Domains of the TCR(3-Chain Required for Early Thymocyte Development

Summary The T cell receptor (3 (TCR(3) chain controls the developmental transition from CD4-CD8- to CD4+8+thymocytes. We show that the extracellular constant region and the transmembrane region, but not the variable domain or cytoplasmic tail of the TCPq3 chain are required for this differentiation step. TCI<(3 mutant chains lacking the cytoplasmic tail can be found at the cell surface both in functional TCR/CD3 complexes and in a GPI-anchored monomeric form in- dicating that the cytoplasmic tail of the TCR(3 chain functions as an ER retention signal. The con- cordance between cell surface expression of the mutant chains as TCR/CD3 complexes and their capacity to mediate thymocyte differentiation supports the CD3 mediated feedback model in which preTCR/CD3 complexes control the developmental transition from CD4 CD8- to CD4+CD8 + thymocytes.