Inhibitory receptors alter natural killer cell interactions with target cells yet allow simultaneous killing of susceptible targets.

Inhibitory receptors alter natural killer cell interactions with target cells yet allow simultaneous killing of susceptible targets.
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抑制性受体改变自然杀伤细胞与靶细胞的相互作用,但允许同时杀死敏感靶标。

DOI:
10.1084/jem.190.7.1005
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发表时间:
1999-10-04
影响因子:
15.3
通讯作者:
Sentman, C L
Sentman, C L
中科院分区:
医学1区
文献类型:
--
作者:
Eriksson, M;Leitz, G;Fallman, E;Axner, O;Ryan, J C;Nakamura, M C;Sentman, C L

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在自然杀伤(NK)细胞上表达的抑制性受体通过在各种靶细胞上结合相应的主要组织相容性复合体(MHC) I类分子来消除阳性信号。通过使用允许时间和空间控制的光学镊子系统直接微操纵效应-靶细胞相遇,我们证明了Ly49-MHC I类相互作用在与靶细胞结合时阻止NK细胞的特征细胞反应。此外,使用该系统,我们直接证明了已经与抗性靶细胞结合的NK细胞可以同时结合并杀死易感靶细胞。因此,尽管ly49介导的抑制信号可以阻止许多类型的效应反应,但它们并不全局地抑制细胞功能,而是抑制信号在空间上被限制在耐药靶点。
Inhibitory receptors expressed on natural killer (NK) cells abrogate positive signals upon binding corresponding major histocompatibility complex (MHC) class I molecules on various target cells. By directly micromanipulating the effector–target cell encounter using an optical tweezers system which allowed temporal and spatial control, we demonstrate that Ly49–MHC class I interactions prevent characteristic cellular responses in NK cells upon binding to target cells. Furthermore, using this system, we directly demonstrate that an NK cell already bound to a resistant target cell may simultaneously bind and kill a susceptible target cell. Thus, although Ly49-mediated inhibitory signals can prevent many types of effector responses, they do not globally inhibit cellular function, but rather the inhibitory signal is spatially restricted towards resistant targets.