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High-Affinity Ligands Can Trigger T Cell Receptor Signaling Without CD45 Segregation
How T cell receptors (TCRs) are triggered to start signaling is still not fully understood. It has been proposed that segregation of the large membrane tyrosine phosphatase CD45 from engaged TCRs initiates signaling by favoring phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAM...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5900011/ https://www.ncbi.nlm.nih.gov/pubmed/29686683 http://dx.doi.org/10.3389/fimmu.2018.00713 |
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author | Al-Aghbar, Mohammad Ameen Chu, Yeh-Shiu Chen, Bing-Mae Roffler, Steve R. |
author_facet | Al-Aghbar, Mohammad Ameen Chu, Yeh-Shiu Chen, Bing-Mae Roffler, Steve R. |
author_sort | Al-Aghbar, Mohammad Ameen |
collection | PubMed |
description | How T cell receptors (TCRs) are triggered to start signaling is still not fully understood. It has been proposed that segregation of the large membrane tyrosine phosphatase CD45 from engaged TCRs initiates signaling by favoring phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) in the cytoplasmic domains of CD3 molecules. However, whether CD45 segregation is important to initiate triggering is still uncertain. We examined CD45 segregation from TCRs engaged to anti-CD3 scFv with high or low affinity and with defined molecular lengths on glass-supported lipid bilayers using total internal reflection microscopy. Both short and elongated high-affinity anti-CD3 scFv effectively induced similar calcium mobilization, Zap70 phosphorylation, and cytokine secretion in Jurkat T cells but CD45 segregated from activated TCR microclusters significantly less for elongated versus short anti-CD3 ligands. In addition, at early times, triggering cells with both high and low affinity elongated anti-CD3 scFv resulted in similar degrees of CD3 co-localization with CD45, but only the high-affinity scFv induced T cell activation. The lack of correlation between CD45 segregation and early markers of T cell activation suggests that segregation of CD45 from engaged TCRs is not mandatory for initial triggering of TCR signaling by elongated high-affinity ligands. |
format | Online Article Text |
id | pubmed-5900011 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-59000112018-04-23 High-Affinity Ligands Can Trigger T Cell Receptor Signaling Without CD45 Segregation Al-Aghbar, Mohammad Ameen Chu, Yeh-Shiu Chen, Bing-Mae Roffler, Steve R. Front Immunol Immunology How T cell receptors (TCRs) are triggered to start signaling is still not fully understood. It has been proposed that segregation of the large membrane tyrosine phosphatase CD45 from engaged TCRs initiates signaling by favoring phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) in the cytoplasmic domains of CD3 molecules. However, whether CD45 segregation is important to initiate triggering is still uncertain. We examined CD45 segregation from TCRs engaged to anti-CD3 scFv with high or low affinity and with defined molecular lengths on glass-supported lipid bilayers using total internal reflection microscopy. Both short and elongated high-affinity anti-CD3 scFv effectively induced similar calcium mobilization, Zap70 phosphorylation, and cytokine secretion in Jurkat T cells but CD45 segregated from activated TCR microclusters significantly less for elongated versus short anti-CD3 ligands. In addition, at early times, triggering cells with both high and low affinity elongated anti-CD3 scFv resulted in similar degrees of CD3 co-localization with CD45, but only the high-affinity scFv induced T cell activation. The lack of correlation between CD45 segregation and early markers of T cell activation suggests that segregation of CD45 from engaged TCRs is not mandatory for initial triggering of TCR signaling by elongated high-affinity ligands. Frontiers Media S.A. 2018-04-09 /pmc/articles/PMC5900011/ /pubmed/29686683 http://dx.doi.org/10.3389/fimmu.2018.00713 Text en Copyright © 2018 Al-Aghbar, Chu, Chen and Roffler. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Al-Aghbar, Mohammad Ameen Chu, Yeh-Shiu Chen, Bing-Mae Roffler, Steve R. High-Affinity Ligands Can Trigger T Cell Receptor Signaling Without CD45 Segregation |
title | High-Affinity Ligands Can Trigger T Cell Receptor Signaling Without CD45 Segregation |
title_full | High-Affinity Ligands Can Trigger T Cell Receptor Signaling Without CD45 Segregation |
title_fullStr | High-Affinity Ligands Can Trigger T Cell Receptor Signaling Without CD45 Segregation |
title_full_unstemmed | High-Affinity Ligands Can Trigger T Cell Receptor Signaling Without CD45 Segregation |
title_short | High-Affinity Ligands Can Trigger T Cell Receptor Signaling Without CD45 Segregation |
title_sort | high-affinity ligands can trigger t cell receptor signaling without cd45 segregation |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5900011/ https://www.ncbi.nlm.nih.gov/pubmed/29686683 http://dx.doi.org/10.3389/fimmu.2018.00713 |
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