An endoplasmic reticulum retention function for the cytoplasmic tail of the human pre-T cell receptor (TCR) alpha chain: potential role in the regulation of cell surface pre-TCR expression levels

The Journal of Experimental Medicine
Yolanda R CarrascoM L Toribio

Abstract

The pre-T cell receptor (TCR), which consists of a TCR-beta chain paired with pre-TCR-alpha (pTalpha) and associated with CD3/zeta 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-alpha-pTalpha proteins into pre-T and mature T cell lines, we show here that the low surface expression of the human pre-TCR is pTalpha chain dependent. Particularly, the cytoplasmic domain of pTalpha is sufficient to reduce surface expression of a conventional TCR-alpha/beta to pre-TCR expression levels. Such reduced expression cannot be attributed to qualitative differences in the biochemical composition of the CD3/zeta modules associated with pre-TCR and TCR surface complexes. Rather, evidence is provided that the pTalpha 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 pTalpha is also observed to be predominantly ER localized. Finally, sequential truncations along the pTalpha cytoplasmic domain revealed that removal of the COOH-terminal 48 residues is sufficient to release a CD4-pTalp...Continue Reading

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Citations

Mar 1, 2002·Current Opinion in Immunology·Christine BorowskiHarald von Boehmer
Sep 11, 2002·Seminars in Immunology·Yolanda R CarrascoMaría L Toribio
Sep 6, 2001·The Journal of Experimental Medicine·D GibbonsA C Hayday
Jun 19, 2002·The Journal of Experimental Medicine·Maddalena PanigadaFabio Grassi
Feb 25, 2005·The Journal of Experimental Medicine·Pilar Delgado, Balbino Alarcón
Dec 2, 2011·PloS One·Sébastien WälchliJohanna Olweus
Nov 4, 2010·Proceedings of the National Academy of Sciences of the United States of America·Philippe SmeltyJulien S Fellah
Mar 20, 2008·European Journal of Immunology·Denise FerreraFabio Grassi
Sep 21, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·T FangC A Roman
Oct 24, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·A R RamiroM L Toribio
Apr 4, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jean-Francois BrodeurVibhuti P Dave
Feb 25, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Munehide NakatsugawaNaoto Hirano
May 10, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Bassam M BadranKaren E Willard-Gallo
Apr 13, 2011·Molecular Immunology·Luca OrlandoClaudia Giachino

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Methods Mentioned

BETA
transfections
transfection
PCR
FCS
immunoprecipitation
Confocal Microscopy
flow cytometry
glycosylation
transgenic

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