Association with FcRγ is essential for activation signal through NKR-P1 (CD161) in natural killer (NK) cells and NK1.1+ T cells
Association with FcRγ is essential for activation signal through NKR-P1 (CD161) in natural killer (NK) cells and NK1.1+ T cells
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DOI：
10.1084/jem.186.12.1957
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发表时间：
1997-12-15
影响因子：
15.3
通讯作者：
Saito, T
中科院分区：
文献类型：
--
作者：
Arase, N;Arase, H;Saito, T
自然杀伤（NK）细胞对多种肿瘤细胞和病毒感染的细胞表现出细胞毒性，而无需预先致敏，并代表参与主要宿主防御的独特淋巴细胞。NKR-P1被认为是介导活化信号的NK受体之一，因为NKR-P1的交联活化NK细胞以显示细胞毒性和IFN-γ产生。然而，通过NKR-P1激活NK细胞的分子机制还没有很好地阐明。在这项研究中，我们分析了NK细胞上与NKR-P1相关的细胞表面复合物，发现NKR-P1与FcR γ链相关，FcR γ链是IgG和IgE Fc受体的重要组成部分。FcR γ和NKR-P1之间的结合不依赖于Fc受体复合物。此外，来自FcR γ缺陷型小鼠的NK细胞在NKR-P1交联后未显示细胞毒性或IFN-γ产生。类似地，来自FcR γ缺陷小鼠的NK1.1（+）T细胞在NKR-P1交联后不产生IFN-γ。这些发现表明，FcR γ链通过NKR-P1分子在NK细胞活化中起重要作用。
Natural killer (NK) cells exhibit cytotoxicity against variety of tumor cells and virus-infected cells without prior sensitization and represent unique lymphocytes involved in primary host defense. NKR-P1 is thought to be one of NK receptors mediating activation signals because cross-linking of NKR-P1 activates NK cells to exhibit cytotoxicity and IFN-gamma production. However, molecular-mechanism of NK cell activation via NKR-P1 is not well elucidated. In this study, we analyzed the cell surface complex associated with NKR-P1 on NK cells and found that NKR-P1 associates with the FcR gamma chain which is an essential component of Fc receptors for IgG and IgE. The association between FcR gamma and NKR-P1 is independent of Fc receptor complexes. Furthermore, NK cells from FcR gamma-deficient mice did not show cytotoxicity or IFN-gamma production upon NKR-P1 cross-linking. Similarly, NK1.1(+) T cells from FcR gamma-deficient mice did not produce IFN-gamma upon NKR-P1 crosslinking. These findings demonstrate that the FcR gamma chain plays an important role in activation of NK cells via the NKR-P1 molecule.