Control of immune ligands by members of a cytomegalovirus gene expansion suppresses natural killer cell activation
Control of immune ligands by members of a cytomegalovirus gene expansion suppresses natural killer cell activation
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DOI：
10.7554/elife.22206.001
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发表时间：
2017-02-10
期刊：
影响因子：
7.7
通讯作者：
Wilkinson, Gavin W. G.
中科院分区：
文献类型：
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作者：
Fielding, Ceri A.;Weekes, Michael P.;Wilkinson, Gavin W. G.
人类巨细胞病毒 (HCMV) US12 家族由 10 个顺序排列的基因 (US12-21) 组成，其功能特征尚不清楚。我们现在确定了四个成员的新型自然杀伤 (NK) 细胞逃避功能：US12、US14、US18 和 US20。使用系统的多重蛋白质组学方法来定量类似于 1300 个细胞表面和类似于 7200 个全细胞蛋白，我们证明 US12 家族选择性地靶向质膜蛋白，并在调节 NK 配体、粘附分子和细胞因子受体中发挥关键作用。 US18 和 US20 协同作用，抑制关键 NKp30 配体 B7-H6 的细胞表面表达，从而抑制 NK 细胞活化。因此，US12 家族被认为是免疫调节的主要新枢纽。
The human cytomegalovirus (HCMV) US12 family consists of ten sequentially arranged genes (US12-21) with poorly characterized function. We now identify novel natural killer (NK) cell evasion functions for four members: US12, US14, US18 and US20. Using a systematic multiplexed proteomics approach to quantify similar to 1300 cell surface and similar to 7200 whole cell proteins, we demonstrate that the US12 family selectively targets plasma membrane proteins and plays key roles in regulating NK ligands, adhesion molecules and cytokine receptors. US18 and US20 work in concert to suppress cell surface expression of the critical NKp30 ligand B7-H6 thus inhibiting NK cell activation. The US12 family is therefore identified as a major new hub of immune regulation.