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 pr otein, leads to collagen-induced arthritis (CIA), a model for rheumatoid ar thritis (RA). CIA symptoms consist of an erosive joint inflammation caused by an autoimmune attack, mediated by both T and B lymphocytes. CD4(+) alpha beta T cells play a central role in CIA, both by helping B cells to produc e anti-CII antibodies, and by interacting with other cells in the joints, e g macrophages. In H-2(q) Mice, most CII-specific CD4(+) T cells recognize t he CII(256-270) peptide presented on the major histocompatibility complex ( MHC) class II A(q) molecule. Post-translational modifications (hydroxylatio n 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 immun odominant 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 th e possibility that autoimmune disease may be caused by the creation of new epitopes by posttranslational modification of proteins under circumstances such as trauma, inflammation or ageing.