Nondeletional pathways for the development of autoreactive thymocytes.

For some time, T cell receptor αβ (TCRαβ) signaling during thymocyte development was thought to induce one of three fates—negative selection to remove autoreactive cells, positive selection to enrich for host major histocompatibility complex (MHC)-restricted cells, and, in the absence of interactions with host MHC-peptides, death by neglect in experimental systems, negative selection is indeed found when thymocytes are presented with sufficient concentrations of their agonist antigen, that is, the same antigen that would activate them as mature T cells. In contrast, partial signaling mediated by variant peptides supports the positive selection of thymocytes, a step necessary for their lineage maturation into CD4 and CD8 T cells and exit from the thymus.