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Article: Multiplex screening assay for identifying cytotoxic CD8+ T Cell Epitopes

TitleMultiplex screening assay for identifying cytotoxic CD8+ T Cell Epitopes
Authors
Keywordsinfluenza
Plasmodium
MERS
CD8 T cell
cytotoxicity
Issue Date2020
PublisherFrontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/immunology
Citation
Frontiers in Immunology, 2020, v. 11, p. article no. 400 How to Cite?
AbstractThe cytotoxicity of epitope-specific CD8+ T cells is usually measured indirectly through IFNγ production. Existing assays that directly measure this activity are limited mainly to measurements of up to two specificities in a single reaction. Here, we develop a multiplex cytotoxicity assay that allows direct, simultaneous measurement of up to 23 different specificities of CD8+ T cells in a single reaction. This can greatly reduce the amount of starting clinical materials for a systematic screening of CD8+ T cell epitopes. In addition, this greatly enhanced capacity enables the incorporation of irrelevant epitopes for determining the non-specific killing activity of CD8+ T cells, thereby allowing to measure the actual epitope-specific cytotoxicity activities. This technique is shown to be useful to study both human and mouse CD8+ T cells. Besides, our results from human PBMCs and three independent infectious animal models (MERS, influenza and malaria) further reveal that IFNγ expression by epitope-specific CD8+ T cells does not always correlate with their cell-killing potential, highlighting the need for using cytotoxicity assays in specific contexts (e.g., evaluating vaccine candidates). Overall, our approach opens up new possibilities for comprehensive analyses of CD8+ T cell cytotoxicity in a practical manner.
Persistent Identifierhttp://hdl.handle.net/10722/289542
ISSN
2019 Impact Factor: 5.085
2015 SCImago Journal Rankings: 2.810
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorPoh, CM-
dc.contributor.authorZheng, J-
dc.contributor.authorChannappanavar, R-
dc.contributor.authorChang, ZW-
dc.contributor.authorNguyen, THO-
dc.contributor.authorRénia, L-
dc.contributor.authorKedzierska, K-
dc.contributor.authorPerlman, S-
dc.contributor.authorPoon, LLM-
dc.date.accessioned2020-10-22T08:14:06Z-
dc.date.available2020-10-22T08:14:06Z-
dc.date.issued2020-
dc.identifier.citationFrontiers in Immunology, 2020, v. 11, p. article no. 400-
dc.identifier.issn1664-3224-
dc.identifier.urihttp://hdl.handle.net/10722/289542-
dc.description.abstractThe cytotoxicity of epitope-specific CD8+ T cells is usually measured indirectly through IFNγ production. Existing assays that directly measure this activity are limited mainly to measurements of up to two specificities in a single reaction. Here, we develop a multiplex cytotoxicity assay that allows direct, simultaneous measurement of up to 23 different specificities of CD8+ T cells in a single reaction. This can greatly reduce the amount of starting clinical materials for a systematic screening of CD8+ T cell epitopes. In addition, this greatly enhanced capacity enables the incorporation of irrelevant epitopes for determining the non-specific killing activity of CD8+ T cells, thereby allowing to measure the actual epitope-specific cytotoxicity activities. This technique is shown to be useful to study both human and mouse CD8+ T cells. Besides, our results from human PBMCs and three independent infectious animal models (MERS, influenza and malaria) further reveal that IFNγ expression by epitope-specific CD8+ T cells does not always correlate with their cell-killing potential, highlighting the need for using cytotoxicity assays in specific contexts (e.g., evaluating vaccine candidates). Overall, our approach opens up new possibilities for comprehensive analyses of CD8+ T cell cytotoxicity in a practical manner.-
dc.languageeng-
dc.publisherFrontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/immunology-
dc.relation.ispartofFrontiers in Immunology-
dc.rightsThis Document is Protected by copyright and was first published by Frontiers. All rights reserved. It is reproduced with permission.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectinfluenza-
dc.subjectPlasmodium-
dc.subjectMERS-
dc.subjectCD8 T cell-
dc.subjectcytotoxicity-
dc.titleMultiplex screening assay for identifying cytotoxic CD8+ T Cell Epitopes-
dc.typeArticle-
dc.identifier.emailPoon, LLM: llmpoon@hkucc.hku.hk-
dc.identifier.authorityPoon, LLM=rp00484-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3389/fimmu.2020.00400-
dc.identifier.pmid32218786-
dc.identifier.pmcidPMC7078160-
dc.identifier.scopuseid_2-s2.0-85082561031-
dc.identifier.hkuros317014-
dc.identifier.volume11-
dc.identifier.spagearticle no. 400-
dc.identifier.epagearticle no. 400-
dc.identifier.isiWOS:000525530200001-
dc.publisher.placeSwitzerland-
dc.identifier.issnl1664-3224-

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