POLYMORPHISM OF THE MHC CLASS-II EB GENE DETERMINES THE PROTECTION AGAINST COLLAGEN-INDUCED ARTHRITIS

Collagen-induced arthritis (CIA) is an animal model of auto immune pol yarthritis, sharing similarities with rheumatoid arthritis (RA). Parad oxally, susceptibility to mouse CIA is controlled by the H2A loci (De homologous) while RA is linked to HLA.DR genes (H2E homologous). We re cently showed that the E beta(d) molecule prevents CIA development in susceptible H2(q) mice. We addressed the question of whether H2Eb poly morphism will influence CIA incidence as HLA.DRB1 polymorphism does in RA. In F-1 mice, only H2Eb(d) and H2Eb(s) molecules showed protection . Using recombinant B10.RDD (Eb(d/b)) mice, we found that CIA protecti on was mediated by the first domain of the E beta(d) molecule. Using p eptides covering the third hypervariable region of the E beta chain, w e found a perfect correlation between presentation of E beta peptides by the H2A(q) molecule and protection on CIA. Therefore, the mechanism by which H2Eb protects against CIA seems to rely on the affinity of E beta peptides for the H2A(q) molecule.