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⁺ αβ 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-2^q mice, most CII-specific CD4⁺ T cells recognize the CII(256-270) peptide presented on the major histocompatibility complex (MHC) class II A^q 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 imrnuno-dominant 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 autoimmune disease may be caused by the creation of new epitopes by post-translational modification of proteins under circumstances such as trauma, inflammation or ageing.