Analysis of signaling molecules for NK cell receptors

NKR-P1分子被认为是NK细胞的激活受体之一，并被认为在NK细胞的细胞毒作用和产生干扰素-γ方面发挥重要作用。因此，阐明NKR-P1分子的信号转导机制具有重要意义。在本研究中，为了阐明NKR-P1分子的信号通路，我们分析了NKR-P1的关联分子，发现FcRGamma链与NKR-P1相关。此外，对FcRGamma基因缺陷小鼠的分析表明，FcRGamma对于NKR-P1的信号转导是必不可少的。另一方面，已知NK细胞表达TCR信号转导分子CD3zetachain。然而，GD3zetaa对NK细胞的作用尚不清楚，为了分析表达在NK细胞上的CD3zeta的功能，我们从CD3zeta缺陷小鼠中分离纯化了NK细胞，并分析了各种表面分子的表达。然后，我们发现CD3zeta缺陷小鼠的NK细胞上FcGammaRIII的表达显著高于正常小鼠。此外，与正常小鼠相比，CD3zeta基因缺陷小鼠的NK细胞在FcGammaRIII交联剂刺激下产生了大量的干扰素-γ。这些结果表明，CD3zetachain在调节NK细胞表面FcGammaRIII的表达方面具有重要作用。

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.