抗MHC I类单抗对NK细胞杀伤能力的影响

张　彩　田志刚　张建华　许晓群　孙

　　中国图书分类号　R392.1
　　摘　要　目的：探讨NK细胞杀伤与靶细胞表面MHC I类分子的关系。方法：用HLA-ABC单抗培养上清或腹水封闭靶细胞K562表面的HLA-ABC分子后，分别观察了外周血新鲜NK细胞、纯化NK细胞、LAK细胞和CD3AK细胞对K562细胞杀伤能力的变化。结果：外周血新鲜NK细胞和纯化NK细胞对K562的杀伤率明显提高，CD3AK细胞的杀伤力明显降低，LAK细胞的杀伤无明显变化。结论：NK细胞通过其表面受体识别靶细胞上的MHC I类分子而传递杀伤抑制性信号，抗HLA-ABC单抗封闭了靶细胞上的HLA-ABC等位基因而阻止了阴性信号的传导。
　　关键词　NK细胞　MHC I类分子　细胞毒活性

The effect of anti-MHC class I monoclonal antibody on NK-mediated cytolytic activity

ZHAHG Cai,TIAN Zhi-Gang,ZHANG Jian-Hua et al.
Shandong Cancer Biotherapy Center,Shandong Academy of Medical Sciences,Jinan 250062

　　Abstract Objective:To study the relation of cytolytic activity of NK cells and MHC class I molecules on target cells.Metheds:The changes of cytolytic activity of fresh NK cells seperated from peripheral blood,purified NK cells,LAK cells and CD3AK cells were observed when target cells were cultured with anti-HLA-ABC monoclonal antibody for 30 minutes.Results:The cytolytic activity of fresh NK cells and purified NK cells from LAK cells was highly increased,but that of CD3AK cells was lowered.The cytotxicity of LAK cells was not affected.Conclution:NK cell can recognize the MHC class I molecules on target cells and then inhibit its cytolytic activity by transmitting kill-inhibitory signals.The anti-HLA-ABC monoclonal antibody had prevented the delivering of negative signals by blocking the MHC class I molecules on target cells.
　　Key words NK cells MHC class I molecules Cytolytic actioity

　　NK细胞是表型和功能上独特的淋巴细胞亚群，是机体抵抗病毒感染和肿瘤生长的第一道防线，不需预先刺激即可介导广谱的杀瘤效应。由于NK细胞对不表达MHC分子的肿瘤细胞同样具有较高的杀伤能力，多年来人们通常认为NK细胞介导的细胞毒效应是MHC非限制性的。近年来，随着对NK细胞研究的深入，人们发现NK细胞杀伤的敏感性与靶细胞上MHC I类分子的表达密切相关，对不表达MHC I类分子或表达量较低的靶细胞杀伤力强，对表达MHC I类分子高的靶细胞杀伤力较弱或不杀伤。这方面的研究已逐步成为肿瘤免疫学研究的热点内容之一［1～4］。本文初步观察了MHC I类单抗对NK细胞杀伤能力的影响，现报告如下。

1　材料与方法
1.1　K562细胞为本室常规传代培养　鼠抗人HLA-ABC、HLA-DR单抗杂交瘤细胞(ATCC引入)培养上清及腹水、新鲜兔血清均为本室自制。
1.2　LAK、CD3AK细胞的诱导　常规分离正常人外周血淋巴细胞，调至2×106～3×106ml-1，用rhI

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