PMID- 30415392 OWN - NLM STAT- MEDLINE DCOM- 20190219 LR - 20200225 IS - 1432-8798 (Electronic) IS - 0304-8608 (Print) IS - 0304-8608 (Linking) VI - 164 IP - 2 DP - 2019 Feb TI - A novel T-cell epitope in the transmembrane region of the hepatitis B virus envelope protein responds upon dendritic cell expansion. PG - 483-495 LID - 10.1007/s00705-018-4095-0 [doi] AB - Restoring antiviral immunity is a promising immunotherapeutic approach to the treatment of chronic hepatitis B virus (HBV) infection. Dendritic cells play a crucial role in triggering antiviral immunity. In this study, we identified immunodominant epitopes prevalent in CD8(+) T cell responses. We characterized the hierarchy of HBV epitopes targeted by CD8(+) T cells following autologous monocyte-derived dendritic cell (moDC) expansion in HBV-infected subjects with distinct disease stages: treatment-naive (TN group, n = 168), treatment with complete virological response (TR group, n = 72), and resolved HBV infection (RS group, n = 28). T cell responses against 32 HBV epitopes were measured upon moDC expansion. Several subdominant epitopes that triggered HBV-specific CD8(+) T cell responses were identified. These epitopes' responses varied in individuals with different disease stages. Moreover, the most immunodominant and immunoprevalent epitope included the envelope residues 256-270 (Env(256-270)), corresponding to amino acid residues 93-107 in the small HBV surface protein (SHBs) across three patient groups. The frequency of Env(256-270)-specific interferon-gamma-producing T cells was the highest in the RS group and the lowest in the TN group. In addition, individuals with HLA-A*02:03/02:06/02:07 were capable of responding to Env(256-270). Env(256-270)-specific CD8(+) T cells tolerated amino acid variations within the epitope detected in HBV genotypes B and C. This suggests that Env(256-270) in SHBs is crucial in HBV-specific T cell immunity following autologous moDC expansion. It might be a potential target epitope for dendritic-cell-based immunotherapy for CHB patients with complete viral suppression by long-term NAs treatment. FAU - Chen, Lubiao AU - Chen L AD - Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, China. FAU - Zhang, Ying AU - Zhang Y AD - Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, China. FAU - Zhang, Shaoquan AU - Zhang S AD - Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, China. FAU - Chen, Youming AU - Chen Y AD - Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, China. FAU - Shu, Xin AU - Shu X AD - Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, China. FAU - Lai, Jing AU - Lai J AD - Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, China. FAU - Cao, Hong AU - Cao H AD - Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, China. FAU - Lian, Yifan AU - Lian Y AD - Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. FAU - Stamataki, Zania AU - Stamataki Z AD - National Institute for Health Research Birmingham Liver Biomedical Research Unit, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK. FAU - Huang, Yuehua AU - Huang Y AD - Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, China. huangyh53@mail.sysu.edu.cn. AD - Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. huangyh53@mail.sysu.edu.cn. LA - eng GR - 2016201604030021/International Cooperation Project of Guangzhou Science and Technology Program/ GR - 2014ZX10002002-002/National Grant Program on Key Infectious Disease/ PT - Journal Article DEP - 20181110 PL - Austria TA - Arch Virol JT - Archives of virology JID - 7506870 RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (Hepatitis B Surface Antigens) RN - 0 (Immunodominant Epitopes) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Adult MH - CD8-Positive T-Lymphocytes/cytology/immunology/virology MH - Cell Differentiation MH - Cell Proliferation MH - Cells, Cultured MH - Dendritic Cells/chemistry/cytology/*immunology MH - Epitope Mapping MH - Epitopes, T-Lymphocyte/chemistry/genetics/*immunology MH - Female MH - Hepatitis B/genetics/*immunology/physiopathology/virology MH - Hepatitis B Surface Antigens/chemistry/genetics/*immunology MH - Hepatitis B virus/chemistry/genetics/*immunology MH - Humans MH - Immunodominant Epitopes/chemistry/genetics/immunology MH - Interferon-gamma/genetics/immunology MH - Male MH - Middle Aged MH - Monocytes/cytology/immunology MH - Young Adult PMC - PMC6373280 COIS- CONFLICT OF INTEREST: The authors declare that they have no conflict of interest. ETHICAL APPROVAL: The study was approved by the Ethical Committee of the Sun Yat-sen University. INFORMED CONSENT: Written informed consents were obtained from all subjects in this study. EDAT- 2018/11/12 06:00 MHDA- 2019/03/21 06:00 PMCR- 2018/11/10 CRDT- 2018/11/12 06:00 PHST- 2018/04/17 00:00 [received] PHST- 2018/10/21 00:00 [accepted] PHST- 2018/11/12 06:00 [pubmed] PHST- 2019/03/21 06:00 [medline] PHST- 2018/11/12 06:00 [entrez] PHST- 2018/11/10 00:00 [pmc-release] AID - 10.1007/s00705-018-4095-0 [pii] AID - 4095 [pii] AID - 10.1007/s00705-018-4095-0 [doi] PST - ppublish SO - Arch Virol. 2019 Feb;164(2):483-495. doi: 10.1007/s00705-018-4095-0. Epub 2018 Nov 10.