The Actin-Capping Protein Alpha-Adducin Is Required for T-Cell Costimulation
Alpha-adducin (Add1) is a critical component of the actin-spectrin network in erythrocytes, acting to cap the fast-growing, barbed ends of actin filaments, and recruiting spectrin to these junctions. Add1 is highly expressed in T cells, but its role in T-cell activation has not been examined. Using...
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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2019-11-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.02706/full |
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author | Timothy J. Thauland Humza A. Khan Manish J. Butte |
author_facet | Timothy J. Thauland Humza A. Khan Manish J. Butte |
author_sort | Timothy J. Thauland |
collection | DOAJ |
description | Alpha-adducin (Add1) is a critical component of the actin-spectrin network in erythrocytes, acting to cap the fast-growing, barbed ends of actin filaments, and recruiting spectrin to these junctions. Add1 is highly expressed in T cells, but its role in T-cell activation has not been examined. Using a conditional knockout model, we show that Add1 is necessary for complete activation of CD4+ T cells in response to low levels of antigen but is dispensable for CD8+ T cell activation and response to infection. Surprisingly, costimulatory signals through CD28 were completely abrogated in the absence of Add1. This study is the first to examine the role of actin-capping in T cells, and it reveals a previously unappreciated role for the actin cytoskeleton in regulating costimulation. |
first_indexed | 2024-12-13T14:57:03Z |
format | Article |
id | doaj.art-135cdd5a9a8c4b0b931bbee3940a5750 |
institution | Directory Open Access Journal |
issn | 1664-3224 |
language | English |
last_indexed | 2024-12-13T14:57:03Z |
publishDate | 2019-11-01 |
publisher | Frontiers Media S.A. |
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series | Frontiers in Immunology |
spelling | doaj.art-135cdd5a9a8c4b0b931bbee3940a57502022-12-21T23:41:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-11-011010.3389/fimmu.2019.02706487601The Actin-Capping Protein Alpha-Adducin Is Required for T-Cell CostimulationTimothy J. ThaulandHumza A. KhanManish J. ButteAlpha-adducin (Add1) is a critical component of the actin-spectrin network in erythrocytes, acting to cap the fast-growing, barbed ends of actin filaments, and recruiting spectrin to these junctions. Add1 is highly expressed in T cells, but its role in T-cell activation has not been examined. Using a conditional knockout model, we show that Add1 is necessary for complete activation of CD4+ T cells in response to low levels of antigen but is dispensable for CD8+ T cell activation and response to infection. Surprisingly, costimulatory signals through CD28 were completely abrogated in the absence of Add1. This study is the first to examine the role of actin-capping in T cells, and it reveals a previously unappreciated role for the actin cytoskeleton in regulating costimulation.https://www.frontiersin.org/article/10.3389/fimmu.2019.02706/fullT cellcytoskeletoncostimulationadducinactinimmune synapse |
spellingShingle | Timothy J. Thauland Humza A. Khan Manish J. Butte The Actin-Capping Protein Alpha-Adducin Is Required for T-Cell Costimulation Frontiers in Immunology T cell cytoskeleton costimulation adducin actin immune synapse |
title | The Actin-Capping Protein Alpha-Adducin Is Required for T-Cell Costimulation |
title_full | The Actin-Capping Protein Alpha-Adducin Is Required for T-Cell Costimulation |
title_fullStr | The Actin-Capping Protein Alpha-Adducin Is Required for T-Cell Costimulation |
title_full_unstemmed | The Actin-Capping Protein Alpha-Adducin Is Required for T-Cell Costimulation |
title_short | The Actin-Capping Protein Alpha-Adducin Is Required for T-Cell Costimulation |
title_sort | actin capping protein alpha adducin is required for t cell costimulation |
topic | T cell cytoskeleton costimulation adducin actin immune synapse |
url | https://www.frontiersin.org/article/10.3389/fimmu.2019.02706/full |
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