Induction of experimental autoimmune arthritis by a public epitope of the T cell receptor variable alpha domain of an arthritogenic T cell clone

T cell receptor (TCR) peptide immunizations have been demonstrated to prote ct against experimental autoimmune diseases. These findings have led to cli nical trials employing TCR peptides in multiple sclerosis and rheumatoid ar thritis patients. Previously, we identified a strongly immunogenic region o f the TCR alpha chain of an arthritogenic T cell clone (AV11 66-80). In thi s report, we show that rats immunized with AV11 66-80 developed arthritis w ith clinical symptoms and histology similar to adjuvant arthritis (AA). Tra nsfer of this disease into naive rats using AV11 66-80-specific T cells pro ved the T cell-mediated character of the disease. The AV11 66-80 arthritic rats developed resistance to Mycobacterium tuberculosis-induced AA, indicat ing that both forms of arthritis depended on similar regulatory mechanisms. This first demonstration of TCR peptide-induced arthritis, together with a n earlier report on a polymorphism in this very same AV11 66-80 region invo lved in arthritis resistance in mice, suggests a central role of the public epitope AV11 66-80 in the control of autoimmune arthritis. Although TCR pe ptide immunizations can be exploited to prevent experimental autoimmunity, caution should be taken in the induction of TCR peptide-specific T cells fo r immunotherapy to avoid adverse effects as shown here.