The human natural killer cell immune synapse
The human natural killer cell immune synapse
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DOI：
10.1073/pnas.96.26.15062
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发表时间：
1999-12-21
影响因子：
11.1
通讯作者：
Strominger, JL
中科院分区：
文献类型：
--
作者：
Davis, DM;Chiu, I;Strominger, JL
自然杀伤细胞（NK）表面的抑制性杀伤细胞样受体（KIR）诱导HLA-C在靶细胞接触表面聚集。通过这种方式，人类NK细胞在检测靶细胞时形成了抑制性免疫突触。在靶细胞/NK细胞突触，HLA-C/KIR分布在细胞间粘附分子-1/淋巴细胞功能相关抗原-1的中心斑块周围，与成熟的小鼠T细胞激活突触相反。这种蛋白质组织至少稳定20分钟。细胞可以同时支持多个突触，当NK细胞爬过靶细胞时，HLA-C簇移动，聚类需要二价金属阳离子，这解释了金属螯合剂如何抑制KIR功能。然而，令人惊讶的是，抑制性突触的形成不受ATP耗尽和细胞骨架抑制剂秋水秋碱和细胞松弛素B和D的影响。显然，质膜内的超分子组织对NK细胞免疫监视至关重要。
Inhibitory killer lg-like receptors (KIR) at the surface of natural killer (NK) cells induced clustering of HLA-C at the contacting surface of target cells. In this manner, inhibitory immune synapses were formed as human NK cells surveyed target cells. At target/NK cell synapses, HLA-C/KIR distributed into rings around central patches of intercellular adhesion molecule-1/lymphocyte function-associated antigen-1, the opposite orientation to mature murine T cell-activating synapses. This organization of protein was stable for at least 20 min. Cells could support multiple synapses simultaneously, and clusters of HLA-C moved as NK cells crawled over target cells, Clustering required a divalent metal cation, explaining how metal chelators inhibit KIR function, Surprisingly, however, formation of inhibitory synapses was unaffected by ATP depletion and the cytoskeletal inhibitors, colchicine and cytochalsins B and D, Clearly, supramolecular organization within plasma membranes is critical for NK cell immunosurveillance.