Homologous collagen‐induced arthritis in ratg and mice are associated with structurally different major histocompatibility complex DQ‐like molecules

Holmdahl, Rikard; Vingsbo, Carina; Hedrich, Hans; Karlsson, Mikael; Kvick, Christina; Goldschmidt, Tom J.; Gustafsson, Kenth

Collagen‐induced arthritis (CIA) in rats, induced with homologous type II collagen (CII), is a genetically more restricted disease and has better resemblance to rheumatoid arthritis by its chronic disease course, than CIA induced with heterologous CII. The DA strain is highly susceptible to CIA induced with homologous CII, while the Lewis strain is resistant. (DAxLew)F(1) is susceptible and backcrossing to Lewis reveals a close, but not complete, association of both arthritis and CII responsiveness to the RT1(a) haplotype. Analyses of congenic strains on DA and Lewis backgrounds suggest that expression of a major histocompatibility complex class II B(a) molecule, encoded from the RT1B(a) locus, is associated with arthritis susceptibility and CII responsiveness. The second exons coding for the first domains of the α and β chains of both the RT1(a) and RT1(1) haplotypes were sequenced and the deduced amino acid sequences compared with the corresponding molecule associated with susceptibility to CIA in the mouse (H‐2 A(q)). The sequences of the respective alleles revealed no obvious structural homology explaining the extensive similarities in the development of chronic autoimmune arthritis. Instead, this finding implies that different trimolecular constituents (i.e. class II,T cell receptor, and CII peptides) may yield an antigen presentation event that is able to trigger a similar autoaggressiveness in the two rodent species.