A novel ligand for the NKG2D receptor activates NK cells and macrophages and induces tumor immunity
A novel ligand for the NKG2D receptor activates NK cells and macrophages and induces tumor immunity
复制标题
DOI：
10.1002/immu.200310012
复制
发表时间：
2003-02-01
影响因子：
5.4
通讯作者：
Raulet, DH
中科院分区：
文献类型：
--
作者：
Diefenbach, A;Hsia, JK;Raulet, DH
NK细胞参与对抗病毒、微生物感染和肿瘤的免疫反应。与B细胞和T细胞相比，NK细胞采用各种免疫识别模式。NK细胞采用的一种重要的免疫识别模式是“诱导自我识别”，例如NKG2D受体-配体系统。NKG2D免疫受体由NK细胞和活化的CD8(+) T细胞和巨噬细胞表达，识别与MHC I类分子（即小鼠的H60和Rae1蛋白，以及人类的MHC I类链相关蛋白和ul -16结合蛋白）有远亲关系的几种细胞表面配体之一。这些配体在大多数正常细胞中不大量表达，但在暴露于各种形式的细胞损伤的细胞中表达上调。在这里，我们报道了NKG2D的另一个配体的克隆；这种配体的转录本广泛存在于各种组织和各种肿瘤细胞中。NKG2D与新型配体交联可有效激活NK细胞和巨噬细胞。异位表达该分子的肿瘤细胞被幼稚小鼠有效排斥，并诱导对亲代配体阴性肿瘤细胞的强保护性免疫。
NK cells are involved in the immune response against viral and microbial infections and tumors. In contrast to B and T cells, NK cells employ various modes of immune recognition. An important mode of immune recognition employed by NK cells is "induced self recognition" exemplified by the NKG2D receptor-ligand system. The NKG2D immunoreceptor, expressed by NK cells, and by activated CD8(+) T cells and macrophages, recognizes one of several cell surface ligands that are distantly related to MHC class I molecules (i.e. H60 and Rae1 proteins in mice, and MHC class I chain-related proteins and UL-16-binding proteins in humans). These ligands are not expressed abundantly by most normal cells but are upregulated on cells exposed to various forms of cellular insults. Here we report the cloning of another ligand for NKG2D; transcripts of this ligand are found in a wide variety of tissues and in various tumor cells. Cross-linking of NKG2D with the novel ligand potently activated NK cells and macrophages. Tumor cells ectopically expressing the molecule were efficiently rejected by naive mice, and induced strong protective immunity to the parental, ligand-negative tumor cells.