Role of glycopeptide-specific T cells in collagen-induced arthritis: an example how post-translational modification of proteins may be involved in autoimmune disease.
Immunization of mice with type II collagen (CII), a cartilage-restricted protein, leads to collagen-induced arthritis (CIA), a model for rheumatoid arthritis (RA). CIA symptoms consist of an erosive joint inflammation caused by an autoimmune attack, mediated by both T and B lymphocytes. CD4+ alphabeta T cells play a central role in CIA, both by helping B cells to produce anti-CII antibodies, and by interacting with other cells in the joints, eg macrophages. In H-2q mice, most CII-specific CD4+ T cells recognize the CII(256-270) peptide presented on the major histocompatibility complex (MHC) class II Aq molecule. Post-translational modifications (hydroxylation and variable glycosylation) of the lysine residue at position 264 of CII generate at least four different T-cell determinants that are specifically recognized by distinct T-cell subsets. Most T cells recognize CII(256-270) glycosylated with the monosaccharide galactose, which is consequently immunodominant in CIA. Recent studies indicate that the arthritogenic T cells in CIA are glycopeptide-specific, suggesting that induction of self-tolerance may be rendered more difficult by glycosylation of CII. These data open the possibility that outoimmune disease may be caused by the creation of new epitopes by posttranslational modification of proteins under circumstances such as trauma, inflammation or ageing.
Corthay
A
A
Section for Medical Inflammation Research, Lund University, Sweden. Alexandre.Corthay@labmed.uio.no
Bäcklund
J
J
Holmdahl
R
R
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D024043:Collagen Type II; D004195:Disease Models, Animal; D006031:Glycosylation; D051379:Mice; D008811:Mice, Inbred DBA; D012680:Sensitivity and Specificity
D024043:Collagen Type II