Functionally Diverse Human T Cells Recognize Non-microbial Antigens Presented by MR1

Overview

Journal Elife

Specialty Biology

Date 2017 May 19

PMID 28518056

Citations 91

Authors

Marco Lepore

Artem Kalinichenko

Salvatore Calogero

Pavanish Kumar

Bhairav Paleja

Mathias Schmaler

Vipin Narang

Francesca Zolezzi

Michael Poidinger

Lucia Mori

Gennaro De Libero

Affiliations

Soon will be listed here.

Abstract

MHC class I-related molecule MR1 presents riboflavin- and folate-related metabolites to mucosal-associated invariant T cells, but it is unknown whether MR1 can present alternative antigens to other T cell lineages. In healthy individuals we identified MR1-restricted T cells (named MR1T cells) displaying diverse TCRs and reacting to MR1-expressing cells in the absence of microbial ligands. Analysis of MR1T cell clones revealed specificity for distinct cell-derived antigens and alternative transcriptional strategies for metabolic programming, cell cycle control and functional polarization following antigen stimulation. Phenotypic and functional characterization of MR1T cell clones showed multiple chemokine receptor expression profiles and secretion of diverse effector molecules, suggesting functional heterogeneity. Accordingly, MR1T cells exhibited distinct T helper-like capacities upon MR1-dependent recognition of target cells expressing physiological levels of surface MR1. These data extend the role of MR1 beyond microbial antigen presentation and indicate MR1T cells are a normal part of the human T cell repertoire.

Citing Articles

Recognition of MR1-antigen complexes by TCR Vγ9Vδ2.

Loureiro J, Vacchini A, Berloffa G, Devan J, Schaefer V, Nosi V Front Immunol. 2025; 16:1519128.

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Dolton G, Thomas H, Tan L, Rius Rafael C, Doetsch S, Ionescu G J Clin Invest. 2025; 135(1).

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MR1 presents vitamin B6-related compounds for recognition by MR1-reactive T cells.

McInerney M, Awad W, Souter M, Kang Y, Wang C, Chan Yew Poa K Proc Natl Acad Sci U S A. 2024; 121(49):e2414792121.

PMID: 39589872 PMC: 11626183. DOI: 10.1073/pnas.2414792121.

Protective effect of TCR-mediated MAIT cell activation during experimental autoimmune encephalomyelitis.

Walkenhorst M, Sonner J, Meurs N, Engler J, Bauer S, Winschel I Nat Commun. 2024; 15(1):9287.

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Characterization of Tumor-Infiltrating Lymphocyte-Derived Atypical TCRs Recognizing Breast Cancer in an MR1-Dependent Manner.

Hayee A, Kobayashi E, Motozono C, Hamana H, My H, Okada T Cells. 2024; 13(20.

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