Development of a screening strategy for new modulators of T cell receptor signaling and T cell activation

Abstract Activation of the T cell receptor (TCR) leads to the generation of a network of signaling events critical to the developmental decision making and activation of T cells. Various experimental approaches continue to identify new signaling molecules, adaptor proteins, and other regulators of T...

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Main Authors:	Elijah W. Chen, Joanna Brzostek, Nicholas R. J. Gascoigne, Vasily Rybakin
Format:	Article
Language:	English
Published:	Nature Publishing Group 2018-07-01
Series:	Scientific Reports
Online Access:	https://doi.org/10.1038/s41598-018-28106-5

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spelling	doaj-dec67ebcd38c40508545f17c505764fa2020-12-08T05:40:05ZengNature Publishing GroupScientific Reports2045-23222018-07-01811910.1038/s41598-018-28106-5Development of a screening strategy for new modulators of T cell receptor signaling and T cell activationElijah W. Chen0Joanna Brzostek1Nicholas R. J. Gascoigne2Vasily Rybakin3Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of SingaporeDepartment of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of SingaporeDepartment of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of SingaporeDepartment of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of SingaporeAbstract Activation of the T cell receptor (TCR) leads to the generation of a network of signaling events critical to the developmental decision making and activation of T cells. Various experimental approaches continue to identify new signaling molecules, adaptor proteins, and other regulators of TCR signaling. We propose a screening strategy for the identification of small molecules affecting TCR signaling based on the uncoupling of TCR stimulation from cellular responses in developing thymocytes. We demonstrate that this strategy successfully identifies inhibitors of kinases already shown to act downstream of TCR engagement, as well as new inhibitors. The proposed strategy is easily scalable for high throughput screening and will contribute to the identification of new druggable targets in T cell activation.https://doi.org/10.1038/s41598-018-28106-5
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Elijah W. Chen Joanna Brzostek Nicholas R. J. Gascoigne Vasily Rybakin
spellingShingle	Elijah W. Chen Joanna Brzostek Nicholas R. J. Gascoigne Vasily Rybakin Development of a screening strategy for new modulators of T cell receptor signaling and T cell activation Scientific Reports
author_facet	Elijah W. Chen Joanna Brzostek Nicholas R. J. Gascoigne Vasily Rybakin
author_sort	Elijah W. Chen
title	Development of a screening strategy for new modulators of T cell receptor signaling and T cell activation
title_short	Development of a screening strategy for new modulators of T cell receptor signaling and T cell activation
title_full	Development of a screening strategy for new modulators of T cell receptor signaling and T cell activation
title_fullStr	Development of a screening strategy for new modulators of T cell receptor signaling and T cell activation
title_full_unstemmed	Development of a screening strategy for new modulators of T cell receptor signaling and T cell activation
title_sort	development of a screening strategy for new modulators of t cell receptor signaling and t cell activation
publisher	Nature Publishing Group
series	Scientific Reports
issn	2045-2322
publishDate	2018-07-01
description	Abstract Activation of the T cell receptor (TCR) leads to the generation of a network of signaling events critical to the developmental decision making and activation of T cells. Various experimental approaches continue to identify new signaling molecules, adaptor proteins, and other regulators of TCR signaling. We propose a screening strategy for the identification of small molecules affecting TCR signaling based on the uncoupling of TCR stimulation from cellular responses in developing thymocytes. We demonstrate that this strategy successfully identifies inhibitors of kinases already shown to act downstream of TCR engagement, as well as new inhibitors. The proposed strategy is easily scalable for high throughput screening and will contribute to the identification of new druggable targets in T cell activation.
url	https://doi.org/10.1038/s41598-018-28106-5
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Development of a screening strategy for new modulators of T cell receptor signaling and T cell activation

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