Mandelboim O, Lieberman N, Lev M, Paul L, Arnon T I, Bushkin Y, Davis D M, Strominger J L, Yewdell J W, Porgador A
The Lautenberg Center for General and Tumor Immunology, The Hebrew University-Hadassha Medical School, Jerusalem, Israel.
Nature. 2001 Feb 22;409(6823):1055-60. doi: 10.1038/35059110.
Natural killer (NK) cells destroy virus-infected and tumour cells, apparently without the need for previous antigen stimulation. In part, target cells are recognized by their diminished expression of major histocompatibility complex (MHC) class I molecules, which normally interact with inhibitory receptors on the NK cell surface. NK cells also express triggering receptors that are specific for non-MHC ligands; but the nature of the ligands recognized on target cells is undefined. NKp46 is thought to be the main activating receptor for human NK cells. Here we show that a soluble NKp46-immunoglobulin fusion protein binds to both the haemagglutinin of influenza virus and the haemagglutinin-neuraminidase of parainfluenza virus. In a substantial subset of NK cells, recognition by NKp46 is required to lyse cells expressing the corresponding viral glycoproteins. The binding requires the sialylation of NKp46 oligosaccharides, which is consistent with the known sialic binding capacity of the viral glycoproteins. These findings indicate how NKp46-expressing NK cells may recognize target cells infected by influenza or parainfluenza without the decreased expression of target-cell MHC class I protein.
自然杀伤（NK）细胞可破坏病毒感染细胞和肿瘤细胞，显然无需预先的抗原刺激。部分原因是，靶细胞通过主要组织相容性复合体（MHC）I类分子表达减少而被识别，MHC I类分子通常与NK细胞表面的抑制性受体相互作用。NK细胞还表达对非MHC配体具有特异性的触发受体；但靶细胞上被识别的配体的性质尚不清楚。NKp46被认为是人类NK细胞的主要激活受体。我们在此表明，可溶性NKp46-免疫球蛋白融合蛋白可与流感病毒的血凝素以及副流感病毒的血凝素-神经氨酸酶结合。在相当一部分NK细胞中，NKp46识别是裂解表达相应病毒糖蛋白的细胞所必需的。这种结合需要NKp46寡糖的唾液酸化，这与病毒糖蛋白已知的唾液酸结合能力一致。这些发现表明表达NKp46的NK细胞如何识别感染流感或副流感的靶细胞，而靶细胞MHC I类蛋白的表达并未降低。
