Role of self-major histocompatibility complex/peptide ligands in selectionand maintenance of a diverse T cell repertoire

Positive selection has long been thought to be a devise for producing a rep ertoire of T cells that can efficiently recognize foreign peptides in the c ontext of self-major histocompatibility complex (MHC) molecules. However, i n the light of recent evidence that long-term survival of mature T cells re quires continuous contact with self-MHC molecules, the possibility for an a dditional role for positive selection has emerged: to generate a repertoire of T cells that can be maintained in the periphery through contact with se lf-MHC/ peptide ligands. In support of this idea, our recent work suggests that positive selection is highly peptide specific and, more important, tha t mature T cells require extrathymic contact with the same MHC/peptide liga nds that initially induced positive selection in the thymus in order for pr olonged survival and to undergo homeostatic proliferation in response to T cell deficiency.