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.

中文翻译：

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MAIT细胞抗原的效力和特异性的分子基础。

MR1呈递时，基于微生物核黄素的代谢物抗原可激活与粘膜相关的不变T（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。在这里，我们设计了20种衍生物，称为改变的代谢物配体（AML），以剖析不同抗原成分对人MAIT-MR1轴的影响。对MAIT T细胞抗原受体（TCR）-MR1-AML三元复合物的11种晶体结构进行分析以及生化和功能分析表明，MR1细胞表面上调受配体的核糖基和非核糖基成分以及疏水性的影响MR1-AML接口。AML的极性核糖基链通过MAIT TCR-MR1-AML相互作用三联体中的动态补偿相互作用强烈影响MAIT细胞的激活能力。我们定义了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了解。