The herpesviral Fc receptor fcr-1 down-regulates the NKG2D ligands MULT-1 and H60.
The herpesviral Fc receptor fcr-1 down-regulates the NKG2D ligands MULT-1 and H60.
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疱疹病毒FC受体FCR-1下调了NKG2D配体MOULT-1和H60。
DOI：
10.1084/jem.20060514
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发表时间：
2006-08-07
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疱疹病毒α和β亚家族的成员编码的糖蛋白与免疫球蛋白(Ig)的Fc部分特异结合，质膜上驻留的疱疹病毒Fc受体似乎阻止病毒特异性Ig G激活抗体依赖的效应功能。我们发现，小鼠巨细胞病毒(MCMV)分子FCR-1促进NKG2D配体小鼠UL16结合蛋白样转录本(MULT)-1和H60从细胞表面快速下调。MCMV基因组中m138/FCR-1基因的缺失在体内以NKG2D依赖的方式减弱病毒对自然杀伤(NK)细胞的复制反应。在FCR-1胞外区和FCR-1跨膜区内需要一个不同的N末端模块来处理MULT-1以降解溶酶体。相反，H60的下调需要完整的FCR-1胞外结构域，这意味着FCR-1与NKG2D配体相互作用的独立模式。这些结果建立了一种新的病毒策略来下调NK细胞的反应，并突出了Fc受体功能的惊人多样性。
Members of the α- and β-subfamily of herpesviridae encode glycoproteins that specifically bind to the Fc part of immunoglobulin (Ig)G. Plasma membrane resident herpesviral Fc receptors seem to prevent virus-specific IgG from activating antibody-dependent effector functions. We show that the mouse cytomegalovirus (MCMV) molecule fcr-1 promotes a rapid down-regulation of NKG2D ligands murine UL16-binding protein like transcript (MULT)-1 and H60 from the cell surface. Deletion of the m138/fcr-1 gene from the MCMV genome attenuates viral replication to natural killer (NK) cell response in an NKG2D-dependent manner in vivo. A distinct N-terminal module within the fcr-1 ectodomain in conjunction with the fcr-1 transmembrane domain was required to dispose MULT-1 to degradation in lysosomes. In contrast, down-modulation of H60 required the complete fcr-1 ectodomain, implying independent modes of fcr-1 interaction with the NKG2D ligands. The results establish a novel viral strategy for down-modulating NK cell responses and highlight the impressive diversity of Fc receptor functions.