Impact of the MICA-129Met/Val Dimorphism on NKG2D-Mediated Biological Functions and Disease Risks.
Impact of the MICA-129Met/Val Dimorphism on NKG2D-Mediated Biological Functions and Disease Risks.
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DOI：
10.3389/fimmu.2016.00588
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发表时间：
2016
影响因子：
7.3
通讯作者：
Dressel R
中科院分区：
文献类型：
--
作者：
Isernhagen A;Malzahn D;Bickeböller H;Dressel R
主要组织相容性复合体（MHC）I类链相关A（云母）是人类中多态性最高的非经典MHC I类基因。它编码NKG 2D（NK组2，成员D）的配体，NKG 2D是一种活化自然杀伤（NK）受体，主要在NK细胞和CD 8 + T细胞上表达。引起云母蛋白129位缬氨酸（瓦尔）与甲硫氨酸（Met）交换的单核苷酸多态性（SNP）rs 1051792是特别感兴趣的。它将云母分离为以高亲和力（Met）和低亲和力（瓦尔）结合NKG 2D的亚型。因此，已经研究了这种SNP与感染、自身免疫性疾病和癌症的关联。在这里，我们系统地回顾这些研究，并分析他们的新数据，这种多态性的功能后果。最近已经表明，云母-129 Met变体激发更强的NKG 2D信号传导，导致NK细胞中更多的脱粒和IFN-γ产生，并且比云母-129 Val变体更快地共刺激CD 8 + T细胞。然而，云母-129 Met亚型也比云母-129 Val亚型更有效地下调NKG 2D。这种下调在MICA-Met变体的高表达强度下损害NKG 2D介导的功能。在解释疾病相关性研究时，需要考虑云母-129 Met/瓦尔二态性的这些特征。特别是在造血干细胞移植领域，它们有助于解释SNP与包括移植物抗宿主病和恶性肿瘤复发在内的结果的关联。未来的疾病相关性研究的云母-129 Met/瓦尔二态性的影响进行了讨论。
The major histocompatibility complex (MHC) class I chain-related A (MICA) is the most polymorphic non-classical MHC class I gene in humans. It encodes a ligand for NKG2D (NK group 2, member D), an activating natural killer (NK) receptor that is expressed mainly on NK cells and CD8+ T cells. The single-nucleotide polymorphism (SNP) rs1051792 causing a valine (Val) to methionine (Met) exchange at position 129 of the MICA protein is of specific interest. It separates MICA into isoforms that bind NKG2D with high (Met) and low affinities (Val). Therefore, this SNP has been investigated for associations with infections, autoimmune diseases, and cancer. Here, we systematically review these studies and analyze them in view of new data on the functional consequences of this polymorphism. It has been shown recently that the MICA-129Met variant elicits a stronger NKG2D signaling, resulting in more degranulation and IFN-γ production in NK cells and in a faster costimulation of CD8+ T cells than the MICA-129Val variant. However, the MICA-129Met isoform also downregulates NKG2D more efficiently than the MICA-129Val isoform. This downregulation impairs NKG2D-mediated functions at high expression intensities of the MICA-Met variant. These features of the MICA-129Met/Val dimorphism need to be considered when interpreting disease association studies. Particularly, in the field of hematopoietic stem cell transplantation, they help to explain the associations of the SNP with outcome including graft-versus-host disease and relapse of malignancy. Implications for future disease association studies of the MICA-129Met/Val dimorphism are discussed.
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DOI：
10.1084/jem.20081648
发表时间：
2009-04-13
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dai Z;Turtle CJ;Booth GC;Riddell SR;Gooley TA;Stevens AM;Spies T;Groh V
通讯作者：
Groh V
影响因子：
3.7
作者：
Chen K;Shi W;Xin Z;Wang H;Zhu X;Wu X;Li Z;Li H;Liu Y
通讯作者：
Liu Y
影响因子：
6.5
作者：
Antoun, Ayman;Vekaria, Dhruti;Moss, Paul
通讯作者：
Moss, Paul
影响因子：
4.1
作者：
Ashiru, Omodele;Lopez-Cobo, Sheila;Vales-Gomez, Mar
通讯作者：
Vales-Gomez, Mar
DOI：
10.1093/cid/civ540
发表时间：
2015-10-15
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Ayo CM;Oliveira AP;Camargo AV;Mattos CC;Bestetti RB;Mattos LC
通讯作者：
Mattos LC