Key Points Blockade of Ly49/MHC-I interactions by anti–MHC-I results in the activation of NK cells. IFN-γ produced by activated NK cells stimulates APC to produce IL-15. Activated NK and T cells markedly augment antiviral and antitumor immunity. Visual Abstract NK cells recognize MHC class I (MHC-I) Ags via stochastically expressed MHC-I–specific inhibitory receptors that prevent NK cell activation via cytoplasmic ITIM. We have identified a pan anti–MHC-I mAb that blocks NK cell inhibitory receptor binding at a site distinct from the TCR binding site. Treatment of unmanipulated mice with this mAb disrupted immune homeostasis, markedly activated NK and memory phenotype T cells, enhanced immune responses against transplanted tumors, and augmented responses to acute and chronic viral infection. mAbs of this type represent novel checkpoint inhibitors in tumor immunity, potent tools for the eradication of chronic infection, and may function as adjuvants for the augmentation of the immune response to weak vaccines.

中文翻译：

---

前沿：抑制 NK 抑制性受体与 MHC I 类增强抗病毒和抗肿瘤免疫的相互作用

关键点 通过抗 MHC-I 阻断 Ly49/MHC-I 相互作用导致 NK 细胞活化。活化的 NK 细胞产生的 IFN-γ 刺激 APC 产生 IL-15。活化的 NK 和 T 细胞显着增强抗病毒和抗肿瘤免疫。Visual Abstract NK 细胞通过随机表达的 MHC-I 特异性抑制性受体识别 MHC I 类 (MHC-I) Ags，这些受体通过细胞质 ITIM 阻止 NK 细胞活化。我们已经鉴定了一种泛抗 MHC-I mAb，它可以在与 TCR 结合位点不同的位点阻断 NK 细胞抑制性受体的结合。用这种 mAb 治疗未经处理的小鼠会破坏免疫稳态，显着激活 NK 和记忆表型 T 细胞，增强对移植肿瘤的免疫反应，并增强对急性和慢性病毒感染的反应。