Single-cell analysis of human MAIT cell transcriptional, functional and clonal diversity

Mucosal-associated invariant T (MAIT) cells are innate-like T cells that recognize microbial metabolites through a semi-invariant T cell receptor (TCR). Major questions remain regarding the extent of human MAIT cell functional and clonal diversity. To address these, we analyzed the single-cell trans...

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Main Authors: Garner, LC, Amini, A, Fitzpatrick, MEB, Lett, MJ, Hess, G, Filipowicz Sinnreich, M, Provine, NM, Klenerman, P
Format: Journal article
Language:English
Published: Springer Nature 2023
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author Garner, LC
Amini, A
Fitzpatrick, MEB
Lett, MJ
Hess, G
Filipowicz Sinnreich, M
Provine, NM
Klenerman, P
author_facet Garner, LC
Amini, A
Fitzpatrick, MEB
Lett, MJ
Hess, G
Filipowicz Sinnreich, M
Provine, NM
Klenerman, P
author_sort Garner, LC
collection OXFORD
description Mucosal-associated invariant T (MAIT) cells are innate-like T cells that recognize microbial metabolites through a semi-invariant T cell receptor (TCR). Major questions remain regarding the extent of human MAIT cell functional and clonal diversity. To address these, we analyzed the single-cell transcriptome and TCR repertoire of blood and liver MAIT cells and developed functional RNA-sequencing, a method to integrate function and TCR clonotype at single-cell resolution. MAIT cell clonal diversity was comparable to conventional memory T cells, with private TCR repertoires shared across matched tissues. Baseline functional diversity was low and largely related to tissue site. MAIT cells showed stimulus-specific transcriptional responses in vitro, with cells positioned along gradients of activation. Clonal identity influenced resting and activated transcriptional profiles but intriguingly was not associated with the capacity to produce IL-17. Overall, MAIT cells show phenotypic and functional diversity according to tissue localization, stimulation environment and clonotype.
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spelling oxford-uuid:1822a821-d889-4c24-a79b-631ee9206cc52023-10-13T06:12:19ZSingle-cell analysis of human MAIT cell transcriptional, functional and clonal diversityJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1822a821-d889-4c24-a79b-631ee9206cc5EnglishSymplectic ElementsSpringer Nature2023Garner, LCAmini, AFitzpatrick, MEBLett, MJHess, GFilipowicz Sinnreich, MProvine, NMKlenerman, PMucosal-associated invariant T (MAIT) cells are innate-like T cells that recognize microbial metabolites through a semi-invariant T cell receptor (TCR). Major questions remain regarding the extent of human MAIT cell functional and clonal diversity. To address these, we analyzed the single-cell transcriptome and TCR repertoire of blood and liver MAIT cells and developed functional RNA-sequencing, a method to integrate function and TCR clonotype at single-cell resolution. MAIT cell clonal diversity was comparable to conventional memory T cells, with private TCR repertoires shared across matched tissues. Baseline functional diversity was low and largely related to tissue site. MAIT cells showed stimulus-specific transcriptional responses in vitro, with cells positioned along gradients of activation. Clonal identity influenced resting and activated transcriptional profiles but intriguingly was not associated with the capacity to produce IL-17. Overall, MAIT cells show phenotypic and functional diversity according to tissue localization, stimulation environment and clonotype.
spellingShingle Garner, LC
Amini, A
Fitzpatrick, MEB
Lett, MJ
Hess, G
Filipowicz Sinnreich, M
Provine, NM
Klenerman, P
Single-cell analysis of human MAIT cell transcriptional, functional and clonal diversity
title Single-cell analysis of human MAIT cell transcriptional, functional and clonal diversity
title_full Single-cell analysis of human MAIT cell transcriptional, functional and clonal diversity
title_fullStr Single-cell analysis of human MAIT cell transcriptional, functional and clonal diversity
title_full_unstemmed Single-cell analysis of human MAIT cell transcriptional, functional and clonal diversity
title_short Single-cell analysis of human MAIT cell transcriptional, functional and clonal diversity
title_sort single cell analysis of human mait cell transcriptional functional and clonal diversity
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