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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Main Authors: Timothy J. Thauland, Humza A. Khan, Manish J. Butte
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-11-01
Series:Frontiers in Immunology
Subjects:
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.
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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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