Priming of cytotoxic T cell responses to exogenous hepatitis B virus core antigen is B cell dependent

J Gen Virol. 2003 Jan;84(Pt 1):139-146. doi: 10.1099/vir.0.18678-0.


The hepatitis B virus (HBV) core antigen (HBcAg) has a unique ability to bind a high frequency of naive human and murine B cells. The role of HBcAg-binding naive B cells in the immunogenicity of HBcAg is not clear. The HBcAg-binding properties of naive B cells were characterized using HBcAg particles with mutated spike region (residues 76-85) sequences. Deletion of residues 76-85 (HBcDelta76-85) destroyed naive B cell binding, whereas deletion of residues 79-85 did not. HBcAg particles with an Ile instead of the natural Ala at position 80 did not bind naive B cells, whereas reversion of Ile80-->Ala restored B cell binding. Destroying the B cell-binding ability of HBcAg had a marginal effect on the overall B cell immunogenicity of the different particles, suggesting that they were equally efficient in priming T helper cells. Therefore, the importance of HBcAg-binding B cells is studied with relation to the priming of HBcAg-specific cytotoxic T cells (CTLs). The role of HBcAg-binding B cells in the priming of HBcAg-specific CTLs was evaluated by immunization with endogenous HBcAg (DNA immunization) and exogenous recombinant HBcAg particles. Endogenous HBcAg primed HBcAg-specific CTLs in wild-type and B cell-deficient mice, whereas exogenous HBcAg primed HBcAg-specific CTLs only in wild-type mice. Importantly, HBcDelta76-85 did not prime CTLs despite the presence of B cells. Thus, the ability of exogenous HBcAg particles to prime specific CTLs is B cell dependent, suggesting a possible role for HBcAg-binding B cells in HBV infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Binding Sites
  • Hepatitis B / immunology
  • Hepatitis B / prevention & control
  • Hepatitis B Antibodies / blood
  • Hepatitis B Core Antigens / chemistry*
  • Hepatitis B Core Antigens / genetics
  • Hepatitis B Core Antigens / immunology*
  • Hepatitis B Core Antigens / metabolism
  • Hepatitis B Vaccines / immunology
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology*
  • Immunization
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Recombinant Proteins / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Vaccines, Synthetic
  • Virion / immunology


  • Hepatitis B Antibodies
  • Hepatitis B Core Antigens
  • Hepatitis B Vaccines
  • Recombinant Proteins
  • Vaccines, Synthetic