Competitive Displacement of pTα by TCR-α During TCR Assembly Prevents Surface Coexpression of Pre-TCR and αβ TCR

摘要

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