The cytoplasmic domain of CD4 promotes the development of CD4 lineage T cells

doi:10.1084/jem.183.3.731

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The cytoplasmic domain of CD4 promotes the development of CD4 lineage T cells

A Itano, P Salmon, D Kioussis, M Tolaini, P Corbella and E Robey
Department of Molecular and Cell Biology, University of California, Berkeley, 94720, USA.

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 MHC, respectively, might influence the fate of uncommitted cells. Here we test the notion that intracellular signaling by CD4 directs the development of thymocytes to a CD4 lineage. A hybrid protein consisting of the CD8 extracellular and transmembrane domains and the cytoplasmic domain of CD4 (CD884) should bind class I MHC but deliver a CD4 intracellular signal. We find that expression of a hybrid CD884 protein in thymocytes of transgenic mice leads to the development of large numbers of class I MHC-specific, CD4 lineage T cells. We discuss these results in terms of current models for CD4 and CD8 lineage commitment.
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