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

✍ Scribed by Ulrica Brunsberg; Kenth Gustafsson; Liselotte Jansson; Erik Michaëlsson; Lars Ährlund-Richter; Sven Pettersson; Ragnar Mattsson; Rikard Holmdahl

• Book ID: 102824330
• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 604 KB
• Volume: 24
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.1830240736

✦ Synopsis

Expression of a transgenic class I1 Ab gene confers susceptibility to collagen-induced arthritis*

The major histocompatibility complex (MHC) class I1 region is assumed to influence autoimmune diseases such as rheumatoid arthritis. In the mouse, the H-24 haplotype is associated with susceptibility to collagen-induced arthritis, while the H-2P haplotype is not. The class I1 A molecules of these haplotypes differ by only four amino acids in the first domain of the f3 chain. To test if this difference accounts for the MHC influence on susceptibility to collagen-induced arthritis, H-2P mice were made transgenic with an AbP gene altered to resemble the Ab4 gene. The transgenic Ap chain hybridized with the A, P chain and was shown to be physiologically expressed by testing antigen-presentation capacity to Aq-restricted T cell hybridomas and with FACS analyses. These transgenic mice developed an autoimmune response to type I1 collagen and also collagen-induced arthritis. The data unequivocally suggest the Ab gene as a major genetic susceptibility locus for autoimmune collagen-induced arthritis.