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Original Article

An Endoplasmic Reticulum Retention Function for the Cytoplasmic Tail of the Human Pre–T Cell Receptor (Tcr) Chain

Yolanda R. Carrasco^a, Almudena R. Ramiro^a, César Trigueros^a, Virginia G. de Yébenes^a, Marina García-Peydró^a, and María L. Toribio^a

^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

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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