MR1T cells are a recently found class of T cells that recognize antigens presented by the major histocompatibility complex-I–related molecule MR1 in the absence of microbial infection. The nature of the self-antigens that stimulate MR1T cells remains unclear, hampering our understanding of their physiological role and therapeutic potential. By combining genetic, pharmacological, and biochemical approaches, we found that carbonyl stress and changes in nucleobase metabolism in target cells promote MR1T cell activation. Stimulatory compounds formed by carbonyl adducts of nucleobases were detected within MR1 molecules produced by tumor cells, and their abundance and antigenicity were enhanced by drugs that induce carbonyl accumulation. Our data reveal carbonyl-nucleobase adducts as MR1T cell antigens. Recognizing cells under carbonyl stress allows MR1T cells to monitor cellular metabolic changes with physiological and therapeutic implications.

中文翻译：

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核碱基加合物结合 MR1 并刺激 MR1 限制性 T 细胞


MR1T 细胞是最近发现的一类 T 细胞，可以在没有微生物感染的情况下识别由主要组织相容性复合物 I 相关分子 MR1 呈递的抗原。刺激 MR1T 细胞的自身抗原的性质仍不清楚，这阻碍了我们对其生理作用和治疗潜力的理解。通过结合遗传、药理学和生化方法，我们发现靶细胞中的羰基应激和核碱基代谢的变化促进了 MR1T 细胞的激活。在肿瘤细胞产生的 MR1 分子中检测到由核碱基羰基加合物形成的刺激性化合物，并且诱导羰基积累的药物增强了它们的丰度和抗原性。我们的数据揭示了羰基-核碱基加合物作为 MR1T 细胞抗原。识别羰基应激下的细胞使 MR1T 细胞能够监测具有生理和治疗意义的细胞代谢变化。