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

GARNER LC., AMINI A., FITZPATRICK MEB., Lett MJ., Hess G., Filipowicz Sinnreich M., PROVINE NM., KLENERMAN P.

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.

DOI

10.1038/s41590-023-01575-1

Type

Journal article

Journal

Nature Immunology

Publication Date

14/08/2023

Addresses

Lucy Garner, University of Oxford, Nuffield Department of Medicine, Experimental Medicine Division, John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU, United Kingdom

Keywords

Immunology, Adaptive immunity, T cells, Innate-like T cells, MAIT cells, T cell receptor

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