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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...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
1998
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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. |
format | Text |
id | pubmed-2212513 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1998 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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