A novel T-cell epitope in the transmembrane region of the hepatitis B virus envelope protein responds upon dendritic cell expansion

Arch Virol. 2019 Feb;164(2):483-495. doi: 10.1007/s00705-018-4095-0. Epub 2018 Nov 10.


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-naïve (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 (Env256-270), corresponding to amino acid residues 93-107 in the small HBV surface protein (SHBs) across three patient groups. The frequency of Env256-270-specific interferon-γ-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 Env256-270. Env256-270-specific CD8+ T cells tolerated amino acid variations within the epitope detected in HBV genotypes B and C. This suggests that Env256-270 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.

MeSH terms

  • Adult
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / virology
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Dendritic Cells / chemistry
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Epitope Mapping
  • Epitopes, T-Lymphocyte / chemistry
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Hepatitis B / genetics
  • Hepatitis B / immunology*
  • Hepatitis B / physiopathology
  • Hepatitis B / virology
  • Hepatitis B Surface Antigens / chemistry
  • Hepatitis B Surface Antigens / genetics
  • Hepatitis B Surface Antigens / immunology*
  • Hepatitis B virus / chemistry
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology*
  • Humans
  • Immunodominant Epitopes / chemistry
  • Immunodominant Epitopes / genetics
  • Immunodominant Epitopes / immunology
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Male
  • Middle Aged
  • Monocytes / cytology
  • Monocytes / immunology
  • Young Adult


  • Epitopes, T-Lymphocyte
  • Hepatitis B Surface Antigens
  • Immunodominant Epitopes
  • Interferon-gamma