[Idiotypic T-lymphocyte receptor in animal and human autoimmune diseases]

Animal models have demonstrated that the T-cell repertoire is restricted when the response to defined autoantigens is studied. Anti-V beta specific monoclonal antibodies or specific V beta-derived peptides can be used to manipulate autoreactive T-cells to either prevent or treat established experimental disease in animals. In some animal models of arthritis, inherited differences in the TCR repertoire can protect against the development of experimental autoimmune disease. Human studies have generally given conflicting results with regard to the role of the TCR complexes as susceptibility loci for disease. This may be due to the heterogeneity present in the human population and/or in the diseases studied. In some diseases, where there is convincing evidence for putative autoantigens (multiple sclerosis) or distinct immunodysfunctional pathology (hypergammaglobulinaemic primary Sjögren's syndrome), restricted TCR repertoires and germline TCR susceptibility loci can be discerned. Recent evidence suggests that autoimmune disease may eventually be mapped to regulatory regions of the TCR V genes rather than the allelic differences in coding region structure. This may have implications for the future therapy of autoimmune rheumatic disease.