Designing and maintaining the mature TCR repertoire: the continuum of self-peptide : self-MHC complex recognition

Peripheral T cell maintenance requires a survival signal delivered upon T c ell receptor (TCR)-major histocompatibility complex (MHC) molecule interact ion. Since self-peptides play a critical role in the intrathymic positive s election of the mature TCR repertoire, we hypothesized an equally important role in T cell persistence. We used mice with a normal expression of MHC c lass II molecules but a restricted self-peptide complexity (H-2M alpha(-/-) ) to show that an MHC class II-restricted T cell specificity that displays a deficient positive selection in the H-2M alpha(-/-) thymus shows an impai red persistence after adoptive transfer in H-2M alpha(-/-) recipients. Fina lly, a wild-type CD4(+) TCR repertoire is incompletely maintained in H-2M a lpha(-/-) recipients. These observations suggest that, similar to intrathym ic positive selection, the maintenance of the mature TCR repertoire relies on the recognition of self-peptide:self-MHC complexes.