POSITIVE SELECTION OF V-BETA-8+CD4-8- THYMOCYTES BY CLASS-I MOLECULES EXPRESSED BY HEMATOPOIETIC-CELLS

A small subset of T cells of mature phenotype express the alpha/beta T cell receptor, but not CD4 and CD8 coreceptors (alpha/beta double-negative [DN] cells). The repertoire of Vbeta usage of alpha/beta DN cells is strongly biased towards Vbeta8 expression, suggesting that the formation of the population is subject to selection. We now report that deficiency of class I expression leads to a strongly depressed frequency of Vbeta8+ DN cells, but has little effect on Vbeta8- DN cells. Studies of hematopoietic chimeras between class I+ and class I- mice demonstrated that expression of class I molecules by hematopoietic cells is necessary and sufficient for selection of most Vbeta8 DN cells. The lack of a role for class I expression by thymic epithelial cells suggests that the mechanism of selection of these cells by class I differs significantly from the mechanism of selection of conventional T cells. Models to explain the selection of these cells as well as their possible function in vivo are discussed.