Analysis of signaling molecules for NK cell receptors

NK 细胞受体信号分子分析

• 批准号: 09670328
• 负责人: ARASE Hisashi
• 金额: $ 2.3万
• 依托单位: Chiba University Graduate School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670328/
• 关键词: NKR-P1; CD161; CD16; FcRgamma chain; ADCC; NK cell; IFN-gamma; CD3zetachain

NKR-P1 molecule is thought to be one of activating receptor for NK cells and suggested to play an important role in cytotoxicity and IFN-gamma production by NK cells. Therefore, it is important to clarify the signaling mechanism of NKR-P1 molecule. In this study, in order to clarify the signaling pathway for NKR-P1 molecule, we analyzed association molecule for NKR-P1 and found that FcRgamma chain is associated with NKR-P1. Furthermore, analysis using FcRgamma-deficient mice revealed that FcRgamma is essential for signal transduction of NKR-P1.On the other hand, NK cells are known to express CD3zetachain, a signal transducing molecule for TCR.However, the role of GD3zetaon NK cells has remained unclear, In order to analyze the function of CD3zeta expressed on NK cells, we purified NK cells from CD3zeta deficient mice and analyzed expression of various surface molecules. Then, we found that expression of FcgammaRIII is significantly high on NK cells from CD3zeta-deficient mice compared with that from normal mice. Furthermore, NK cells from CD3zeta-deficient mice produced a large amount of IFN-gammacompared with those from normal mice upon stimulation with FcgammaRIII crosslinking. These findings showed that CD3zetachain has an important role for the regulation of expression of FcgammaRIII on NK cells.

NKR-P1分子被认为是NK细胞的激活受体之一，并建议在NK细胞中发挥重要作用在细胞毒性和IFN-GAMMA产生中。因此，重要的是阐明NKR-P1分子的信号传导机制。在这项研究中，为了阐明NKR-P1分子的信号传导途径，我们分析了NKR-P1的关联分子，发现FCRGAMMA链与NKR-P1有关。此外，使用FCRGAMMA缺陷小鼠进行分析表明，FCRGAMMA对于NKR-P1的信号转导至关重要来自CD3ZETA缺乏小鼠的NK细胞并分析了各种表面分子的表达。然后，我们发现与正常小鼠相比，CD3ZETA缺陷小鼠的NK细胞的Fcgammariii表达显着高。此外，来自CD3ZETA缺陷的小鼠的NK细胞在用FCGAMMARIII交联后，产生了大量与正常小鼠的IFN-IFN-Gammacompary。这些发现表明，CD3Zetachain在调节NK细胞上表达表达具有重要作用。

项目成果

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Yamazaki, T.：“通过 TCR 转基因 CD3zeta 缺陷小鼠中 TCR 信号水平的降低，自身反应性 T 细胞从阴性选择转变为阳性选择。”

Watanabe, N.: "Th1 and Th2 subsets equally undergo Fas-dependent and independent activation-induced cell death." Eur.J.Immunol.27. 1858-1864 (1997)

Watanabe, N.：“Th1 和 Th2 亚群同样经历 Fas 依赖性和独立激活诱导的细胞死亡。”

Saijyo,K.et al.: "Crucial role of Jak3 in negative selection of self-reactive T cells." J.Exp.Med.185. 351-356 (1997)

Saijyo,K.et al.：“Jak3 在自身反应性 T 细胞阴性选择中的关键作用。”

Onoe,K.et al.: "Influence of graft versus host reaction on the T cell reperioire differentiating from bone marrow precursors following allogeneic bone marrow transplantation." Transpl.Immunol.5. 75-82 (1997)

Onoe, K. 等人：“移植物抗宿主反应对同种异体骨髓移植后与骨髓前体细胞分化的 T 细胞库的影响。”

Arase, N.et al.: "Association with FcRγ is essential for activation signal through NKR-P1(CD161) NK cells and NK1.1_+ cells." J.Exp.Med.186. 1957-1963 (1997)

Arase, N.等人：“与 FcRγ 的关联对于通过 NKR-P1(CD161) NK 细胞和 NK1.1_+ 细胞的激活信号至关重要。”J.Exp.Med.1957-1963 (1997)。