EXPRESSION OF A TRANSGENIC CLASS-II AB GENE CONFERS SUSCEPTIBILITY TO COLLAGEN-INDUCED ARTHRITIS

The major histocompatibility complex (MHC) class II region is assumed to influence autoimmune diseases such as rheumatoid arthritis. In the mouse, the H-2(q) haplotype is associated with susceptibility to collagen-induced arthritis, while the H-2(p) haplotype is not. The class II A molecules of these haplotypes differ by only four amino acids in the first domain of the beta chain. To test if this difference accounts for the MHC influence on susceptibility to collagen-induced arthritis, H-2(p) mice were made transgenic with an Ab(p) gene altered to resemble the Ab(q) gene. The transgenic A(beta) chain hybridized with the A(alpha)(p) chain and was shown to be physiologically expressed by testing antigen-presentation capacity to A(q)-restricted T cell hybridomas and with FACS analyses. These transgenic mice developed an autoimmune response to type II collagen and also collagen-induced arthritis. The data unequivocally suggest the Ab gene as a major genetic susceptibility locus for autoimmune collagen-induced arthritis.