The role unconventional T cells play in protective immunity in humans is unclear. Mucosal-associated invariant T (MAIT) cells are an unconventional T cell subset restricted to the antigen-presenting molecule MR1. Here, we report the discovery of a patient homozygous for a rare Arg31His (R9H in the mature protein) mutation in MR1 who has a history of difficult-to-treat viral and bacterial infections. MR1^R9H was unable to present the potent microbially derived MAIT cell stimulatory ligand. The MR1^R9H crystal structure revealed that the stimulatory ligand cannot bind due to the mutation lying within, and causing structural perturbation to, the ligand-binding domain of MR1. While MR1^R9H could bind and be up-regulated by a MAIT cell inhibitory ligand, the patient lacked circulating MAIT cells. This shows the importance of the stimulatory ligand for MAIT cell selection in humans. The patient had an expanded γδ T cell population, indicating a compensatory interplay between these unconventional T cell subsets.

非常规T细胞在人类保护性免疫中的作用尚不清楚。黏膜相关不变 T (MAIT) 细胞是一种非常规的 T 细胞亚群，仅限于抗原呈递分子 MR1。在这里，我们报告了一名患者在 MR1 中发现了一种罕见的 Arg31His（成熟蛋白中的 R9H）突变，该患者有难以治疗的病毒和细菌感染史。MR1 ^R9H无法呈现有效的微生物衍生 MAIT 细胞刺激配体。MR1 ^R9H晶体结构显示刺激性配体不能结合，因为突变位于 MR1 的配体结合结构域内，并导致结构扰动。而MR1 ^R9H可以结合并被 MAIT 细胞抑制配体上调，患者缺乏循环 MAIT 细胞。这表明刺激配体对人类 MAIT 细胞选择的重要性。该患者的 γδ T 细胞群增加，表明这些非常规 T 细胞亚群之间存在补偿性相互作用。