Increased frequency and function of KIR2DL1-3⁺ NK cells in primary HIV-1 infection are determined by HLA-C group haplotypes.
Increased frequency and function of KIR2DL1-3⁺ NK cells in primary HIV-1 infection are determined by HLA-C group haplotypes.
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HLA-C组单倍型确定原发性HIV-1感染中KIR2DL1-3⁺NK细胞的频率和功能的增加。
DOI：
10.1002/eji.201444751
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发表时间：
2014-10
影响因子：
5.4
通讯作者：
Altfeld, Marcus
中科院分区：
文献类型：
--
作者：
Koerner, Christian;Granoff, Mitchell E.;Amero, Molly A.;Sirignano, Michael N.;Vaidya, Sagar A.;Jost, Stephanie;Allen, Todd M.;Rosenberg, Eric S.;Altfeld, Marcus
NK细胞功能的获得和维持由抑制性免疫球蛋白样受体（KIR）通过与HLA I类分子的相互作用介导。最近，HLA-C表达水平被证明与保护免受HIV-1感染的多种结果相关;然而，对其潜在机制知之甚少。由于HLA-C是抑制性受体KIR 2DL 1和KIR 2DL 2/3的天然配体，我们试图确定HLA-C组单倍型是否影响原发性HIV-1感染期间的NK细胞应答。评估了来自HIV-1（+）和HIV-1（-）个体的NK细胞的表型和功能能力（分别为N=42和N=40）。HIV-1感染与KIR 2DL 1 -3+ NK细胞频率增加相关。进一步的分析显示，KIR 2DL 1 + NK细胞在HLA-C2纯合子个体中选择性增加，而HLA-C1纯合子个体显示KIR 2DL 2/3+ NK细胞比例增加。此外，通过脱粒和细胞因子产生测量，在也编码其同源HLA-C组单倍型的个体中，KIR 2DL 1 -3+ NK细胞在原发性HIV-1感染期间更具多功能性。这些结果确定了HLA-C和KIR 2DL + NK细胞亚群之间的新关系，并证明HLA-C介导的许可调节NK细胞对原发性HIV-1感染的应答。
Acquisition and maintenance of NK cell function is mediated by inhibitory killer-cell immunoglobulin-like receptors (KIR) through the interaction with HLA class I molecules. Recently, HLA-C expression levels were shown to be correlated with protection against multiple outcomes of HIV-1 infection; however the underlying mechanisms are poorly understood. As HLA-C is the natural ligand for the inhibitory receptors KIR2DL1 and KIR2DL2/3, we sought to determine whether HLA-C group haplotypes affect NK cell responses during primary HIV-1 infection. The phenotypes and functional capacity of NK cells derived from HIV-1(+) and HIV-1(-) individuals were assessed (N=42 and N=40, respectively). HIV-1 infection was associated with an increased frequency of KIR2DL1-3+ NK cells. Further analysis showed that KIR2DL1+ NK cells were selectively increased in individuals homozygous for HLA-C2, while HLA-C1-homozygous individuals displayed increased proportions of KIR2DL2/3+ NK cells. KIR2DL1-3+ NK cells were furthermore more polyfunctional during primary HIV-1 infection in individuals also encoding for their cognate HLA-C group haplotypes as measured by degranulation and cytokine production. These results identify a novel relationship between HLA-C and KIR2DL+ NK cell subsets and demonstrate that HLA-C-mediated licensing modulates NK cell responses to primary HIV-1 infection.
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影响因子：
6.7
作者：
Fadda L;Körner C;Kumar S;van Teijlingen NH;Piechocka-Trocha A;Carrington M;Altfeld M
通讯作者：
Altfeld M
影响因子：
4.4
作者：
Falco, Michela;Romeo, Elisa;Pende, Daniela
通讯作者：
Pende, Daniela
影响因子：
5
作者：
Czaja, K.;Borer, A-S;Gonzalez, A.
通讯作者：
Gonzalez, A.
统一依赖MHC的天然杀手细胞教育的概念。
影响因子：
16.8
作者：
Elliott JM;Yokoyama WM
通讯作者：
Yokoyama WM
影响因子：
8.6
作者：
Kamya, Philomena;Talton, Benjamin;Bernard, Nicole F.
通讯作者：
Bernard, Nicole F.