Structural insight into MR1-mediated recognition of the mucosal associated invariant T cell receptor.
Structural insight into MR1-mediated recognition of the mucosal associated invariant T cell receptor.
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DOI：
10.1084/jem.20112095
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发表时间：
2012-04-09
期刊：
影响因子：
--
通讯作者：
McCluskey J
中科院分区：
文献类型：
--
作者：
Reantragoon R;Kjer-Nielsen L;Patel O;Chen Z;Illing PT;Bhati M;Kostenko L;Bharadwaj M;Meehan B;Hansen TH;Godfrey DI;Rossjohn J;McCluskey J
晶体结构和诱变分析表明MAIT TCR-MR 1对接模式不同于NKT TCR-CD 1d对接模式。粘膜相关不变T（MAIT）细胞表达结合MHC I类分子（MR 1）的半不变αβ T细胞受体（TCR）。然而，MR 1识别MAIT TCR的分子基础尚不清楚。在这项研究中，我们展示了人Vα7.2Jα33-Vβ2 MAIT TCR的晶体结构。突变揭示了在由不同微生物来源刺激的不同人MAIT TCR之间MAIT TCR-MR 1相互作用的高度保守要求。MAIT TCR β链中的单个残基与MR 1相互作用，而不变的MAIT TCR α链通过少量残基控制特异性，这些残基在物种间保守，位于Vα-Jα区域内。突变的MR 1表明，只有两个残基，这是中央定位和相对两侧的抗原结合裂缝的MR 1，是必不可少的MAIT细胞活化。诱变数据与由MAIT TCR α链主导的位于中心的MAIT TCR-MR 1对接一致。这种候选对接模式与NKT TCR-CD 1d-抗原相互作用的模式形成对比，在NKT TCR-抗原相互作用中，NKT TCR的α和β链都需要在CD 1d的F′-口袋上方进行连接。
Crystal structure and mutagenesis analyses suggest a MAIT TCR–MR1 docking mode distinct from the NKT TCR-CD1d docking mode. Mucosal-associated invariant T (MAIT) cells express a semiinvariant αβ T cell receptor (TCR) that binds MHC class I–like molecule (MR1). However, the molecular basis for MAIT TCR recognition by MR1 is unknown. In this study, we present the crystal structure of a human Vα7.2Jα33-Vβ2 MAIT TCR. Mutagenesis revealed highly conserved requirements for the MAIT TCR–MR1 interaction across different human MAIT TCRs stimulated by distinct microbial sources. Individual residues within the MAIT TCR β chain were dispensable for the interaction with MR1, whereas the invariant MAIT TCR α chain controlled specificity through a small number of residues, which are conserved across species and located within the Vα-Jα regions. Mutagenesis of MR1 showed that only two residues, which were centrally positioned and on opposing sides of the antigen-binding cleft of MR1, were essential for MAIT cell activation. The mutagenesis data are consistent with a centrally located MAIT TCR–MR1 docking that was dominated by the α chain of the MAIT TCR. This candidate docking mode contrasts with that of the NKT TCR–CD1d-antigen interaction, in which both the α and β chain of the NKT TCR is required for ligation above the F′-pocket of CD1d.
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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
影响因子：
9.8
作者：
Hee, Chee Seng;Gao, Song;Ziegler, Andreas
通讯作者：
Ziegler, Andreas
DOI：
10.1084/jem.152.6.1709
发表时间：
1980-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gillis S;Watson J
通讯作者：
Watson J
DOI：
10.1107/s0907444994003112
发表时间：
1994-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
BAILEY, S
通讯作者：
BAILEY, S
DOI：
10.4049/jimmunol.1003254
发表时间：
2011-04-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Chua WJ;Kim S;Myers N;Huang S;Yu L;Fremont DH;Diamond MS;Hansen TH
通讯作者：
Hansen TH