MAIT細胞抗原有效性和特異性的分子基礎

MAIT細胞抗原有效性和特異性的分子基礎

作者：

小柯機器人

發布時間：2020/3/3 16:37:42

近日，澳大利亞莫納什大學Jamie Rossjohn、昆士蘭大學David P. Fairlie和墨爾本大學 Alexandra J. Corbett研究組，合作揭示了維持黏膜相關恆定T（MAIT）細胞抗原效力和特異性的分子基礎。3月2號的《自然—免疫學》在線發表了這項成果。

研究人員設計了20種衍生物並命名為改變的代謝物配體（AMLs），以了解不同抗原成分對人MAIT-MR1的影響。對MAIT T細胞抗原受體（TCR）-MR1-AML三元複合物11種晶體的結構以及生化和功能分析表明，MR1在細胞表面上調受配體核糖基和非核糖基組分以及MR1-AML接口疏水性的影響。

AML的極性核糖基鏈通過MAIT TCR–MR1–AML三聯體間組分的動態相互作用強烈影響MAIT細胞的激活能力。該研究揭示了MAIT TCR可以差異識別AML的基礎，從而提供了對MAIT細胞抗原特異性和效力的深入研究。

研究人員表示，MR1呈遞時，微生物核黃素的代謝物抗原可激活與MAIT細胞。尚不清楚對有效抗原5-OP-RU的修飾如何影響MR1和MAIT細胞激活的呈遞。

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