Eagle Robert A, Jafferji Insiya, Barrow Alexander D
University of Cambridge, Department of Pathology, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Cambridge, CB2 0XY, UK.
Curr Immunol Rev. 2009 Feb;5(1):22-34. doi: 10.2174/157339509787314369.
The activity of cytotoxic lymphocytes is regulated by the opposing function of stimulatory and inhibitory cell surface receptors. According to the now classical model of Natural Killer (NK) cell activity, the ligands for inhibitory receptors are constitutively expressed on healthy cells but can be lost on infection and on malignant cells. Loss of inhibitory checks will then allow activating signals to predominate, forming the basis of 'missing self recognition'. Natural Killer Group 2D (NKG2D) is an important member of the cohort of activating receptors expressed on Natural Killer (NK) cells and subsets of T cells. Ligands for the NKG2D receptor comprise a diverse array of self-proteins structurally related to MHC class I molecules. Expression of NKG2D ligands can be induced in cells during infection with pathogens, tumourigenesis, and by stimuli such as DNA damage, oxidative stress, and heat shock. Consequently NKG2D has been widely described as participating in 'stressed self' or 'damaged self' recognition. However, a body of evidence has recently emerged to suggest that this intuitive model of NKG2D function may be an oversimplification. NKG2D ligand expression has now widely been reported on cells that could not be described as stressed or damaged. For example activated T cells can express NKG2D ligands, and constitutive expression of NKG2D ligands has been reported on normal myelomonocytic cells, dendritic cells, and epithelial cells of the gut mucosa. In this article we will review the literature suggesting that NKG2D may function to recognise non-stressed cells and discuss the role NKG2D ligands could be playing in apparently healthy cells.
细胞毒性淋巴细胞的活性受刺激性和抑制性细胞表面受体的相反功能调节。根据目前经典的自然杀伤（NK）细胞活性模型，抑制性受体的配体在健康细胞上组成性表达，但在感染和恶性细胞上可能会丢失。抑制性检查的丧失将使激活信号占主导地位，形成“缺失自我识别”的基础。自然杀伤细胞2D（NKG2D）是在自然杀伤（NK）细胞和T细胞亚群上表达的激活受体群体的重要成员。NKG2D受体的配体包括一系列与MHC I类分子结构相关的自身蛋白。NKG2D配体的表达可在病原体感染、肿瘤发生期间以及受到DNA损伤、氧化应激和热休克等刺激时在细胞中诱导产生。因此，NKG2D被广泛描述为参与“应激自我”或“受损自我”识别。然而，最近出现了大量证据表明，这种直观的NKG2D功能模型可能过于简单化。现在广泛报道NKG2D配体在不能被描述为应激或受损的细胞上表达。例如，活化的T细胞可以表达NKG2D配体，并且在正常骨髓单核细胞、树突状细胞和肠道黏膜上皮细胞上已报道有NKG2D配体的组成性表达。在本文中，我们将回顾表明NKG2D可能具有识别非应激细胞功能的文献，并讨论NKG2D配体在明显健康的细胞中可能发挥的作用。
