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

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 and Kjer-Nielsen, Lars (2013) Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells. Journal of Experimental Medicine, 210 11: 2305-2320. doi:10.1084/jem.20130958

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Author 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
Title Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells
Journal name Journal of Experimental Medicine   Check publisher's open access policy
ISSN 0022-1007
Publication date 2013-10-01
Year available 2013
Sub-type Article (original research)
DOI 10.1084/jem.20130958
Open Access Status File (Publisher version)
Volume 210
Issue 11
Start page 2305
End page 2320
Total pages 16
Place of publication New York, NY United States
Publisher Rockefeller University Press
Language eng
Abstract Mucosal-associated invariant T cells (MAIT cells) express a semi-invariant T cell receptor (TCR) alpha-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 CD8 alpha(+)CD8 beta(-/lo), implying predominant expression of CD8 alpha alpha homodimers. Tetramer-sorted MAIT cells displayed a T(H)1 cytokine phenotype upon antigen-specific activation. Similarly, mouse MR1-rRL-6-CH2OH tetramers detected CD4(+), CD4(-)CD8(-) and CD8(+) MAIT cells in V. 19 transgenic mice. Both human and mouse MAIT cells expressed a broad TCR-beta 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.
Keyword Vitamin B Metabolites
Mait Cells
Alpha Chain
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID AI046553
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 141 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 141 times in Scopus Article | Citations
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Created: Sun, 17 Nov 2013, 10:26:04 EST by System User on behalf of Institute for Molecular Bioscience