Long L, Jia M, Fan X, Liang H, Wang J, Zhu L, Xie Z, Shen T
Department of Laboratory Medicine, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University, Beijing, China.
Clin Exp Immunol. 2017 Jul;189(1):92-102. doi: 10.1111/cei.12962. Epub 2017 Apr 7.
Natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (NK-ADCC) is of considerable interest in viral infection. However, little is known about NK-ADCC responses in chronic hepatitis C virus (HCV) infection. In this study, impaired non-specific antibody-dependent CD56 NK cell responses were observed in chronic HCV infection, as shown by decreased degranulation (extracellular CD107a expression) and interferon (IFN)-γ production in response to antibody-bound P815 cells. A peptide pool composed of epitopes recognized by anti-HCV-E1/E2 antibodies could induce pronounced HCV-specific antibody-dependent NK cell responses in sera from approximately half the chronic HCV carriers. Additionally, HCV-specific epitopes with the capacity to induce robust NK-ADCC activity were identified. Five linear NK-ADCC epitopes (aa211-aa217, aa384-aa391, aa464-aa475, aa544-aa551 and aa648-aa659 of the HCV envelope) were identified and do not overlap with putative linear neutralizing epitopes. This study revealed the dysfunctional characteristics of antibody-dependent CD56 NK cell responses in chronic HCV carriers. The key non-neutralizing NK-ADCC epitopes identified in this study may act as new targets for immunological intervention.
自然杀伤（NK）细胞介导的抗体依赖性细胞毒性作用（NK-ADCC）在病毒感染中备受关注。然而，关于慢性丙型肝炎病毒（HCV）感染中的NK-ADCC反应，我们所知甚少。在本研究中，观察到慢性HCV感染中存在非特异性抗体依赖性CD56 NK细胞反应受损的情况，这表现为与抗体结合的P815细胞刺激后脱颗粒减少（细胞外CD107a表达降低）以及干扰素（IFN）-γ产生减少。由抗HCV-E1/E2抗体识别的表位组成的肽池可在约一半慢性HCV携带者的血清中诱导明显的HCV特异性抗体依赖性NK细胞反应。此外，还鉴定出了具有诱导强大NK-ADCC活性能力的HCV特异性表位。确定了五个线性NK-ADCC表位（HCV包膜的aa211-aa217、aa384-aa391、aa464-aa475、aa544-aa551和aa648-aa659），它们与推定的线性中和表位不重叠。本研究揭示了慢性HCV携带者中抗体依赖性CD56 NK细胞反应的功能失调特征。本研究中确定的关键非中和性NK-ADCC表位可能成为免疫干预的新靶点。
