近日，澳大利亚莫纳什大学Jamie Rossjohn、昆士兰大学David P. Fairlie和墨尔本大学 Alexandra J. Corbett研究组，合作揭示了维持黏膜相关恒定T（MAIT）细胞抗原效力和特异性的分子基础。3月2号的《自然—免疫学》在线发表了这项成果。

研究人员设计了20种衍生物并命名为改变的代谢物配体（AMLs），以了解不同抗原成分对人MAIT-MR1的影响。对MAIT T细胞抗原受体（TCR）-MR1-AML三元复合物11种晶体的结构以及生化和功能分析表明，MR1在细胞表面上调受配体核糖基和非核糖基组分以及MR1-AML接口疏水性的影响。

AML的极性核糖基链通过MAIT TCR–MR1–AML三联体间组分的动态相互作用强烈影响MAIT细胞的激活能力。该研究揭示了MAIT TCR可以差异识别AML的基础，从而提供了对MAIT细胞抗原特异性和效力的深入研究。

研究人员表示，MR1呈递时，微生物核黄素的代谢物抗原可激活与MAIT细胞。尚不清楚对有效抗原5-OP-RU的修饰如何影响MR1和MAIT细胞激活的呈递。

附：英文原文

Title: The molecular basis underpinning the potency and specificity of MAIT cell antigens

Author: Wael Awad, Geraldine J. M. Ler, Weijun Xu, Andrew N. Keller, Jeffrey Y. W. Mak, Xin Yi Lim, Ligong Liu, Sidonia B. G. Eckle, Jrme Le Nours, James McCluskey, Alexandra J. Corbett, David P. Fairlie, Jamie Rossjohn

Issue&Volume: 2020-03-02

Abstract: Mucosal-associated invariant T (MAIT) cells are activated by microbial riboflavin-based metabolite antigens when presented by MR1. How modifications to the potent antigen 5-OP-RU affect presentation by MR1 and MAIT cell activation remains unclear. Here we design 20 derivatives, termed altered metabolite ligands (AMLs), to dissect the impact of different antigen components on the human MAIT–MR1 axis. Analysis of 11 crystal structures of MAIT T cell antigen receptor (TCR)–MR1–AML ternary complexes, along with biochemical and functional assays, shows that MR1 cell-surface upregulation is influenced by ribityl and non-ribityl components of the ligand and the hydrophobicity of the MR1–AML interface. The polar ribityl chain of the AML strongly influences MAIT cell activation potency through dynamic compensatory interactions within a MAIT TCR–MR1–AML interaction triad. We define the basis by which the MAIT TCR can differentially recognize AMLs, thereby providing insight into MAIT cell antigen specificity and potency.

DOI: 10.1038/s41590-020-0616-6

Source: https://www.nature.com/articles/s41590-020-0616-6