POLYMORPHISM CONTRIBUTES TO H2-E-BETA-MEDIATED PROTECTION IN COLLAGEN-INDUCED ARTHRITIS

Collagen-induced arthritis (CIA) is an animal model of auto-immune inf lammatory polyarthritis which has features similar to rheumatoid arthr itis (RA). Much like RA, susceptibility to mouse CIA is influenced by the major histocompatibility complex (MHC) and is restricted to the H2 haplotypes cl and v. In previous experiments, we have found that the introduction of an H2-Eb(d) transgene in H2-A(q) CIA-susceptible mice was able to protect these mice against disease development, More recen tly, we have proposed that the polymorphism of the first domain of the E beta molecule modulates this protection, and that the presentation of a peptide from the third hypervariable region of the E beta chain b y the H2-A(q) molecule plays an important role in this mechanism. In t he present report, we investigated whether the H2-E-mediated protectio n is H2-A(q)-specific and whether the source of collagen has any influ ence. While the source of collagen had no effect on the protection, ou r results showed that the H2-E molecule failed to protect B1O.RIII (H2 (r)) mice against CIA. Further, the H2 haplotype r exerted a negative effect on the E beta(d)-mediated protection in H2-A(q)-restricted dise ase. Our results provide additional proof that self-MHC-derived peptid es, such as E beta peptides, may play an important role in the T-cell repertoire education and/or modulation of the T-cell response in the p eriphery.