跨膜蛋白
细胞生物学
化学
跨膜结构域
领域(数学分析)
细胞
生物
生物物理学
生物化学
受体
数学分析
数学
作者
Elliot A. Philips,J Liu,Audun Kvalvaag,Alexander M. Mørch,Anna S. Tocheva,Charles Ng,Hong Liang,Ian M. Ahearn,Ruimin Pan,Christina C. Luo,Alexander Leithner,Zhihua Qin,Yong Zhou,Antonio García‐España,Adam Mor,Dan R. Littman,Michael L. Dustin,Jun Wang,Xiang‐Peng Kong
出处
期刊:Science immunology
[American Association for the Advancement of Science (AAAS)]
日期:2024-03-08
卷期号:9 (93)
标识
DOI:10.1126/sciimmunol.ade6256
摘要
Programmed cell death-1 (PD-1) is a potent immune checkpoint receptor on T lymphocytes. Upon engagement by its ligands, PD-L1 or PD-L2, PD-1 inhibits T cell activation and can promote immune tolerance. Antagonism of PD-1 signaling has proven effective in cancer immunotherapy, and conversely, agonists of the receptor may have a role in treating autoimmune disease. Some immune receptors function as dimers, but PD-1 has been considered monomeric. Here, we show that PD-1 and its ligands form dimers as a consequence of transmembrane domain interactions and that propensity for dimerization correlates with the ability of PD-1 to inhibit immune responses, antitumor immunity, cytotoxic T cell function, and autoimmune tissue destruction. These observations contribute to our understanding of the PD-1 axis and how it can potentially be manipulated for improved treatment of cancer and autoimmune diseases.
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