在一个纯合点突变的个体中缺失黏膜相关不变 T 细胞。
Absence of mucosal-associated invariant T cells in a person with a homozygous point mutation in .
机构信息
Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia.
出版信息
Sci Immunol. 2020 Jul 24;5(49). doi: 10.1126/sciimmunol.abc9492.
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 was unable to present the potent microbially derived MAIT cell stimulatory ligand. The MR1 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 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.
非传统 T 细胞在人类保护性免疫中所起的作用尚不清楚。黏膜相关不变 T（MAIT）细胞是一种局限于抗原呈递分子 MR1 的非常规 T 细胞亚群。在这里，我们报告了一名 MR1 纯合子罕见 Arg31His（成熟蛋白中的 R9H）突变患者的发现，该患者有治疗困难的病毒和细菌感染史。MR1 无法呈现强效的微生物衍生的 MAIT 细胞刺激配体。MR1 的晶体结构表明，由于突变位于 MR1 的配体结合域内并导致其结构扰动，因此刺激配体无法结合。虽然 MR1 可以与 MAIT 细胞抑制性配体结合并上调，但该患者缺乏循环 MAIT 细胞。这表明在人类中，刺激配体对 MAIT 细胞的选择很重要。该患者具有扩增的 γδ T 细胞群体，表明这些非常规 T 细胞亚群之间存在代偿性相互作用。
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