Volume 5 Supplement 3
Post-translational modification of type II collagen influences T-cell tolerance to self-type II collagen
© BioMed Central Ltd 2003
Published: 12 September 2003
T-cell response to type II collagen (CII) is essential in collagen-induced arthritis, a murine model of autoimmune arthritis. Collagen-induced arthritis is induced in mice by immunization with heterologous CII. However, T cells in these animals respond only to heterologous CII but not to homologous CII, suggesting T-cell tolerance to self-CII. In addition, we have found that the T-cell response to heterologous CII is also reduced in heterologous CII transgenic mice. In this study, we crossed the heterologous CII transgenic mice with anti-heterologous CII-specific TCR transgenic mice to verify the mechanism of T-cell tolerance to self-CII. Surprisingly, T cells in the TCR and heterologous CII double transgenic mice showed no evidence of tolerance. We found that the transgenic TCR recognizes the heterologous CII epitope only when lysine at position 266 is post-translationally hydroxylated. We also found CII prepared from the joint cartilage is dominated by the glycosylated form of lysine at position 266, which may result in the lack of T-cell tolerance in the TCR and heterologous CII double transgenic mice. These data imply the importance of post-translational modification of CII in the induction of T-cell tolerance to self-CII.