Role of TCR specificity in CD4 versus CD8 lineage commitment.

We have examined the role that TCR-alpha beta specificity plays in lineage commitment of thymocytes. Thymocytes in the process of selection have been distinguished by the expression of high levels of CD69 and CD5. The phenotype of most of these selected thymocytes is either CD4highCD8low or CD4lowCD8high, but some are CD4lowCD8low, a phenotype referred to as double-positive dull. Analysis of the phenotype of apoptotic thymocytes shows that double-positive dull cells make up many of the cells undergoing negative selection. Thymocytes from MHC class I- or class II-deficient mice and from MHC class I- and class II-restricted TCR transgenic mice have been analyzed for cells undergoing positive and negative selection. This analysis shows that the TCR specificity is a critical factor in the lineage determination of thymocytes, and any stochastic component to lineage commitment is minor.