title: Ubiquitin-modified hepatitis B virus core antigen effectively facilitates antigen presentation and enhances cytotoxic T lymphocyte activity via the cytoplasmic transduction peptide in vitro.
abstract: Cluster of differentiation (CD)8+ cytotoxic T lymphocytes (CTLs) have a key role in the elimination of hepatitis B virus (HBV)-infected cells. Ubiquitin (Ub) functions as a marker for protein degradation, which may promote the generation of peptides appropriate for major histocompatibility complex class I presentation, while the HBV core antigen (HBcAg) possesses marked immunogenic properties. However, it remains to be elucidated whether Ub-modified HBcAg is able to effectively elicit significant CD8+ CTL activity. In order to address this issue, a prokaryotic vector was constructed to express the Ub-HBcAg-cytoplasmic transduction peptide (CTP). The fusion protein was successfully expressed and subsequently pulsed into bone-marrow-derived dendritic cells (DCs). It was confirmed that with assistance from the cell‑penetrating properties of CTP, the fusion protein was able to directly penetrate into the cytoplasm of DCs. The results revealed that the Ub-HBcAg-CTP fusion protein not only increased the expression of surface molecules in DCs and cytokine secretion from proliferating T cells, but also induced T cells to differentiate into specific CTLs and enhanced their antiviral ability. In conclusion, the Ub-HBcAg-CTP fusion protein promoted DC maturation, enhanced the presentation of targeting antigens and efficiently induced HBcAg‑specific CTL immune responses in vitro.
authors: Department of Infectious Disease, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
authors: Linlin
authors: L
authors: Song
authors: Department of Infectious Disease, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
authors: Meng
authors: M
authors: Zhuo
authors: Department of Infectious Disease, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
authors: Yuyan
authors: Y
authors: Tang
authors: Department of Infectious Disease, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
authors: Xiaohua
authors: X
authors: Chen
authors: Department of Infectious Disease, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
authors: Yongsheng
authors: Y
authors: Yu
authors: Department of Infectious Disease, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
authors: Zhenghao
authors: Z
authors: Tang
authors: Department of Infectious Disease, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
authors: Guoqing
authors: G
authors: Zang
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D049109:Cell Proliferation; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D057809:HEK293 Cells; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006515:Hepatitis B virus / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000276:immunology / Q000302:isolation & purification; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D025801:Ubiquitin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D006512:Hepatitis B Core Antigens; D010455:Peptides; D011993:Recombinant Fusion Proteins; D025801:Ubiquitin; D018664:Interleukin-12; D007371:Interferon-gamma