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Interleukin 2–mediated Uncoupling of T Cell Receptor α/β from CD3 Signaling

T cell activation and clonal expansion is the result of the coordinated functions of the receptors for antigen and interleukin (IL)-2. The protein tyrosine kinase p56(lck) is critical for the generation of signals emanating from the T cell antigen receptor (TCR) and has also been demonstrated to pla...

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Autores principales: Haughn, Loralee, Leung, Bernadine, Boise, Lawrence, Veillette, André, Thompson, Craig, Julius, Michael
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1998
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212513/
https://www.ncbi.nlm.nih.gov/pubmed/9802969
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author Haughn, Loralee
Leung, Bernadine
Boise, Lawrence
Veillette, André
Thompson, Craig
Julius, Michael
author_facet Haughn, Loralee
Leung, Bernadine
Boise, Lawrence
Veillette, André
Thompson, Craig
Julius, Michael
author_sort Haughn, Loralee
collection PubMed
description T cell activation and clonal expansion is the result of the coordinated functions of the receptors for antigen and interleukin (IL)-2. The protein tyrosine kinase p56(lck) is critical for the generation of signals emanating from the T cell antigen receptor (TCR) and has also been demonstrated to play a role in IL-2 receptor signaling. We demonstrate that an IL-2–dependent, antigen-specific CD4(+) T cell clone is not responsive to anti-TCR induced growth when propagated in IL-2, but remains responsive to both antigen and CD3ε-specific monoclonal antibody. Survival of this IL-2–dependent clone in the absence of IL-2 was supported by overexpression of exogenous Bcl-xL. Culture of this clonal variant in the absence of IL-2 rendered it susceptible to anti-TCR–induced signaling, and correlated with the presence of kinase-active Lck associated with the plasma membrane. The same phenotype is observed in primary, resting CD4(+) T cells. Furthermore, the presence of kinase active Lck associated with the plasma membrane correlates with the presence of ZAP 70–pp21ζ complexes in both primary T cells and T cell clones in circumstances of responsive anti-TCR signaling. The results presented demonstrate that IL-2 signal transduction results in the functional uncoupling of the TCR complex through altering the subcellular distribution of kinase-active Lck.
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spelling pubmed-22125132008-04-16 Interleukin 2–mediated Uncoupling of T Cell Receptor α/β from CD3 Signaling Haughn, Loralee Leung, Bernadine Boise, Lawrence Veillette, André Thompson, Craig Julius, Michael J Exp Med Articles T cell activation and clonal expansion is the result of the coordinated functions of the receptors for antigen and interleukin (IL)-2. The protein tyrosine kinase p56(lck) is critical for the generation of signals emanating from the T cell antigen receptor (TCR) and has also been demonstrated to play a role in IL-2 receptor signaling. We demonstrate that an IL-2–dependent, antigen-specific CD4(+) T cell clone is not responsive to anti-TCR induced growth when propagated in IL-2, but remains responsive to both antigen and CD3ε-specific monoclonal antibody. Survival of this IL-2–dependent clone in the absence of IL-2 was supported by overexpression of exogenous Bcl-xL. Culture of this clonal variant in the absence of IL-2 rendered it susceptible to anti-TCR–induced signaling, and correlated with the presence of kinase-active Lck associated with the plasma membrane. The same phenotype is observed in primary, resting CD4(+) T cells. Furthermore, the presence of kinase active Lck associated with the plasma membrane correlates with the presence of ZAP 70–pp21ζ complexes in both primary T cells and T cell clones in circumstances of responsive anti-TCR signaling. The results presented demonstrate that IL-2 signal transduction results in the functional uncoupling of the TCR complex through altering the subcellular distribution of kinase-active Lck. The Rockefeller University Press 1998-11-02 /pmc/articles/PMC2212513/ /pubmed/9802969 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Haughn, Loralee
Leung, Bernadine
Boise, Lawrence
Veillette, André
Thompson, Craig
Julius, Michael
Interleukin 2–mediated Uncoupling of T Cell Receptor α/β from CD3 Signaling
title Interleukin 2–mediated Uncoupling of T Cell Receptor α/β from CD3 Signaling
title_full Interleukin 2–mediated Uncoupling of T Cell Receptor α/β from CD3 Signaling
title_fullStr Interleukin 2–mediated Uncoupling of T Cell Receptor α/β from CD3 Signaling
title_full_unstemmed Interleukin 2–mediated Uncoupling of T Cell Receptor α/β from CD3 Signaling
title_short Interleukin 2–mediated Uncoupling of T Cell Receptor α/β from CD3 Signaling
title_sort interleukin 2–mediated uncoupling of t cell receptor α/β from cd3 signaling
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212513/
https://www.ncbi.nlm.nih.gov/pubmed/9802969
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