Human cytomegalovirus glycoprotein UL16 causes intracellular sequestration of NKG2D ligands, protecting against natural killer cell cytotoxicity.
Human cytomegalovirus glycoprotein UL16 causes intracellular sequestration of NKG2D ligands, protecting against natural killer cell cytotoxicity.
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DOI：
10.1084/jem.20022059
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发表时间：
2003-06-02
期刊：
影响因子：
--
通讯作者：
Cosman D
中科院分区：
文献类型：
--
作者：
Dunn C;Chalupny NJ;Sutherland CL;Dosch S;Sivakumar PV;Johnson DC;Cosman D
激活受体NKG2D表达在多种免疫效应细胞上，识别不同家族的主要组织相容性复合体(MHC)I类相关配体，包括MIC和ULBP蛋白。感染、应激或转化可诱导NKG2D配体的表达，导致效应细胞激活和杀伤表达配体的靶细胞。人巨细胞病毒(HCMV)膜糖蛋白UL16与人NKG2D的五个已知配体中的三个结合。UL16保留在细胞的内质网和顺式高尔基体中，并使MICB类似地保留和稳定在细胞内。共表达UL16显著降低细胞表面MICB、ULBP1和ULBP2的水平，并降低对自然杀伤细胞介导的细胞毒的敏感性。结构域交换实验表明，UL16的跨膜和胞质结构域对于UL16的胞内保留是重要的，而UL16的胞外结构域参与了NKG2D配体的下调。UL16对NKG2D配体的细胞内隔离代表了一种新的HCMV免疫逃避机制，为已有文献证明的针对经典MHC分子抗原提呈的病毒策略增添了一种新的机制。
The activating receptor, NKG2D, is expressed on a variety of immune effector cells and recognizes divergent families of major histocompatibility complex (MHC) class I–related ligands, including the MIC and ULBP proteins. Infection, stress, or transformation can induce NKG2D ligand expression, resulting in effector cell activation and killing of the ligand-expressing target cell. The human cytomegalovirus (HCMV) membrane glycoprotein, UL16, binds to three of the five known ligands for human NKG2D. UL16 is retained in the endoplasmic reticulum and cis-Golgi apparatus of cells and causes MICB to be similarly retained and stabilized within cells. Coexpression of UL16 markedly reduces cell surface levels of MICB, ULBP1, and ULBP2, and decreases susceptibility to natural killer cell–mediated cytotoxicity. Domain swapping experiments demonstrate that the transmembrane and cytoplasmic domains of UL16 are important for intracellular retention of UL16, whereas the ectodomain of UL16 participates in down-regulation of NKG2D ligands. The intracellular sequestration of NKG2D ligands by UL16 represents a novel HCMV immune evasion mechanism to add to the well-documented viral strategies directed against antigen presentation by classical MHC molecules.
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DOI：
10.1083/jcb.145.5.923
发表时间：
1999-05-31
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bonifacino JS;Dell'Angelica EC
通讯作者：
Dell'Angelica EC
影响因子：
5.4
作者：
Huber, MT;Tomazin, R;Johnson, DC
通讯作者：
Johnson, DC
影响因子：
56.9
作者：
Bauer, S;Groh, V;Spies, T
通讯作者：
Spies, T
DOI：
10.1073/pnas.91.14.6259
发表时间：
1994-07-05
影响因子：
11.1
作者：
BAHRAM, S;BRESNAHAN, M;SPIES, T
通讯作者：
SPIES, T
DOI：
10.1073/pnas.93.22.12445
发表时间：
1996-10-29
影响因子：
11.1
作者：
Groh, V;Bahram, S;Spies, T
通讯作者：
Spies, T