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

作者：Chen, Lubiao; Zhang, Ying; Zhang, Shaoquan; Chen, Youming; Shu, Xin; Lai, Jing; Cao, Hong; Lian, Yifan; Stamataki, Zania; Huang, Yuehua^*

来源：Archives of Virology, 2019, 164(2): 483-495.

DOI：10.1007/s00705-018-4095-0

• TENOFOVIR DISOPROXIL FUMARATE
• HEPATOCELLULAR-CARCINOMA
• TUMOR LYSATE
• PHASE-I/II
• ANTIGEN
• IMMUNOTHERAPY
• ENTECAVIR
• IMMUNODOMINANCE
• ELIMINATE
• EFFICACY

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--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.

• 出版日期2019-2
• 单位中山大学