ArticleThe Journal of experimental medicine2001
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.
Article in The Journal of experimental medicine, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 29 citations in OpenAlex.
- Genotypes truncating the intracellular tail of human pre-TCRα: From amorphic to isomorphic.Journal of human immunity · 2026Article
- Pre-TCR-targeted immunotherapy for T cell acute lymphoblastic leukemia.Nature immunology · 2025Article
- Pre-T cell receptor localization and trafficking are independent of its signaling.The Journal of cell biology · 2023Article
- Specific roles of each TCR hemichain in generating functional chain-centric TCR.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Pre-TCRα supports CD3-dependent reactivation and expansion of TCRα-deficient primary human T-cells.Molecular therapy. Methods & clinical development · 2014Article
- Article
- Identification of the pre-T-cell receptor alpha chain in nonmammalian vertebrates challenges the structure-function of the molecule.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- CSL-MAML-dependent Notch1 signaling controls T lineage-specific IL-7R{alpha} gene expression in early human thymopoiesis and leukemia.The Journal of experimental medicine · 2009Article
- An orderly inactivation of intracellular retention signals controls surface expression of the T cell antigen receptor.The Journal of experimental medicine · 2005Article
- Constitutive endocytosis and degradation of the pre-T cell receptor.The Journal of experimental medicine · 2002Article
- The biological activity of natural and mutant pTalpha alleles.The Journal of experimental medicine · 2001Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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-pTalpha chimera from ER retention, and to restore native CD4 surface expression levels. As such a truncation in pTalpha also correlates with enhanced pre-TCR expression, the observed pTalpha ER retention function may contribute to the regulation of surface pre-TCR expression on pre-T cells.
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