MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage.
MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage.
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DOI：
10.1084/jem.20140507
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发表时间：
2014-07-28
期刊：
影响因子：
--
通讯作者：
Lewinsohn DM
中科院分区：
文献类型：
--
作者：
Gold MC;McLaren JE;Reistetter JA;Smyk-Pearson S;Ladell K;Swarbrick GM;Yu YY;Hansen TH;Lund O;Nielsen M;Gerritsen B;Kesmir C;Miles JJ;Lewinsohn DA;Price DA;Lewinsohn DM
MAIT细胞可以以克隆型依赖的方式区分病原体来源的配体，并且TCR库在个体中是不同的，这表明MAIT细胞库是由先前的微生物暴露形成的。粘膜相关的不变性T细胞（MAIT）表达一种半不变性T细胞受体（TCR），该受体检测由非多态性主要组织相容性复合体（MHC）样分子MR1呈现的微生物代谢物。MR1的高度保守性以及偏倚的MAIT TCRα链的使用被广泛认为表明在模式样识别系统中配体呈现和歧视有限。在这里，我们评估了MAIT细胞对三类微生物反应的TCR库。整个功能性MAIT细胞库中存在明显的多样性和异质性，特别是tcr - β链序列。此外，不同的病原体特异性反应以个体之间和个体内部不同的TCR使用为特征，这表明MAIT细胞适应是暴露于各种外源性mr1限制性表位的直接结果。与这一解释一致，具有不同tcr的MAIT细胞克隆对核黄素代谢物的反应不同。这些结果表明，MAIT细胞可以以克隆型依赖的方式区分病原体来源的配体，通过招募微生物暴露形成的特定谱，为适应性记忆提供了基础。
MAIT cells can discriminate between pathogen-derived ligands in a clonotype-dependent manner, and the TCR repertoire is distinct within individuals, indicating that the MAIT cell repertoire is shaped by prior microbial exposure. Mucosal-associated invariant T (MAIT) cells express a semi-invariant T cell receptor (TCR) that detects microbial metabolites presented by the nonpolymorphic major histocompatibility complex (MHC)–like molecule MR1. The highly conserved nature of MR1 in conjunction with biased MAIT TCRα chain usage is widely thought to indicate limited ligand presentation and discrimination within a pattern-like recognition system. Here, we evaluated the TCR repertoire of MAIT cells responsive to three classes of microbes. Substantial diversity and heterogeneity were apparent across the functional MAIT cell repertoire as a whole, especially for TCRβ chain sequences. Moreover, different pathogen-specific responses were characterized by distinct TCR usage, both between and within individuals, suggesting that MAIT cell adaptation was a direct consequence of exposure to various exogenous MR1-restricted epitopes. In line with this interpretation, MAIT cell clones with distinct TCRs responded differentially to a riboflavin metabolite. These results suggest that MAIT cells can discriminate between pathogen-derived ligands in a clonotype-dependent manner, providing a basis for adaptive memory via recruitment of specific repertoires shaped by microbial exposure.
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影响因子：
9.8
作者：
Martin E;Treiner E;Duban L;Guerri L;Laude H;Toly C;Premel V;Devys A;Moura IC;Tilloy F;Cherif S;Vera G;Latour S;Soudais C;Lantz O
通讯作者：
Lantz O
影响因子：
30.5
作者：
Le Bourhis, Lionel;Martin, Emmanuel;Lantz, Olivier
通讯作者：
Lantz, Olivier
DOI：
10.1084/jem.178.1.1
发表时间：
1993-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Porcelli S;Yockey CE;Brenner MB;Balk SP
通讯作者：
Balk SP
DOI：
10.1073/pnas.1222678110
发表时间：
2013-05-07
影响因子：
11.1
作者：
Lopez-Sagaseta, Jacinto;Dulberger, Charles L.;Adams, Erin J.
通讯作者：
Adams, Erin J.
影响因子：
9.8
作者：
Gold MC;Cerri S;Smyk-Pearson S;Cansler ME;Vogt TM;Delepine J;Winata E;Swarbrick GM;Chua WJ;Yu YY;Lantz O;Cook MS;Null MD;Jacoby DB;Harriff MJ;Lewinsohn DA;Hansen TH;Lewinsohn DM
通讯作者：
Lewinsohn DM