Two novel NKG2D ligands of the mouse H60 family with differential expression patterns and binding affinities to NKG2D
Two novel NKG2D ligands of the mouse H60 family with differential expression patterns and binding affinities to NKG2D
复制标题
DOI：
10.4049/jimmunol.180.3.1678
复制
发表时间：
2008-02-01
影响因子：
4.4
通讯作者：
Kasahara, Masanori
中科院分区：
文献类型：
--
作者：
Takada, Akio;Yoshida, Shigeru;Kasahara, Masanori
H60最初被描述为显性次要组织相容性Ag，是一种MHC I类分子，作为NKG 2D受体的配体。在本研究中，我们确定了两个新的小鼠10号染色体编码的NKG 2D配体结构类似于H60。这些配体，我们命名为H60 b和H60 c，编码具有两个胞外结构域的MHC I类分子。H60 b具有跨膜区，而H60 c是GPI锚定蛋白。重组可溶性H60 b和H60 c蛋白以细胞-细胞识别受体的典型亲和力与NKG 2D结合（H60 b的Kd = 310 nM，H60 c的Kd = 8.7 μ M）。此外，H60 b或H60 c的表达使Ba/F3细胞易于被NK细胞裂解，从而确立H60 b和H60 c作为NKG 2D的功能性配体。H60 b和H60 c转录本在健康成年小鼠的组织中仅以低水平检测到。而H60 b转录本在各种组织中检测到，H60 c转录本主要在皮肤中检测到。感染小鼠胚胎成纤维细胞与鼠巨细胞病毒诱导表达H60 b，但不是H60 c或以前已知的H60基因，表明转录激活的三种类型的H60基因的差异调节。本研究为目前的NKG 2D配体列表增加了两个新成员。
H60, originally described as a dominant minor histocompatibility Ag, is an MHC class I-like molecule that serves as a ligand for the NKG2D receptor. In the present study, we identified two novel mouse chromosome 10-encoded NKG2D ligands structurally resembling H60. These ligands, which we named H60b and H60c, encode MHC class I-like molecules with two extracellular domains. Whereas H60b has a transmembrane region, H60c is a GPI-anchored protein. Recombinant soluble H60b and H60c proteins bound to NKG2D with affinities typical of cell-cell recognition receptors (K-d = 310 nM for H60b and K-d = 8.7 mu M for H60c). Furthermore, expression of H60b or H60c rendered Ba/F3 cells susceptible to lysis by NK cells, thereby establishing H60b and H60c as functional ligands for NKG2D. H60b and H60c transcripts were detected only at low levels in tissues of healthy adult mice. Whereas H60b transcripts were detectable in various tissues, H60c transcripts were detected mainly in the skin. Infection of mouse embryonic fibroblasts with murine cytomegalovirus induced expression of H60b, but not H60c or the previously known H60 gene, indicating that transcriptional activation of the three types of H60 genes is differentially regulated. The present study adds two new members to the current list of NKG2D ligands.