Abstract：
Mucosal-associated invariant T (MAIT) cells have a semi-invariant T-cell receptor that allows recognition of antigen in the context of the MHC class I-related (MR1) protein. Metabolic intermediates of the riboflavin synthesis pathway have been identified as MR1-restricted antigens with agonist properties. As riboflavin synthesis occurs in many bacterial species, but not human cells, it has been proposed that the main purpose of MAIT cells is antibacterial surveillance and protection. The majority of human MAIT cells secrete interferon-gamma (IFNg) upon activation, while some MAIT cells in tissues can also express IL-17. Given that MAIT cells are present in human barrier tissues colonized by a microbiome, MAIT cells must somehow be able to distinguish colonization from infection to ensure effector functions are only elicited when necessary. Importantly, MAIT cells have additional functional properties, including the potential to contribute to restoring tissue homeostasis by expression of CTLA-4 and secretion of the cytokine IL-22. A recent study provided compelling data indicating that the range of human MAIT cell functional properties is explained by plasticity rather than distinct lineages. This further underscores the necessity to better understand how different signals regulate MAIT cell function. In this review, we highlight what is known in regards to activating and inhibitory signals for MAIT cells with a specific focus on signals relevant to healthy and inflamed tissues. We consider the quantity, quality, and the temporal order of these signals on MAIT cell function and discuss the current limitations of computational tools to extrapolate which signals are received by MAIT cells in human tissues. Using lessons learned from conventional CD8 T cells, we also discuss how TCR signals may integrate with cytokine signals in MAIT cells to elicit distinct functional states.
摘要：
粘膜相关不变T(MAIT)细胞具有半不变T细胞受体,其允许在MHCI类相关(MR1)蛋白的背景下识别抗原。核黄素合成途径的代谢中间体已被鉴定为具有激动剂性质的MR1限制性抗原。由于核黄素合成发生在许多细菌物种中，但不是人类细胞，有人提出MAIT细胞的主要目的是抗菌监测和保护。大多数人MAIT细胞在激活后分泌干扰素-γ（IFNg），而组织中的一些MAIT细胞也可以表达IL-17。鉴于MAIT细胞存在于由微生物组定植的人类屏障组织中，MAIT细胞必须以某种方式能够区分定植与感染，以确保仅在必要时才引起效应子功能。重要的是,MAIT细胞具有额外的功能特性，包括通过CTLA-4的表达和细胞因子IL-22的分泌有助于恢复组织稳态的潜力。最近的一项研究提供了令人信服的数据，表明人类MAIT细胞功能特性的范围是通过可塑性而不是不同的谱系来解释的。这进一步强调了更好地理解不同信号如何调节MAIT细胞功能的必要性。在这次审查中,我们重点介绍了MAIT细胞的激活和抑制信号，特别关注与健康和发炎组织相关的信号。我们考虑数量，质量,以及这些信号在MAIT细胞功能上的时间顺序，并讨论计算工具的当前局限性，以推断哪些信号被人体组织中的MAIT细胞接收。利用从传统CD8T细胞中吸取的经验教训，我们还讨论了TCR信号如何与MAIT细胞中的细胞因子信号整合以引起不同的功能状态。
