Analysis of signaling molecules for NK cell receptors

NKR-P1分子被认为是NK细胞的活化受体之一，并被认为在NK细胞的细胞毒性和IFN-γ的产生中起重要作用。因此，阐明NKR-P1分子的信号转导机制具有重要意义。为了阐明NKR-P1分子的信号通路，本研究分析了NKR-P1的相关分子，发现FcR γ链与NKR-P1相关。此外，使用FcR γ缺陷小鼠的分析显示，FcR γ对于NKR-P1的信号传导是必需的。另一方面，已知NK细胞表达CD 3 ζ链，一种TCR的信号传导分子。然而，GD 3 ζ在NK细胞上的作用尚不清楚。为了分析NK细胞上表达的CD 3 ζ的功能，我们从CD 3 ζ缺陷小鼠中纯化NK细胞并分析各种表面分子的表达。然后，我们发现，与正常小鼠相比，来自CD 3 zeta缺陷小鼠的NK细胞上Fc γ RIII的表达显著高。此外，来自CD 3 zeta缺陷小鼠的NK细胞在用Fc γ RIII交联刺激时产生与来自正常小鼠的NK细胞相同的大量IFN-γ γ。这些发现表明，CD 3 ζ链在调节NK细胞上Fc γ RIII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.