Arnon T I, Lev M, Katz G, Chernobrov Y, Porgador A, Mandelboim O
The Lautenberg Center for General and Tumor Immunology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Eur J Immunol. 2001 Sep;31(9):2680-9. doi: 10.1002/1521-4141(200109)31:9<2680::aid-immu2680>3.0.co;2-a.
Natural killer (NK) cells destroy virus-infected and tumor cells without prior antigen stimulation. The NK cell cytotoxicity is regulated in large part by the expression of NK cell receptors that are able to bind major histocompatibility complex (MHC) class I glycoproteins. NK cells also express lysis triggering receptors specific for non-MHC ligands, including NKp30, NKp44, NKp46 and CD16. However, the nature of their ligands, recognized on target cells, is undefined. We have recently shown that the NKp46 protein, but not the CD16 protein, recognizes the hemagglutinin (HA) of influenza virus (IV) and the hemagglutinin-neuraminidase (HN) of Sendai virus (SV), and that the recognition of HA from IV requires the sialylation of NKp46 oligosaccharides. We have also demonstrated that binding of NKp46 to HA of IV is required for lysis of cells expressing the corresponding glycoproteins by a substantial subset of NK clones. Here we show that NKp44, but not NKp30, can also recognize the HA of both IV and SV and that the recognition of IV HA requires the sialylation of the NKp44 receptor in a similar way to that of NKp46. SV infection of 721.221 cells expressing MHC class I proteinsresulted in the abrogation of the inhibition by NK clones expressing high levels of NKp44. In addition, the binding of NKp44 to HA improves the ability of some NK clones to lyse IV infected cells.
自然杀伤（NK）细胞无需预先抗原刺激就能破坏病毒感染细胞和肿瘤细胞。NK细胞的细胞毒性在很大程度上受能够结合主要组织相容性复合体（MHC）I类糖蛋白的NK细胞受体表达的调节。NK细胞还表达对非MHC配体特异的裂解触发受体，包括NKp30、NKp44、NKp46和CD16。然而，它们在靶细胞上识别的配体的性质尚不清楚。我们最近发现，NKp46蛋白而非CD16蛋白能识别流感病毒（IV）的血凝素（HA）和仙台病毒（SV）的血凝素神经氨酸酶（HN），并且IV型HA的识别需要NKp46寡糖的唾液酸化。我们还证明，NKp46与IV型HA的结合是相当一部分NK克隆裂解表达相应糖蛋白的细胞所必需的。在此我们表明，NKp44而非NKp30也能识别IV型和SV型的HA，并且IV型HA的识别以与NKp46类似的方式需要NKp44受体的唾液酸化。表达MHC I类蛋白的721.221细胞感染SV导致表达高水平NKp44的NK克隆的抑制作用被消除。此外，NKp44与HA的结合提高了一些NK克隆裂解IV感染细胞的能力。
