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Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells

Open access
Reantragoon, Rangsima, Corbett, Alexandra J., Sakala, Isaac G., Gherardin, Nicholas A., Furness, John B., Chen, Zhenjun, Eckle, Sidonia B.G., Uldrich, Adam P., Birkinshaw, Richard W., Patel, Onisha, Kostenko, Lyudmila, Meehan, Bronwyn, Kedzierska, Katherine, Liu, Ligong, Fairlie, David P., Hansen, Ted H., Godfrey, Dale I., Rossjohn, Jamie, McCluskey, James, Kjer-Nielsen, Lars·2013·Journal of Experimental Medicine

Abstract

Mucosal-associated invariant T cells (MAIT cells) express a semi-invariant T cell receptor (TCR) α-chain, TRAV1-2–TRAJ33, and are activated by vitamin B metabolites bound by the major histocompatibility complex (MHC)–related class I–like molecule, MR1. Understanding MAIT cell biology has been restrained by the lack of reagents to specifically identify and characterize these cells. Furthermore, the use of surrogate markers may misrepresent the MAIT cell population. We show that modified human MR1 tetramers loaded with the potent MAIT cell ligand, reduced 6-hydroxymethyl-8-d-ribityllumazine (rRL-6-CH2OH), specifically detect all human MAIT cells. Tetramer+ MAIT subsets were predominantly CD8+ or CD4−CD8−, although a small subset of CD4+ MAIT cells was also detected. Notably, most human CD8+ MAIT cells were CD8α+CD8β−/lo, implying predominant expression of CD8αα homodimers. Tetramer-sorted MAIT cells displayed a TH1 cytokine phenotype upon antigen-specific activation. Similarly, mouse MR1–rRL-6-CH2OH tetramers detected CD4+, CD4−CD8− and CD8+ MAIT cells in Vα19 transgenic mice. Both human and mouse MAIT cells expressed a broad TCR-β repertoire, and although the majority of human MAIT cells expressed TRAV1-2–TRAJ33, some expressed TRAJ12 or TRAJ20 genes in conjunction with TRAV1-2. Accordingly, MR1 tetramers allow precise phenotypic characterization of human and mouse MAIT cells and revealed unanticipated TCR heterogeneity in this population.

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Metadata

Authors
Reantragoon, R., Corbett, A. J., Sakala, I. G., Gherardin, N. A., Furness, J. B., Chen, Z., Eckle, S. B. G., Uldrich, A. P., Birkinshaw, R. W., Patel, O., Kostenko, L., Meehan, B., Kedzierska, K., Liu, L., Fairlie, D. P., Hansen, T. H., Godfrey, D. I., Rossjohn, J., McCluskey, J., & Kjer-Nielsen, L.
Venue
Journal of Experimental Medicine
Published
2013-10-07
Volume
210
Issue
11
Pages
2305-2320
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
OpenAlex
W2151505523
Cited by
589
References
5
FWCI
18.25
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells. https://app.cochat.ai/papers/10.1084/jem.20130958
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Reantragoon, R., Corbett, A. J., Sakala, I. G., Gherardin, N. A., Furness, J. B., Chen, Z., Eckle, S. B. G., Uldrich, A. P., Birkinshaw, R. W., Patel, O., Kostenko, L., Meehan, B., Kedzierska, K., Liu, L., Fairlie, D. P., Hansen, T. H., Godfrey, D. I., Rossjohn, J., McCluskey, J., & Kjer-Nielsen, L. (2013). Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells. Journal of Experimental Medicine. https://doi.org/10.1084/jem.20130958

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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