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

Rangsima Reantragoon, Alexandra Corbett, Isaac G Sakala, Nicholas A Gherardin, John Barton Furness, Zhenjun Chen, Sidonia B G Eckle, Adam P Uldrich, Richard William Birkinshaw, Onisha Patel, Lyudmila Kostenko, Bronwyn Meehan, Katherine Kedzierska, Ligong Liu, David P Fairlie, Ted H Hansen, Dale I Godfrey, Jamie Rossjohn, James McCluskey, Lars Kjer-Nielsen

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292 Citations (Scopus)

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-CH(2)OH), 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 CD8alpha(+)CD8beta(-/lo), implying predominant expression of CD8alphaalpha homodimers. Tetramer-sorted MAIT cells displayed a T(H)1 cytokine phenotype upon antigen-specific activation. Similarly, mouse MR1-rRL-6-CH(2)OH tetramers detected CD4(+), CD4(-)CD8(-) and CD8(+) MAIT cells in Valpha19 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.
Original languageEnglish
Pages (from-to)2305 - 2320
Number of pages16
JournalJournal of Experimental Medicine
Volume210
Issue number11
DOIs
Publication statusPublished - 2013

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