Recruitment of activation receptors at inhibitory NK cell immune synapses.
Recruitment of activation receptors at inhibitory NK cell immune synapses.
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DOI：
10.1371/journal.pone.0003278
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发表时间：
2008-09-26
期刊：
影响因子：
3.7
通讯作者：
Long EO
中科院分区：
文献类型：
--
作者：
Schleinitz N;March ME;Long EO
自然杀伤(NK)细胞激活受体通过依赖肌动蛋白的过程在细胞毒性免疫突触积聚，在那里它们提供触发NK细胞效应器功能的协同信号。相反，NK细胞抑制性受体，包括MHC-I类特异性杀伤细胞Ig样受体(KIR)家族的成员，聚集在抑制性免疫突触，阻断肌动蛋白动力学，并阻止激活受体的肌动蛋白依赖的磷酸化。因此，人们可以预测，当抑制受体被激活时，依赖肌动蛋白的激活受体的积累将受到抑制。通过与表达NK细胞受体生理配体的靶细胞接触的原代人类NK细胞的共聚焦成像，我们在这里表明这一预测是错误的。靶细胞包括人类细胞系和表达NK细胞激活受体配体和MHC-I类抑制性KIR配体的转基因果蝇昆虫细胞。NK细胞活化受体CD2和2B4与KIR共定位于抑制性免疫突触。事实上，KIR促进了CD2和2B4的聚集，因为CD2和2B4在抑制性突触积累得更有效。相反，KIR和激活受体在抑制性突触的积累与整合素LFA-1密度的降低有关。这些结果表明，抑制性KIR并不是通过阻止CD2和2B4在NK细胞免疫突触上的聚集来阻止它们的信号传递，而是通过阻断它们在抑制性突触内的信号传递能力来阻止它们。
Natural killer (NK) cell activation receptors accumulate by an actin-dependent process at cytotoxic immune synapses where they provide synergistic signals that trigger NK cell effector functions. In contrast, NK cell inhibitory receptors, including members of the MHC class I-specific killer cell Ig-like receptor (KIR) family, accumulate at inhibitory immune synapses, block actin dynamics, and prevent actin-dependent phosphorylation of activation receptors. Therefore, one would predict inhibition of actin-dependent accumulation of activation receptors when inhibitory receptors are engaged. By confocal imaging of primary human NK cells in contact with target cells expressing physiological ligands of NK cell receptors, we show here that this prediction is incorrect. Target cells included a human cell line and transfected Drosophila insect cells that expressed ligands of NK cell activation receptors in combination with an MHC class I ligand of inhibitory KIR. The two NK cell activation receptors CD2 and 2B4 accumulated and co-localized with KIR at inhibitory immune synapses. In fact, KIR promoted CD2 and 2B4 clustering, as CD2 and 2B4 accumulated more efficiently at inhibitory synapses. In contrast, accumulation of KIR and of activation receptors at inhibitory synapses correlated with reduced density of the integrin LFA-1. These results imply that inhibitory KIR does not prevent CD2 and 2B4 signaling by blocking their accumulation at NK cell immune synapses, but by blocking their ability to signal within inhibitory synapses.
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影响因子：
4.4
作者：
Almeida, Catarina R.;Davis, Daniel M.
通讯作者：
Davis, Daniel M.
DOI：
10.1073/pnas.97.18.10150
发表时间：
2000-08-29
影响因子：
11.1
作者：
Wülfing, C;Bauch, A;Davis, MM
通讯作者：
Davis, MM
DOI：
10.1084/jem.185.8.1523
发表时间：
1997-04-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Rajagopalan S;Long EO
通讯作者：
Long EO
影响因子：
4.4
作者：
Roda-Navarro, P;Mittelbrunn, M;Fernández-Ruiz, E
通讯作者：
Fernández-Ruiz, E
影响因子：
4.4
作者：
Faure, M;Barber, DF;Long, EO
通讯作者：
Long, EO