Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells.
Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells.
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DOI：
10.1084/jem.20130958
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发表时间：
2013-10-21
期刊：
影响因子：
--
通讯作者：
Kjer-Nielsen L
中科院分区：
文献类型：
--
作者：
Reantragoon R;Corbett AJ;Sakala IG;Gherardin NA;Furness JB;Chen Z;Eckle SB;Uldrich AP;Birkinshaw RW;Patel O;Kostenko L;Meehan B;Kedzierska K;Liu L;Fairlie DP;Hansen TH;Godfrey DI;Rossjohn J;McCluskey J;Kjer-Nielsen L
特异性染色MAIT细胞的负载抗原的MR 1四聚体的产生鉴定了人类和小鼠中表型和TCR库的异质性。粘膜相关不变T细胞（MAIT细胞）表达半不变T细胞受体（TCR）α链TRAV 1 -2-TRAJ 33，并被主要组织相容性复合体（MHC）相关I类分子MR 1结合的维生素B代谢物激活。了解MAIT细胞生物学一直受到缺乏特异性识别和表征这些细胞的试剂的限制。此外，使用替代标志物可能会错误地代表MAIT细胞群。我们表明，修饰的人MR 1四聚体装载有有效的MAIT细胞配体，还原6-羟甲基-8-d-核糖基鲁马嗪（rRL-6-CH 2 OH），特异性检测所有人MAIT细胞。四聚体+ MAIT亚群主要是CD 8+或CD 4 − CD 8 −，尽管也检测到一小部分CD 4 + MAIT细胞。值得注意的是，大多数人CD 8 + MAIT细胞是CD 8 α+ CD 8 β−/lo，这意味着主要表达CD 8 αα同源二聚体。四聚体分选的MAIT细胞在抗原特异性活化后显示TH 1细胞因子表型。同样，小鼠MR 1-rRL-6-CH 2 OH四聚体检测到Vα19转基因小鼠中的CD 4+、CD 4 − CD 8 −和CD 8 + MAIT细胞。人和小鼠MAIT细胞均表达广泛的TCR-β库，尽管大多数人MAIT细胞表达TRAV 1 -2-TRAJ 33，但一些表达TRAJ 12或TRAJ 20基因与TRAV 1 -2结合。因此，MR 1四聚体允许精确的人和小鼠MAIT细胞的表型表征，并揭示了该群体中的意外TCR异质性。
Generation of antigen-loaded MR1 tetramers that specifically stain MAIT cells identifies heterogeneity in phenotypes and TCR repertoires in humans and mice. 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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