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Mature CD4⁺ T Cells Perceive a Positively Selecting Class II MHC/Peptide Complex in the Periphery¹

Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912

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^bwt) diminished when transferred into mice with A^b covalently bound with a single peptide (A^bEp). Moreover, transfer of a mixture of naive CD4⁺ T cells derived from A^bwt and from A^bEp mice into A^bEp 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^bEp or A^bwt mice, these cells survived in both recipients for more than 4 wk, but further expanded in the A^bwt 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.

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