Loyola University Chicago, Oncology Institute, 60153, Maywood, IL, USA.
Cell Mol Immunol. 2018 May;15(5):470-479. doi: 10.1038/cmi.2017.161. Epub 2018 Feb 5.
Natural killer group 2 member D (NKG2D) is a type II transmembrane receptor. NKG2D is present on NK cells in both mice and humans, whereas it is constitutively expressed on CD8 T cells in humans but only expressed upon T-cell activation in mice. NKG2D is a promiscuous receptor that recognizes stress-induced surface ligands. In NK cells, NKG2D signaling is sufficient to unleash the killing response; in CD8 T cells, this requires concurrent activation of the T-cell receptor (TCR). In this case, the function of NKG2D is to authenticate the recognition of a stressed target and enhance TCR signaling. CD28 has been established as an archetype provider of costimulation during T-cell priming. It has become apparent, however, that signals from other costimulatory receptors, such as NKG2D, are required for optimal T-cell function outside the priming phase. This review will focus on the similarities and differences between NKG2D and CD28; less well-described characteristics of NKG2D, such as the potential role of NKG2D in CD8 T-cell memory formation, cancer immunity and autoimmunity; and the opportunities for targeting NKG2D in immunotherapy.
自然杀伤细胞群 2 成员 D（NKG2D）是一种 II 型跨膜受体。NKG2D 存在于小鼠和人类的 NK 细胞上，而在人类的 CD8 T 细胞上持续表达，但仅在小鼠的 T 细胞激活时表达。NKG2D 是一种混杂受体，可识别应激诱导的表面配体。在 NK 细胞中，NKG2D 信号足以引发杀伤反应；在 CD8 T 细胞中，这需要同时激活 T 细胞受体（TCR）。在这种情况下，NKG2D 的功能是验证对受应激靶标的识别并增强 TCR 信号。CD28 已被确立为 T 细胞初始阶段提供共刺激的原型受体。然而，越来越明显的是，在初始阶段之外，其他共刺激受体（如 NKG2D）的信号对于最佳 T 细胞功能是必需的。本综述将重点讨论 NKG2D 和 CD28 之间的相似性和差异；NKG2D 不太为人所知的特征，例如 NKG2D 在 CD8 T 细胞记忆形成、癌症免疫和自身免疫中的潜在作用；以及在免疫治疗中靶向 NKG2D 的机会。
