Metabolite-based T-cell immunity is emerging as a major player in antimicrobial immunity, autoimmunity, and cancer. Here, small-molecule metabolites were identified to be captured and presented by the major histocompatibility complex class-I-related molecule (MR1) to T cells, namely mucosal-associated invariant T cells (MAIT) and diverse MR1-restricted T cells. Both MR1 and MAIT are evolutionarily conserved in many mammals, suggesting important roles in host immunity. Rational chemical modifications of these naturally occurring metabolites, termed altered metabolite ligands (AMLs), have advanced our understanding of the molecular correlates of MAIT T cell receptor (TCR)-MR1 recognition. This review provides a generalized framework for metabolite recognition and modulation of MAIT cells.

基于代谢物的 T 细胞免疫正在成为抗菌免疫、自身免疫和癌症的主要参与者。在这里，小分子代谢物被确定为主要组织相容性复合物 I 类相关分子 (MR1) 捕获并呈递给 T 细胞，即粘膜相关不变 T 细胞 (MAIT) 和多种 MR1 限制性 T 细胞。MR1 和 MAIT 在许多哺乳动物中在进化上都是保守的，这表明它们在宿主免疫中发挥着重要作用。这些天然代谢物的合理化学修饰，称为改变的代谢物配体 (AML)，增进了我们对 MAIT T 细胞受体 (TCR)-MR1 识别的分子相关性的理解。本综述提供了 MAIT 细胞代谢物识别和调节的通用框架。