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by TCR- During TCR Assembly Prevents Surface Coexpression of Pre-TCR and 
TCR1
,
*
Department of Immunology, University of Toronto, Toronto, Ontario, Canada;
Department of Medicine, Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada;
Immunobiology Working Group, Division of Basic Sciences, Fox Chase Cancer Center, Philadelphia, PA 19111; and
PROCREA BioSciences Inc., Montreal, Quebec, Canada
During 
T cell development,
CD4-CD8- thymocytes first express pre-TCR
(pT/TCR-) before their differentiation to the
CD4+CD8+ stage. Positive selection of
self-tolerant T cells is then determined by the 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- by immature thymocytes terminates the surface
expression of pre-TCR. Our results reveal that expression of TCR-
precludes the formation of pT/TCR- 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
TCR expression on thymocytes undergoing selection is not compromised by
the expression of pre-TCR.
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