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 beta2-microglobulin (beta2M) 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 beta2M-/- mice, CD4(intermediate)CD8hi cells with high expression of alphabeta T cell receptor (TCRalphabeta) were identified as having been positively selected by MHC class I for development into mature CD8+ T cells. Activated CD4(int)CD8hi cells bearing intermediate rather than high amounts of TCR were present in both wild-type and beta2M-/- 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.