Published online 7 May 2001.
© The Rockefeller University Press, 0022-1007/2001/5/1045/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 9, May 7, 2001 1045-1058
An Endoplasmic Reticulum Retention Function for the Cytoplasmic Tail of the Human Pre–T Cell Receptor (Tcr)
Chain: Potential Role in the Regulation of Cell Surface Pre-Tcr Expression Levels
Yolanda R. Carrascoa,
Almudena R. Ramiroa,
César Triguerosa,
Virginia G. de Yébenesa,
Marina García-Peydróa, and
María L. Toribioa
a Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain
Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain.34-91-397-808734-91-397-8076
mtoribio{at}cbm.uam.es
The pre-T cell receptor (TCR), which consists of a TCR-β chain paired with pre–TCR-
(pT
) and associated with CD3/
components, is a critical regulator of T cell development. For unknown reasons, extremely low pre-TCR levels reach the plasma membrane of pre-T cells. By transfecting chimeric TCR-
–pT
proteins into pre-T and mature T cell lines, we show here that the low surface expression of the human pre-TCR is pT
chain dependent. Particularly, the cytoplasmic domain of pT
is sufficient to reduce surface expression of a conventional TCR-
/β to pre-TCR expression levels. Such reduced expression cannot be attributed to qualitative differences in the biochemical composition of the CD3/
modules associated with pre-TCR and TCR surface complexes. Rather, evidence is provided that the pT
cytoplasmic tail also causes a reduced surface expression of individual membrane molecules such as CD25 and CD4, which are shown to be retained in the endoplasmic reticulum (ER). Native pT
is also observed to be predominantly ER localized. Finally, sequential truncations along the pT
cytoplasmic domain revealed that removal of the COOH-terminal 48 residues is sufficient to release a CD4-pT
chimera from ER retention, and to restore native CD4 surface expression levels. As such a truncation in pT
also correlates with enhanced pre-TCR expression, the observed pT
ER retention function may contribute to the regulation of surface pre-TCR expression on pre-T cells.
Key Words: human pre–T cell receptor pT
cytoplasmic tail surface expression endoplasmic reticulum retention CD3 complex
C. Trigueros' present address is Imperial Cancer Research Fund, London WC2A 3PX, UK.
Abbreviations used in this paper: aa, amino acid(s); BCR, B cell receptor; Cyto, cytoplasmic; DN, double negative; DP, double positive; EC, extracellular; EGFP, enhanced green fluorescent protein; endo-H, endoglycosidase H; ER, endoplasmic reticulum; PDI, protein disulfide isomerase; pT
, pre–TCR-
; SP, single positive; TM, transmembrane.
© 2001 The Rockefeller University Press

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