National Institute for Communicable Diseases, Johannesburg, South Africa.
J Acquir Immune Defic Syndr. 2011 Jul 1;57(3):181-9. doi: 10.1097/QAI.0b013e3182174a76.
What characterizes individuals whose natural killer (NK) cells are able to respond to HIV-1 peptides is not known.
The association between NK cell responses and KIR gene profiles and HLA-B and HLA-C alleles was investigated among 76 HIV-1-infected women in South Africa previously categorized as responders (n = 39) or nonresponders (n = 37) to HIV-1 peptide pools in a whole blood intracellular cytokine assay. Viral load was significantly lower and CD4 T-cell counts higher among responders compared with nonresponders (P = 0.023 and P = 0.030, respectively).
Possession of one HLA-C1 allele associated with increased magnitude of NK cell responses to Env (P = 0.031) and significantly decreased viral load (P = 0.027) compared with its absence. There was a trend to increased possession of KIR2DL3+HLA-C1 in responders (71.8% vs 51.4%, P = 0.098) and decreased possession of KIR2DL3/2DL3+C2C2 (2.6% vs 16.2%, P = 0.053). A total of 64.1% of responders versus 32.4% of nonresponders had 13 or more KIR genes (P = 0.0067). Notably, the 13-KIR gene containing the Bx21 genotype (has eight inhibitory and three activating genes KIR2DS2, 2DS4, 2DS5) showed substantially higher representation among the responders (28.2% vs 2.6%, P = 0.001). A significantly higher proportion of responders had both KIR2DS2 and KIR2DS5 compared with either gene alone (72.4% vs 37%; P = 0.015). At least one HLA-C1 allele together with 13 or more KIR genes was associated with NK cell responsiveness (48.7% vs 13.5%; P = 0.001).
NK cell responses to HIV-1 peptides are more likely to occur among individuals with a genotype supporting a more activating NK cell phenotype and who possess at least one HLA-C1 allele.
目前尚不清楚哪些特征可以使自然杀伤 (NK) 细胞能够对 HIV-1 肽产生反应。
本研究在南非的 76 名 HIV-1 感染者中调查了 NK 细胞反应与 KIR 基因谱以及 HLA-B 和 HLA-C 等位基因之间的关联，这些感染者此前根据其在全血细胞内细胞因子检测中对 HIV-1 肽池的反应被分为应答者（n=39）和无应答者（n=37）。与无应答者相比，应答者的病毒载量显著较低，CD4 T 细胞计数较高（分别为 P=0.023 和 P=0.030）。
与缺乏 HLA-C1 等位基因相比，携带一个 HLA-C1 等位基因与 Env 刺激的 NK 细胞反应幅度增加（P=0.031）以及病毒载量显著降低（P=0.027）相关。与无应答者相比，应答者中 KIR2DL3+HLA-C1 的携带率呈增加趋势（71.8%比 51.4%，P=0.098），而 KIR2DL3/2DL3+C2C2 的携带率呈降低趋势（2.6%比 16.2%，P=0.053）。与无应答者相比，应答者中 13 个或更多 KIR 基因的比例更高（64.1%比 32.4%，P=0.0067）。值得注意的是，含有 Bx21 基因型（具有 8 个抑制性和 3 个激活基因 KIR2DS2、2DS4、2DS5）的 13-KIR 基因的应答者比例显著更高（28.2%比 2.6%，P=0.001）。与仅携带一个 KIR2DS2 或 KIR2DS5 基因的应答者相比，同时携带 KIR2DS2 和 KIR2DS5 的应答者比例更高（72.4%比 37%，P=0.015）。至少一个 HLA-C1 等位基因与 13 个或更多 KIR 基因共同存在与 NK 细胞反应性相关（48.7%比 13.5%，P=0.001）。
在具有支持更激活的 NK 细胞表型的基因型的个体中，更有可能发生对 HIV-1 肽的 NK 细胞反应，且这些个体至少携带一个 HLA-C1 等位基因。
