Interaction of natural killer cells with MHC class II: Reversal of HLA-DR1-mediated protection of K562 transfectant from natural killer cell-mediated cytolysis by brefeldin-A
Interaction of natural killer cells with MHC class II: Reversal of HLA-DR1-mediated protection of K562 transfectant from natural killer cell-mediated cytolysis by brefeldin-A
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DOI：
10.1046/j.1365-2567.1996.483556.x
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发表时间：
1996-03-01
期刊：
影响因子：
6.4
通讯作者：
Barrett, AJ
中科院分区：
文献类型：
--
作者：
Jiang, YZ;Couriel, D;Barrett, AJ
肿瘤细胞表面的主要组织相容性复合体（MHC）I类抗原已被证明可以调节靶向对自然杀伤（NK）细胞介导的溶解的敏感性，尽管不是所有的系统研究。MHC II类抗原的表达也可能影响NK细胞的功能，但MHC II类抗原调节NK细胞活性的机制尚未得到充分研究。在这项研究中，我们诱导HLA-DR 1基因转染到经典的NK敏感的K562细胞系的表达，研究NK细胞与MHC II类分子的相互作用和布雷菲德菌素-A（BFA），内源性抗原加工通路阻断剂，对NK细胞-靶细胞相互作用的影响。我们证明了细胞表面HLA-DR 1的表达降低了K562细胞对外周血单核细胞和NK细胞系的NK溶解的敏感性。该作用在延长的（8小时）细胞毒性测定中是可证实的，并且通过用抗HLA-DR抗体预处理靶细胞而被阻断。用BFA处理K562 DR转染子可消除K562转染子对NK介导的细胞溶解的抗性。这些发现表明，HLA II类分子调节NK细胞的功能和目标识别，并表明，通过MHC分子的内源性肽是负责调节NK细胞溶解。
Major histocompatibility complex (MHC) class I antigens on tumour cell surfaces have been shown to modulate target susceptibility to natural killer (NK) cell-mediated lysis in some, although not all, systems investigated. MHC class II expression may also affect NK cell function, but the mechanism by which MHC class II antigen regulates NK cell activity has not been fully examined. In this study we induced HLA-DR1 expression by gene transfection into the classic NK-sensitive K562 cell line to study the interaction of NK cells with MHC class II molecules and the effect of brefeldin-A (BFA), an endogenous antigen-processing pathway blocker, on NK-target cell interaction. We demonstrated that the expression of HLA-DR1 on the cell surface reduced K562 cell susceptibility to NK lysis by peripheral blood monuclear cells and a NK cell line. The effect was demonstrable in prolonged (8 hr) cytotoxicity assays and was blocked by pretreatment of target cells with anti-HLA-DR antibody. Treatment of K562 DR transfectant with BFA abrogated the resistance of K562 transfectant to NK-mediated cytolysis. These findings indicate that HLA class II molecules regulate NK cell function and target recognition, and suggest that endogenous peptides presented through MHC molecules are responsible for regulating NK cytolysis.