TY - JOUR
T1 - Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells
AU - Reantragoon, Rangsima
AU - Corbett, Alexandra
AU - Sakala, Isaac G
AU - Gherardin, Nicholas A
AU - Furness, John Barton
AU - Chen, Zhenjun
AU - Eckle, Sidonia B G
AU - Uldrich, Adam P
AU - Birkinshaw, Richard William
AU - Patel, Onisha
AU - Kostenko, Lyudmila
AU - Meehan, Bronwyn
AU - Kedzierska, Katherine
AU - Liu, Ligong
AU - Fairlie, David P
AU - Hansen, Ted H
AU - Godfrey, Dale I
AU - Rossjohn, Jamie
AU - McCluskey, James
AU - Kjer-Nielsen, Lars
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
UR - http://www.ncbi.nlm.nih.gov/pubmed/24101382
U2 - 10.1084/jem.20130958
DO - 10.1084/jem.20130958
M3 - Article
VL - 210
SP - 2305
EP - 2320
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 11
ER -