Characterization of the recognition of tumor cells by the natural cytotoxicity receptor, NKp44
Characterization of the recognition of tumor cells by the natural cytotoxicity receptor, NKp44
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DOI：
10.1021/bi7000455
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发表时间：
2007-06-26
期刊：
影响因子：
2.9
通讯作者：
Porgador, Angel
中科院分区：
文献类型：
--
作者：
Hershkovitz, Oren;Jivov, Sergey;Porgador, Angel
NKp 44是一种天然的细胞毒性受体，在活化后由人NK细胞表达。在这项研究中，我们证明，细胞表面硫酸乙酰肝素蛋白聚糖（HSPGs），表达的靶细胞，参与识别肿瘤细胞的NKp 44。NKp 44显示硫酸乙酰肝素依赖性结合肿瘤细胞，这种结合被硫酸乙酰肝素抗体部分阻断。此外，观察到NKp 44与肝素的直接结合，并且可溶性肝素/硫酸乙酰肝素增强了用抗NKp 44单克隆抗体活化的NK 92细胞的IFN γ分泌。预测构成NKp 44推定的肝素/硫酸乙酰肝素结合位点的碱性氨基酸发生突变。肿瘤细胞对突变的NKp 44蛋白的识别显著降低，并且与它们对肝素的较低识别相关。我们先前报道了NKp 44识别流感病毒（IV）的血凝素。然而，突变的NKp 44蛋白结合IV感染细胞表达的病毒血凝素的能力不受影响。因此，我们认为硫酸乙酰肝素表位是NKp 44的配体/共配体，并参与其肿瘤识别能力。
NKp44 is a natural cytotoxicity receptor expressed by human NK cells upon activation. In this study, we demonstrate that cell surface heparan sulfate proteoglycans (HSPGs), expressed by target cells, are involved in the recognition of tumor cells by NKp44. NKp44 showed heparan sulfate-dependent binding to tumor cells; this binding was partially blocked with an antibody to heparan sulfate. In addition, direct binding of NKp44 to heparin was observed, and soluble heparin/heparan sulfate enhanced the secretion of IFN gamma by NK92 cells activated with anti-NKp44 monoclonal antibody. Basic amino acids, predicted to constitute the putative heparin/heparan sulfate binding site of NKp44, were mutated. Tumor cell recognition of the mutated NKp44 proteins was significantly reduced and correlated with their lower recognition of heparin. We previously reported that NKp44 recognizes the hemagglutinin of influenza virus (IV). Nevertheless, the ability of the mutated NKp44 proteins to bind viral hemagglutinin expressed by IV-infected cells was not affected. Thus, we suggest that heparan sulfate epitope(s) are ligands/co-ligands of NKp44 and are involved in its tumor recognition ability.