o f CD 4 Lineage T Cells

Thymocytes must bind major histocompatibility complex (MHC) proteins on thymic epithelial cells in order to mature into either CD8 + cytotoxic T cells or CD4 + helper T cells. Thymic precursors express both CD8 and CD4, and it has been suggested that the intracellular signals generated by CD8 or CD4 binding to class I or II M H C , respectively, might influence the fate o f uncommitted cells. Here we test the notion that intracellular signaling by CD4 directs the development o f thymocytes to a CD4 lineage. A hybrid protein consisting o f the CD8 extracellular and transmembrane domains and the cytoplasmic domain o f CD4 (CD884) should bind class I M H C but deliver a CD4 intracellular signal. We find that expression o f a hybrid CD884 protein in thymocytes oftransgenic mice leads to the development o f large numbers o f class I MHC-specif ic, CD4 lineage T cells. We discuss these results in terms o f current models for CD4 and CD8 lineage commitment.