THE ROLE OF THE T-CELL RECEPTOR IN POSITIVE AND NEGATIVE SELECTION OF DEVELOPING T-CELLS

Although immature thymocytes bearing many combinations of TCR α and β variable components are produced, by no means all of these combinations are expressed on the mature T cells of any given individual. The receptor repertoire of mature T cells is limited by two apparently contradictory processes that occur in the thymus, positive selection and clonal elimination. The paradoxical existence of these two processes has yet to be explained experimentally, although it can be accommodated by several hypotheses. Self tolerance is crucial to survival. Therefore, the immune system has evolved at least two methods of ensuring that αβ TCR-bearing T cells are not reactive to self, clonal elimination in the thymus and anergy induced in the periphery. We do not now understand completely why some self antigens induce tolerance by one mechanism or the other. We also do not know why some potentially autoimmune T cells slip through these two traps to escape and give rise, at a later date, to autoimmune disease.