一种新的NK细胞细胞毒活化型膜受体作用的分子机制

明确PTA1分子在新鲜分离人NK细胞、NK细胞克隆和NK细胞系分布、活化NK细胞毒功能以及细胞因子调节PTA1表达，探讨PTA1与其它NK细胞活化型或抑制型受体介导细胞毒的协同或拮抗规律，搞清PTA1刺激NK细胞活化时细胞因子的产生、PTA1胞浆区磷酸化、信号分子变化以及PKC所起的作用，从而阐明PTA1这一新的活化型膜分子刺激NK细胞杀伤的分子机制。

Natural killer cells are the lymphocytes involved in innate immunity . PTA1 cDNAs of gibbon and monkey were cloned in our lab in 1997 and human PTA1 was designated as CD226 at the 7th HLDA in 2000.In this study,the regulation of CD226 expression ,as well as other activation receptors and inhibition receptors on NK cells were detected by double-immunofluorescent staining and FCM analysis.The results showed that CD226 was expressed on activated NK cells, NK cell clone ,and NK92 and NKL cell lines,wheares only low level of CD226 expression on resting NK cell was observed.In mixed lymphocyte culture(MLC),IL-15 was more effective than IL-2 on upregulating the expression of CD56 and CD226.Interestingly,the phenotype of NK cells in MLC was largely shifted from CD56dimCD226-/low to CD56brightCD226+/high in the presence of IL-15.Moreover,the expression of CD226 on NK cells could be increased by superantigen SEA or SEB.In addition,the cytotoxicity of NK cells,NK cell clone and NK92 cell line were investigated by redirected cytotoxicity assay (RCA).The results showed that CD226 mAb could upregulate the cytotoxicity of NK cells,NK cell clone and NK92. Meanwhile the levels of IFN-γand GM-CSF in the superntant from RCA were increased by the addition of CD226 mAb .Furthermore,IL-15 was more effective than IL-2 on enhancing the cytotoxicity of both resting NK cells and activated NK cells.In conclusion,CD226 is a novel membrane activation receptor on NK cells.