A nanoscale reorganization of the IL-15 receptor is triggered by NKG2D in a ligand-dependent manner.
A nanoscale reorganization of the IL-15 receptor is triggered by NKG2D in a ligand-dependent manner.
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DOI：
10.1126/scisignal.aal3606
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发表时间：
2018-04-10
影响因子：
7.3
通讯作者：
Davis DM
中科院分区：
文献类型：
--
作者：
Bálint Š;Lopes FB;Davis DM
自然杀伤组2D（NKG 2D）是自然杀伤（NK）细胞和T细胞亚群上的活化受体，识别存在于感染或转化细胞上的应激诱导蛋白，包括云母和ULBP 2。每个NKG 2D配体（NKG 2DL）是否具有不同的生物学作用尚不清楚。在这里，使用超分辨率显微镜，我们发现NKG 2D在原代人NK细胞表面组成性地排列在纳米簇中。NKG 2D的纳米簇在与云母连接后变小，但在被ULBP 2激活后变大。此外，ULBP 2诱导白细胞介素-2（IL-2）和IL-15（IL-2/IL-15 R β）的细胞因子受体亚基纳米簇重组，使得这些细胞因子受体亚基与NKG 2D纳米簇合并。在功能上，ULBP 2激活的NK细胞的应答通过ULBP 2结合的NKG 2D和IL-15连接的IL-15 R（通过IL-15 R α包被的表面反式呈递）之间的相互作用而增强。这些数据表明，NKG 2DL在激活NKG 2D的能力方面并不等同，并在配体诱导的细胞表面纳米级组织变化如何影响免疫反应方面建立了一个先前未知的范例。
Natural killer group 2D (NKG2D), an activating receptor on natural killer (NK) cells and a subset of T cells, recognizes stress-inducible proteins, including MICA and ULBP2, which are present on infected or transformed cells. Whether each NKG2D ligand (NKG2DL) has a distinct biological role is not clear. Here, using superresolution microscopy, we found that NKG2D is constitutively arranged in nanoclusters at the surface of primary human NK cells. Nanoclusters of NKG2D became smaller upon ligation with MICA but became larger upon activation by ULBP2. Additionally, ULBP2 induced the reorganization of nanoclusters of the cytokine receptor subunit for both interleukin-2 (IL-2) and IL-15 (IL-2/IL-15Rβ) such that these cytokine receptor subunits coalesced with nanoclusters of NKG2D. Functionally, the response of NK cells activated by ULBP2 was augmented by an interaction between ULBP2-bound NKG2D and IL-15R ligated by IL-15 (trans-presented by IL-15Rα–coated surfaces). These data suggest that NKG2DLs are not equivalent in their capacity to activate NKG2D and establish a previously unknown paradigm in how ligand-induced changes to the nanoscale organization of the cell surface can affect immune responses.
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