DOMAINS OF THE TCR-BETA-CHAIN REQUIRED FOR EARLY THYMOCYTE DEVELOPMENT

The T cell receptor beta (TCR beta) chain controls the developmental t ransition from CD4(-)CD8(-) to CD4(+)8(+) thymocytes. We show that the extracellular constant region and the transmembrane region, but not t he variable domain or cytoplasmic tail of the TCR beta chain are requi red for this differentiation step. TCR beta mutant chains lacking the cytoplasmic tail can be found at the cell surface both in functional T CR/CD3 complexes and in a GPI-anchored monomeric form indicating that the cytoplasmic tail of the TCR beta chain functions as an ER retentio n signal. The concordance between cell surface expression of the mutan t chains as TCR/CD3 complexes and their capacity to mediate thymocyte differentiation supports the CD3 mediated feedback model in which preT CR/CD3 complexes control the developmental transition from CD4(-)CD8(- ) to CD4(+)CD8(+) thymocytes.