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...
Main Authors: | , , , , , , , |
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Format: | Journal article |
Language: | English |
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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. |
first_indexed | 2024-03-07T08:03:07Z |
format | Journal article |
id | oxford-uuid:1822a821-d889-4c24-a79b-631ee9206cc5 |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T08:03:07Z |
publishDate | 2023 |
publisher | Springer Nature |
record_format | dspace |
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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