CD2 and its ligands are involved in development and activation of MAIT cells.

IF 10.6 1区医学 Q1 IMMUNOLOGY

Journal of Experimental Medicine Pub Date : 2025-12-01 Epub Date: 2025-09-30 DOI:10.1084/jem.20250431

Kaiwen Zhu, Jiayu Dou, Bin Li, Jin Qian, Ming-Chao Zhong, Zhenghai Tang, Yan Lu, André Veillette

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引用次数: 0

Abstract

MAIT cells are innate-like T cells known for their semi-invariant TCR that recognizes vitamin B metabolites presented by MR1. While the involvement of TCR and cytokines in development and activation of MAIT cells is well documented, the contribution of co-receptors, including SLAM family receptors, remains poorly understood. This study revealed that CD2 and its ligands, CD48 in mice and CD58 in humans, were crucial for MAIT cell maturation and antigen-driven activation, but not for their responses to cytokines. Cis interactions of CD2 with its ligands on the same cell were essential for activation, with trans interactions contributing in some contexts. A natural subset of human MAIT cells lacking CD2 displayed reduced activation responses to antigen. Human CD48 recognized 2B4 rather than CD2, dampening TCR signal strength and activation of human MAIT cells. Thus, the interplay between CD2 and its ligands is pivotal for MAIT cell development and activation, highlighting potential approaches for treating human diseases implicating MAIT cells.

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CD2及其配体参与了MAIT细胞的发育和激活。

MAIT细胞是先天样T细胞，以其半不变TCR而闻名，该TCR识别MR1呈现的维生素B代谢物。虽然TCR和细胞因子参与了MAIT细胞的发育和激活，但包括SLAM家族受体在内的共受体的作用仍然知之甚少。这项研究表明，CD2及其配体（小鼠中的CD48和人类中的CD58）对MAIT细胞成熟和抗原驱动激活至关重要，但对它们对细胞因子的反应并不重要。CD2与其配体在同一细胞上的顺式相互作用是激活的必要条件，在某些情况下，反式相互作用也起作用。缺乏CD2的人MAIT细胞的自然亚群对抗原的激活反应降低。人类CD48识别2B4而不是CD2，抑制TCR信号强度和人类MAIT细胞的激活。因此，CD2及其配体之间的相互作用对于MAIT细胞的发育和激活至关重要，这突出了治疗与MAIT细胞有关的人类疾病的潜在方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Experimental Medicine 医学-免疫学

CiteScore

26.60

自引率

1.30%

发文量

189

审稿时长

3-8 weeks

期刊介绍： Since its establishment in 1896, the Journal of Experimental Medicine (JEM) has steadfastly pursued the publication of enduring and exceptional studies in medical biology. In an era where numerous publishing groups are introducing specialized journals, we recognize the importance of offering a distinguished platform for studies that seamlessly integrate various disciplines within the pathogenesis field. Our unique editorial system, driven by a commitment to exceptional author service, involves two collaborative groups of editors: professional editors with robust scientific backgrounds and full-time practicing scientists. Each paper undergoes evaluation by at least one editor from both groups before external review. Weekly editorial meetings facilitate comprehensive discussions on papers, incorporating external referee comments, and ensure swift decisions without unnecessary demands for extensive revisions. Encompassing human studies and diverse in vivo experimental models of human disease, our focus within medical biology spans genetics, inflammation, immunity, infectious disease, cancer, vascular biology, metabolic disorders, neuroscience, and stem cell biology. We eagerly welcome reports ranging from atomic-level analyses to clinical interventions that unveil new mechanistic insights.