Competitive displacement of pT alpha by TCR-alpha during TCR assembly prevents surface coexpression of pre-TCR and alpha beta TCR

During alpha beta T cell development, CD4(-)CD8(-) thymocytes first express pre-TCR (pT alpha /TCR-beta) before their differentiation to the CD4(+)CD8 (+) stage. Positive selection of self-tolerant T cells is then determined b y the alpha beta TCR expressed on CD4(+)CD8(+) thymocytes. Conceivably, an overlap in surface expression of these two receptors would interfere with t he delicate balance of thymic selection. Therefore, a mechanism ensuring th e sequential expression of pre-TCR and TCR must function during thymocyte d evelopment. In support of this notion, we demonstrate that expression of TC R-alpha by immature thymocytes terminates the surface expression of pre-TCR , Our results reveal that expression of TCR-alpha precludes the formation o f pT alpha /TCR-beta dimers within the endoplasmic reticulum, leading to th e displacement of pre-TCR from the cell surface. These findings illustrate a novel posttranslational mechanism for the regulation of pre-TCR expressio n, which may ensure that alpha beta TCR expression on thymocytes undergoing selection is not compromised by the expression of pre-TCR.