The different roles of MHC class recognition in thymocyte CD4 versus CD8 lineage commitment and positive selection

Commitment to the CD4+ or CD8+ T cell lineages and positive selection for full maturation of precursor T cells take place in the thymus. A detailed phenotypic analysis of differentiating thymocytes in normal and MHC-deficient mice has led to the identification of previously unappreciated subpopulations whose characteristics and dependence on major histocompatibility complex (MHC) class I versus class II molecule expression seem incompatible with a CD4/CD8 coreceptor-dependent 'instructional' model of thymocyte development. We suggest here that these and other recent data are most consistent with a model in which the TCR-mediated decision to enter the CD4 versus the CD8 lineage is independent of the class of MHC molecule recognized and is distinct from positive selection. This latter event appears to involve already lineage-committed cells and to require a match of the MHC class specificity of the lineage-defining, highly expressed CD4 or CD8 coreceptor and the TCR.