Luxenburger Hendrik, Graß Franziska, Baermann Janina, Boettler Tobias, Marget Matthias, Emmerich Florian, Panning Marcus, Thimme Robert, Nitschke Katja, Neumann-Haefelin Christoph
Faculty of Medicine, Department of Medicine II, University Hospital Freiburg, University of Freiburg, Freiburg, Germany.
Institute of Transfusion Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
J Viral Hepat. 2018 Jul;25(7):779-790. doi: 10.1111/jvh.12874. Epub 2018 Feb 27.
Virus-specific CD8 T-cell responses play an important role in the outcome of hepatitis C virus (HCV) infection. To date, most HCV-specific CD8 T-cell epitopes have been defined in HCV genotype 1 infection. In contrast, the HCV genotype 4-specific CD8 T-cell response is poorly defined. Here, we analysed whether known HCV-specific CD8 T-cell epitopes are also recognized in HCV genotype 4-infected patients and set out to identify the first HCV genotype 4-specific CD8 T-cell epitopes. We studied patients chronically infected with HCV genotype 1 (n = 20) or 4 (n = 21) using 91 well-described HCV-specific epitope peptides. In addition, we analysed 24 genotype 4-infected patients using 40 epitope candidates predicted using an in silico approach. HCV-specific CD8 T-cell responses targeting previously described epitopes were detectable in the majority of genotype 1-infected patients (11 of 20). In contrast, patients infected with HCV genotype 4 rarely targeted these epitopes (4 of 21; P = .0247). Importantly, we were able to identify eight novel HCV genotype 4-specific CD8 T-cell epitopes. Only one of these epitopes was shared between genotype 1 and genotype 4. These results indicate that there is little overlap between CD8 T-cell repertoires targeting HCV genotype 1 and 4. Prophylactic vaccination studies based on HCV genotype 1 are currently underway. However, in countries with the highest prevalence of HCV infection, such as Egypt, most patients are infected with HCV genotype 4. Thus, prophylactic vaccination strategies need to be adapted to HCV genotype 4 before their application to regions where HCV genotype 4 is endemic.
病毒特异性CD8 T细胞反应在丙型肝炎病毒（HCV）感染的转归中起重要作用。迄今为止，大多数HCV特异性CD8 T细胞表位已在HCV 1型感染中得到明确。相比之下，HCV 4型特异性CD8 T细胞反应却鲜有明确。在此，我们分析了已知的HCV特异性CD8 T细胞表位在HCV 4型感染患者中是否也能被识别，并着手鉴定首个HCV 4型特异性CD8 T细胞表位。我们使用91种详细描述的HCV特异性表位肽研究了慢性感染HCV 1型（n = 20）或4型（n = 21）的患者。此外，我们使用通过计算机方法预测的40个表位候选物分析了24例HCV 4型感染患者。在大多数HCV 1型感染患者（20例中的11例）中可检测到针对先前描述表位的HCV特异性CD8 T细胞反应。相比之下，HCV 4型感染患者很少靶向这些表位（21例中的4例；P = 0.0247）。重要的是，我们能够鉴定出8个新的HCV 4型特异性CD8 T细胞表位。这些表位中只有1个在1型和4型之间共享。这些结果表明，靶向HCV 1型和4型的CD8 T细胞库之间几乎没有重叠。目前正在进行基于HCV 1型的预防性疫苗接种研究。然而，在HCV感染患病率最高的国家，如埃及，大多数患者感染的是HCV 4型。因此，预防性疫苗接种策略在应用于HCV 4型流行地区之前需要针对HCV 4型进行调整。
