Development of mature CD8+ thymocytes: selection rather than instruction?

The role of major histocompatibility complex (MHC) molecules in T cell differentiation was investigated by comparison of thymocyte subpopulations in wild-type mice and beta 2-microglobulin (beta 2M) mutant mice deficient in MHC class I expression and mature CD8+ cells. On the basis of surface markers, glucocorticoid resistance, in vitro differentiation capacity, and absence in beta 2 M-l- mice, CD4intermediateCD8hi cells with high expression of alpha beta T cell receptor (TCR alpha beta) were identified as having been positively selected by MHC class I for development into mature CD8+ T cells. Activated CD4intCD8hi cells bearing intermediate rather than high amounts of TCR were present in both wild-type and beta 2M-l- animals. These data suggest that recognition of MHC class I molecules is required for full maturation to CD8+ T cells, but not for receptor-initiated commitment to the CD8+ lineage, consistent with a stochastic (selection) model of thymocyte development.