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.

中文翻译：

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跨膜结构域驱动的 PD-1 二聚体介导 T 细胞抑制

程序性细胞死亡-1 (PD-1) 是 T 淋巴细胞上的一种有效的免疫检查点受体。PD-1 与其配体 PD-L1 或 PD-L2 结合后，会抑制 T 细胞活化并促进免疫耐受。PD-1信号传导的拮抗剂已被证明在癌症免疫治疗中有效，相反，受体激动剂可能在治疗自身免疫性疾病中发挥作用。一些免疫受体以二聚体的形式发挥作用，但 PD-1 被认为是单体。在这里，我们证明 PD-1 及其配体由于跨膜结构域相互作用而形成二聚体，并且二聚化倾向与 PD-1 抑制免疫反应、抗肿瘤免疫、细胞毒性 T 细胞功能和自身免疫组织破坏的能力相关。这些观察结果有助于我们了解 PD-1 轴以及如何操纵它来改善癌症和自身免疫性疾病的治疗。