Ly49-dependent NK cell licensing and effector inhibition involve the same interaction site on MHC ligands.
Ly49-dependent NK cell licensing and effector inhibition involve the same interaction site on MHC ligands.
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DOI：
10.4049/jimmunol.1004168
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发表时间：
2011-04-01
期刊：
影响因子：
--
通讯作者：
Yokoyama WM
中科院分区：
文献类型：
--
作者：
Choi T;Ferris ST;Matsumoto N;Poursine-Laurent J;Yokoyama WM
通过NK细胞抑制性受体与其同源自身MHC配体的相互作用，NK细胞在功能上变得有能力被其活化受体触发，这是一种称为“许可”的MHC依赖性教育过程。例如，Ly 49 A + NK细胞通过Ly 49 A抑制性受体与其MHC I类配体H2 Dd的相互作用而获得许可，而Ly 49 C + NK细胞通过H2Kb获得许可。结构研究表明，Ly 49 A抑制性受体可能与其H2 Dd配体上的两个位点相互作用，称为位点1和位点2。位点2包括H2 Dd重链和β2-微球蛋白（β 2 m）的α1/α2/α3结构域，是Ly 49 A在效应子抑制中的功能性结合位点。Ly 49 C在功能上与H2Kb中的类似位点相互作用。然而，目前尚不清楚该网站是否涉及Ly 49 A或Ly 49 C依赖的许可。在此，我们产生了表达野生型或位点2突变H2 Dd分子的转基因C57 BL/6小鼠，并研究了Ly 49 A + NK细胞是否被许可。我们还在鼠β 2 m缺陷小鼠中研究了Ly 49 A和Ly 49 C依赖性NK许可，所述鼠β 2 m缺陷小鼠是人β 2 m转基因小鼠，所述人β 2 m在β 2 m中具有物种特异性氨基酸取代。我们从这些转基因小鼠中获得的数据表明，自身MHC上的位点2对于Ly 49 A和Ly 49 C依赖性NK细胞许可至关重要。因此，NK细胞通过Ly 49许可涉及与其MHC配体的特异性相互作用，其类似于效应子抑制中涉及的那些。
NK cells become functionally competent to be triggered by their activation receptors through the interaction of NK cell inhibitory receptors with their cognate self-MHC ligands, an MHC-dependent educational process termed “licensing.” For example, Ly49A+ NK cells become licensed by the interaction of the Ly49A inhibitory receptor with its MHC class I ligand, H2Dd while Ly49C+ NK cells are licensed by H2Kb. Structural studies indicate that the Ly49A inhibitory receptor may interact with two sites, termed site 1 and site 2, on its H2Dd ligand. Site 2 encompasses the α1/α2/α3 domains of the H2Dd heavy chain and β2-microglobulin (β2m), and is the functional binding site for the Ly49A in effector inhibition. Ly49C functionally interacts with a similar site in H2Kb. However, it is currently unknown whether this same site is involved in Ly49A or Ly49C-dependent licensing. Herein, we produced transgenic C57BL/6 mice expressing wild type or site 2 mutant H2Dd molecules and studied whether or not Ly49A+ NK cells are licensed. We also investigated Ly49A and Ly49C-dependent NK licensing in murine β2m-deficient mice which are transgenic for human β2m which has species-specific amino acid substitutions in β2m. Our data from these transgenic mice indicate that site 2 on self-MHC is critical for Ly49A and Ly49C-dependent NK cell licensing. Thus, NK cell licensing through Ly49 involves specific interactions with its MHC ligand that are similar to those involved in effector inhibition.
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影响因子：
4.4
作者：
Michaëlsson, J;Achour, A;Kärre, K
通讯作者：
Kärre, K
DOI：
10.1073/pnas.93.21.11792
发表时间：
1996-10-15
影响因子：
11.1
作者：
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作者：
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影响因子：
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作者：
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影响因子：
4.4
作者：
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通讯作者：
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