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 β 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_β chain hybridized with the A_α^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.