The peptide ligands mediating positive selection in the thymus control T cell survival and homeostatic proliferation in the periphery

Positive selection to self-MHC/peptide complexes has long been Viewed as a device for skewing the T cell repertoire toward recognition of foreign pept ides presented by self-MHC molecules. Here, we provide evidence for an alte rnative possibility, namely, that the self-peptides controlling positive se lection in the thymus serve to maintain the longevity of mature T cells in the periphery. Surprisingly, when total T cell numbers are reduced, these s elf-ligands become overtly stimulatory and cause naive T cells to prolifera te and undergo homeostatic expansion.