Pende D, Cantoni C, Rivera P, Vitale M, Castriconi R, Marcenaro S, Nanni M, Biassoni R, Bottino C, Moretta A, Moretta L
Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Eur J Immunol. 2001 Apr;31(4):1076-86. doi: 10.1002/1521-4141(200104)31:4<1076::aid-immu1076>3.0.co;2-y.
NKG2D is a recently described activating receptor expressed by both NK cells and CTL. In this study we investigated the role of NKG2D in the natural cytolysis mediated by NK cell clones. The role of NKG2D varied depending on the type of target cells analyzed. Lysis of various tumors appeared to be exclusively natural cytotoxicity receptors (NCR) dependent. In contrast, killing of another group of target cells, including not only the epithelial cell lines HELA and IGROV-1, but also the FO-1 melanoma, the JA3 leukemia, the Daudi Burkitt lymphoma and even normal PHA-induced lymphoblasts, involved both NCR and NKG2D. Notably, NK cell clones expressing low surface densities of NCR (NCR(dull)) could lyse these tumors in an exclusively NKG2D-dependent fashion. Remarkably, not all of these targets expressed MICA/B, thus implying the existence of additional ligands recognized by NKG2D, possibly represented by GPI-linked molecules. Finally, we show that the engagement of different HLA class I-specific inhibitory receptors by either specific antibodies or the appropriate HLA class I ligand led to inhibition of NKG2D-mediated NK cell triggering.
NKG2D是一种最近被描述的由自然杀伤细胞（NK细胞）和细胞毒性T淋巴细胞（CTL）表达的激活受体。在本研究中，我们调查了NKG2D在NK细胞克隆介导的自然细胞溶解中的作用。NKG2D的作用因所分析的靶细胞类型而异。各种肿瘤的溶解似乎完全依赖于自然细胞毒性受体（NCR）。相反，另一组靶细胞的杀伤，不仅包括上皮细胞系HELA和IGROV-1，还包括FO-1黑色素瘤、JA3白血病、Daudi伯基特淋巴瘤，甚至正常的PHA诱导的淋巴母细胞，涉及NCR和NKG2D。值得注意的是，表达低表面密度NCR（NCR(dull)）的NK细胞克隆能够以完全依赖NKG2D的方式裂解这些肿瘤。值得注意的是，并非所有这些靶细胞都表达MICA/B，因此意味着存在NKG2D识别的其他配体，可能由糖基磷脂酰肌醇（GPI）连接的分子代表。最后，我们表明，通过特异性抗体或适当的HLA I类配体与不同的HLA I类特异性抑制性受体结合，会导致NKG2D介导的NK细胞触发受到抑制。
