Influenza virus infection augments NK cell inhibition through reorganization of major histocompatibility complex class I proteins
Influenza virus infection augments NK cell inhibition through reorganization of major histocompatibility complex class I proteins
复制标题
DOI：
10.1128/jvi.00870-08
复制
发表时间：
2008-08-01
影响因子：
5.4
通讯作者：
Mandelboim, Ofer
中科院分区：
文献类型：
--
作者：
Achdout, Hagit;Manaster, Irit;Mandelboim, Ofer
自然杀伤（NK）细胞的杀伤作用受抑制性、共刺激性和激活性受体的调节。抑制性受体主要识别主要组织相容性复合体（MHC）I类分子，而激活性NK受体识别应激诱导的配体和病毒产物。因此，各种抑制性和活化性配体表达的变化将决定靶细胞是否被杀死或保护。在这里，我们证明了流感病毒感染后，两种NK抑制性受体KIR2DL1和LIR1与感染细胞的结合特异性增加。结合增加发生在流感病毒感染后不久，在NK活化受体NKp46对感染细胞的识别增加之前。我们还阐明了这种效应的机制，并表明，流感病毒感染后，MHC I类蛋白重新分布在细胞表面上，并积累在脂筏微区。这种重新分布允许NK抑制性受体更好地识别，从而增加对NK细胞攻击的抵抗力。相反，T细胞活性不受MHC I类蛋白的重新分布的影响。因此，我们在这里提出了一种新的机制，开发的流感病毒，抑制NK细胞的细胞毒性，通过重组的MHC I类蛋白的细胞表面。
The killing by natural killer (NK) cells is regulated by inhibitory, costimulatory, and activating receptors. The inhibitory receptors recognize mainly major histocompatibility complex (MHC) class I molecules, while the activating NK receptors recognize stress-induced ligands and viral products. Thus, changes in the expression of the various inhibitory and activating ligands will determine whether target cells will be killed or protected. Here, we demonstrate that after influenza virus infection the binding of the two NK inhibitory receptors, KIR2DL1 and the LIR1, to the infected cells is specifically increased. The increased binding occurs shortly after the influenza virus infection, prior to the increased recognition of the infected cells by the NK activating receptor, NKp46. We also elucidate the mechanism responsible for this effect and demonstrate that, after influenza virus infection, MHC class I proteins redistribute on the cell surface and accumulate in the lipid raft microdomains. Such redistribution allows better recognition by the NK inhibitory receptors and consequently increases resistance to NK cell attack. In contrast, T-cell activity was not influenced by the redistribution of MHC class I proteins. Thus, we present here a novel mechanism, developed by the influenza virus, of inhibition of NK cell cytotoxicity, through the reorganization of MHC class I proteins on the cell surface.