PROTECTIVE ROLE OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II EB(D) TRANSGENE ON COLLAGEN-INDUCED ARTHRITIS

Collagen-induced arthritis (CIA) is an animal model of autoimmune infl ammatory polyarthritis that has features similar to rheumatoid arthrit is (RA). Much like RA, susceptibility to mouse CIA is influenced by th e major histocompatibility complex (MHC), H-2, and restricted to the H -2(q) and H-2(r) haplotypes. Whereas the role of the H-2A molecule in susceptibility to CIA is well established, little is known about the r ole of H-2E molecule in the disease. In this study, we analyzed the ef fect of a transgenic E beta(d) molecule on CIA susceptibility in a rec ombinant mouse B10.RQB3, which expresses the CIA susceptible A(q) gene s and an Ea(k) gene, but does not produce an E molecule since Eb(q) is nonfunctional. In the presence of an Eb(d) transgene, a viable E mole cule is generated. Whereas B10.RQB3 were susceptible to CIA, B10.RQB3- E beta(d+) showed a dramatic reduction in the incidence of arthritis a s well as a decrease in the level of anti-mouse and anti-bovine CII an tibodies in their serum. No clear cut differences in the expression of T cell receptor (TCR) V beta was observed between E beta(d+) and E be ta(d-) transgenic mice. Mechanisms underlying the protective effect of E beta(d) transgenic molecule on CIA may shed light on how HLA-DR mol ecules influence human RA.