Mature CD4+ T cells perceive a positively selecting class II MHC/peptide complex in the periphery

A repertoire of TCRs is selected in the thymus by interactions with MHC bound to self-derived peptides, Whether self peptides bound to MHC influence the survival of mature T cells in the periphery remains enigmatic. In this study, we show that the number of naive CD4(+) T cells that developed in mice with class II MHC bound with endogenous peptides (A(b)wt) diminished when transferred into mice with A(b) covalently bound with a single peptide (A(b)Ep). Moreover, transfer of a mixture of naive CD4(+) T cells derived from A(b)wt and from A(b)Ep mice into A(b)Ep mice resulted in the expansion of the latter and decline of the former. In contrast, when wild-type activated CD4(+) T cells were transferred into A(b)Ep or A(b)wt mice, these cells survived in both recipients for more than 4 wk, but further expanded in the A(b)wt host. We conclude that to survive, naive CD4(+) T cells favor peripheral expression of the class II MHC/peptide complex(es) involved in their thymic selection, whereas some of activated CD4(+) T cells may require them only for expansion.