Understanding how signals are integrated to control natural killer (NK) cell responsiveness in the absence of antigen-specific receptors has been a challenge, but recent work has revealed some underlying principles that govern NK cell responses. NK cells use an array of innate receptors to sense their environment and respond to alterations caused by infections, cellular stress, and transformation. No single activation receptor dominates; instead, synergistic signals from combinations of receptors are integrated to activate natural cytotoxicity and cytokine production. Inhibitory receptors for major histocompatibility complex class I (MHC-I) have a critical role in controlling NK cell responses and, paradoxically, in maintaining NK cells in a state of responsiveness to subsequent activation events, a process referred to as licensing. MHC-I-specific inhibitory receptors both block activation signals and trigger signals to phosphorylate and inactivate the small adaptor Crk. These different facets of inhibitory signaling are incorporated into a revocable license model for the reversible tuning of NK cell responsiveness.

中文翻译：

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控制自然杀伤细胞反应：激活和抑制信号的整合。

了解在没有抗原特异性受体的情况下如何整合信号以控制自然杀伤 (NK) 细胞反应一直是一个挑战，但最近的工作揭示了一些控制 NK 细胞反应的基本原理。NK 细胞使用一系列先天受体来感知它们的环境并对感染、细胞压力和转化引起的变化做出反应。没有单一的激活受体占主导地位；相反，来自受体组合的协同信号被整合以激活天然细胞毒性和细胞因子的产生。主要组织相容性复合物 I 类 (MHC-I) 的抑制性受体在控制 NK 细胞反应和维持 NK 细胞对后续激活事件的反应状态方面具有关键作用，这一过程被称为许可。MHC-I 特异性抑制受体既能阻断激活信号，又能触发信号以磷酸化和灭活小接头 Crk。抑制信号的这些不同方面被纳入一个可撤销的许可模型，用于 NK 细胞反应性的可逆调整。