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 investigate this, T lymphocytes were studied in health and disease. The effect 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 residues and antigens. Subsequently, T cells in the autoimmune disease, multiple sclerosis, were studied, to investigate the mechanisms for breakdown in peripheral tolerance. T-cell clones that recognized both autoantigens 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 auto-antigen, were therefore studied in RA and an epitope successfully defined. The search for microbial 'mimics' triggering RA, and novel forms of immunotherapy are now possible--with potential rehabilitation of T cells.
Liverpool University, University Clinical Department at Aintree, Fazakerley Hospital.
R J
RJ
Moots
D017951:Antigen Presentation / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D003094:Collagen / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D018716:Molecular Mimicry; D013601:T-Lymphocytes / Q000276:immunology*
D001324:Autoantigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D003094:Collagen