suggest that LysC?, an 84 amino acid residue fragment, contains the main arthritogenic determinants within chick CB11. Importantly, LPS, a strong inducer of pro-inflammatory cytokines, negates the required m ultiple epitope specificity of autoantibodies in the passive transfer model and acts synergistically in the induction of arthritis by autoan tibody.