HLA-DQ6/8 double transgenic mice develop auricular chondritis following type II collagen immunization: A model for human relapsing polychondritis

We have generated transgenic (tg) mice expressing HLA-DQ8 alpha beta (DQA1*0301/DQB*0302) or HLA-DQ6 alpha beta (DQA1*0103/DQB1*0601) molecules lacking endogenous murine class II expression (APO) to investigate the ability of these HLA class II to present type II collagen (CII) and induce collagen-induced arthritis. The DQ8 alpha beta tg mice responded strongly to CII, developing severe arthritis, while DQ6 alpha beta tg mice were nonresponsive to CII, The addition of the mixed haplotype DQ8 alpha 6 beta molecule did not significantly influence CII reactivity, To examine the interaction of DQ6 alpha beta and DQ8 alpha beta molecules in vivo, we generated double tg DQ6 alpha beta/8 alpha beta (A beta 0) mice expressing both the alpha- and beta-chains of DQ6 and DQ8 molecules by mating DQ6 alpha beta (A beta 0) and DQ8 alpha beta (A beta 0) tg mice. CII-immunized DQ6 alpha beta/8 alpha beta tg mice developed severe experimental polychondritis, exhibiting both polyarthritis and auricular chondritis, The clinical, serologic, and histologic manifestations of experimental polychondritis are similar to those symptoms in human relapsing polychondritis. The susceptibility of DQ6 alpha beta/8 alpha beta tg mice compared with resistance in the parental strains suggests that expression of both the DQ6 alpha beta and DQ8 alpha beta tgs, unique to the DQ6 alpha beta 8 alpha beta tg strain, is important in susceptibility to experimental polychondritis, The DQ6 alpha beta/8 alpha beta tg mice provide a model to investigate putative autoantigens and the mechanisms of pathogenesis involved in relapsing polychondritis as well as the influence of the expression of multiple HLA class II molecules on the disease process.