THE CYTOPLASMIC DOMAIN OF CD4 PROMOTES THE DEVELOPMENT OF CD4 LINEAGET-CELLS

Thymocytes must bind major histocompatibility complex (MHC) proteins o n thymic epithelial cells in order to mature into either CD8(+) cytoto xic T cells or CD4(+) helper T cells. Thymic precursors express both C D8 and CD4, and it has been suggested that the intracellular signals g enerated by CD8 or CD4 binding to class I or II MHC, respectively, mig ht influence the fate of uncommitted cells. Here we test the notion th at intracellular signaling by CD4 directs the development of thymocyte s to a CD4 lineage. A hybrid protein consisting of the CD8 extracellul ar and transmembrane domains and the cytoplasmic domain of CD4 (CD884) should bind class I MHC but deliver a CD4 intracellular signal. We fi nd that expression of a hybrid CD884 protein in thymocytes of transgen ic mice leads to the development of large numbers of class I MHC-speci fic, CD4 lineage T cells. We discuss these results in terms of current models for CD4 and CD8 lineage commitment.