Inhibitory Killer Immunoglobulin-like receptors to self HLA-B and HLA-C ligands contribute differentially to Natural Killer cell functional potential in HIV infected slow progressors

Inhibitory Killer Immunoglobulin-like receptors to self HLA-B and HLA-C ligands contribute differentially to Natural Killer cell functional potential in HIV infected slow progressors
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DOI:
10.1016/j.clim.2012.01.001
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发表时间:
2012-06-01
影响因子:
8.6
通讯作者:
Bernard, Nicole F.
Bernard, Nicole F.
中科院分区:
医学3区
文献类型:
--
作者:
Kamya, Philomena;Talton, Benjamin;Bernard, Nicole F.

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抑制性杀伤免疫球蛋白样受体(iKIR)与其配体HLA分子相互作用,以许可自然杀伤(NK)细胞的功能能力。先前用缺乏HLA的K562细胞系刺激外周血单核细胞(PBMC)的研究揭示,来自具有由KIR 3DL 1基因座编码的iKIR的个体的NK细胞以自身HLA-Bw 4作为其配体,具有较高频率的三功能NK细胞,表达脱粒标记物CD 107 a并分泌干扰素-γ和肿瘤坏死因子-γ。与来自HLA-Bw 6等位基因纯合个体的iKIR α相比,HLA-Bw 6等位基因不是这些iKIR的配体。为了评估其他针对自身HLA的iKIR(S-iKIR)对NK细胞应答的影响,我们比较了携带S-iKIR至HLA-C等位基因的HIV感染的缓慢进展者(SP),其具有或不具有针对HLA-Bw 4的S-iKIR。我们表明,S-iKIR HLA-B和C等位基因的不同,在HIV感染的SP与K562靶刺激后,他们的贡献NK细胞的功能潜力。(C)2012 Elsevier Inc. All rights reserved.
Inhibitory Killer Immunoglobulin-like Receptors (iKIR) interact with their ligands, HLA molecules, to license Natural Killer (NK) cells for functional competence. Previous studies stimulating peripheral blood mononuclear cells (PBMCs) with the HLA-devoid K562 cell line revealed that NK cells from individuals with an iKIR encoded by the KIR3DL1 locus with self HLA-Bw4 as their ligands, had higher frequencies of tri-functional NK cells that expressed the degranulation marker CD107a and secreted Interferon-gamma and Tumor Necrosis Factor-alpha than those from individuals who were homozygous for HLA-Bw6 alleles, which are not ligands for these iKIR. To assess the effect of other iKIR to self-HLA (S-iKIR) on the NK cell response, we compared HIV-infected slow progressors (SP) carrying S-iKIR to HLA-C alleles with or without S-iKIR to HLA-Bw4. We show that S-iKIR to HLA-B and C alleles differ in their contribution to NK cell functional potential in HIV-infected SP upon stimulation with K562 targets. (C) 2012 Elsevier Inc. All rights reserved.