Non-neutralizing epitopes induce robust hepatitis C virus (HCV)-specific antibody-dependent CD56+natural killer cell responses in chronic HCV-infected patients.
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.
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.
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L
Long
State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Center for AIDS/STD Control and Prevention, China CDC, Beijing, China.
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M
Jia
Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University, Beijing, China.
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X
Fan
State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Center for AIDS/STD Control and Prevention, China CDC, Beijing, China.
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H
Liang
Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China.
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J
Wang
Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University, Beijing, China.
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L
Zhu
Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University, Beijing, China.
Z
Z
Xie
Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University, Beijing, China.
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0000-0002-1365-9862
T
Shen
D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D016022:Case-Control Studies; D000939:Epitopes / Q000276:immunology; D005260:Female; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008875:Middle Aged
D000914:Antibodies, Viral; D000939:Epitopes; C573415:IFNG protein, human; D007371:Interferon-gamma
antibody-dependent cellular cytotoxicity; epitope; hepatitis C virus; natural killer cell; non-neutralizing antibody