NKG2D 配体在 NK 细胞激活中的双重功能。
A dual function of NKG2D ligands in NK-cell activation.
机构信息
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
出版信息
Eur J Immunol. 2012 Sep;42(9):2452-8. doi: 10.1002/eji.201141849. Epub 2012 Jul 27.
Abstract
NK-cell killing requires both the expression of activating receptor ligands and low MHC class I expression by target cells. Here we demonstrate that the expression of any of the murine ligands for the NK-cell activating receptor NKG2D results in a concomitant reduction in MHC class I expression. We show this both in tumor cell lines and in vivo. NK-cell lysis is enhanced by the decrease in MHC class I expression, suggesting the change is biologically relevant. These results demonstrate that NKG2D ligand expression on target cells not only allows for activating receptor recognition, but also actively reduces expression of the inhibitory ligand, MHC class I, leading to enhanced recognition and killing by NK cells.
摘要
自然杀伤 (NK) 细胞的杀伤作用既需要靶细胞表达激活受体配体，也需要靶细胞 MHC Ⅰ类分子的低表达。在此我们证明，表达 NK 细胞激活受体 NKG2D 的任何一种小鼠配体，都会导致 MHC Ⅰ类分子的表达同时减少。我们在肿瘤细胞系和体内都证明了这一点。NK 细胞的溶解作用因 MHC Ⅰ类分子表达的减少而增强，这表明这种变化具有生物学意义。这些结果表明，靶细胞上 NKG2D 配体的表达不仅允许激活受体识别，而且还主动降低抑制性配体 MHC Ⅰ类分子的表达，从而增强 NK 细胞的识别和杀伤作用。
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