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Expression of a transgenic class II Ab gene confers susceptibility to collagen‐induced arthritis

1994; Wiley; Volume: 24; Issue: 7 Linguagem: Inglês

10.1002/eji.1830240736

1521-4141

Ulrica Brunsberg, Kenth Gustafsson, Liselotte Jansson, Erik Michaëlsson, Lars Ährlund‐Richter, Sven Pettersson, Ragnar Mattsson, Rikard Holmdahl,

Immunotherapy and Immune Responses

Abstract 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.