A FISTFUL OF T-CELLS

Evidence incriminating T cells in rheumatoid arthritis (RA) is strong but circumstantial-like a smoking gun at the scene of a crime. To inve stigate this, T lymphocytes were studied in health and disease. The ef fect of mutations in the groove of HLA-A2 on peptide presentation to T cells was studied to investigate normal T cell function. This allowed a detailed description of the interactions between individual MHC res idues and antigens. Subsequently, T cells in the autoimmune disease, m ultiple sclerosis, were studied, to investigate the mechanisms for bre akdown in peripheral tolerance. T-cell clones that recognized both aut oantigens and viral proteins were isolated, suggesting that infection may trigger disease. Autoantigens would need to be defined to use this strategy in RA. T-cell responses to type II collagen, a candidate aut o-antigen, were therefore studied in RA and an epitope successfully de fined. The search for microbial 'mimics' triggering RA, and novel form s of immunotherapy are now possible-with potential rehabilitation of T cells.