title: Priming of cytotoxic T cell responses to exogenous hepatitis B virus core antigen is B cell dependent.
abstract: 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.
authors.affiliation: Division of Clinical Virology, F68, Karolinska Institutet at Huddinge University Hospital, S 141 86 Stockholm, Sweden.
authors.forename: Una
authors.initials: U
authors.lastname: Lazdina
authors.affiliation: Division of Clinical Virology, F68, Karolinska Institutet at Huddinge University Hospital, S 141 86 Stockholm, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Alheim
authors.affiliation: Division of Clinical Virology, F68, Karolinska Institutet at Huddinge University Hospital, S 141 86 Stockholm, Sweden.
authors.forename: Jessica
authors.initials: J
authors.lastname: Nyström
authors.affiliation: Division of Clinical Virology, F68, Karolinska Institutet at Huddinge University Hospital, S 141 86 Stockholm, Sweden.
authors.forename: Catharina
authors.initials: C
authors.lastname: Hultgren
authors.affiliation: Biomedical Research and Study Center, University of Latvia, Riga, Latvia.
authors.forename: Gallina
authors.initials: G
authors.lastname: Borisova
authors.affiliation: Biomedical Research and Study Center, University of Latvia, Riga, Latvia.
authors.forename: Irina
authors.initials: I
authors.lastname: Sominskaya
authors.affiliation: Biomedical Research and Study Center, University of Latvia, Riga, Latvia.
authors.forename: Paul
authors.initials: P
authors.lastname: Pumpens
authors.affiliation: Department of Biochemistry, Commonwealth University, Richmond, VA, USA.
authors.forename: Darrell L
authors.initials: DL
authors.lastname: Peterson
authors.affiliation: Vaccine Research Institute of San Diego, San Diego, CA, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Milich
authors.affiliation: Division of Clinical Virology, F68, Karolinska Institutet at Huddinge University Hospital, S 141 86 Stockholm, Sweden.
authors.forename: Matti
authors.initials: M
authors.lastname: Sällberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001665:Binding Sites; D006509:Hepatitis B / Q000276:immunology / Q000517:prevention & control; D006510:Hepatitis B Antibodies / Q000097:blood; D006512:Hepatitis B Core Antigens / Q000737:chemistry* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017325:Hepatitis B Vaccines / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014614:Vaccines, Synthetic; D014771:Virion / Q000276:immunology
chemical_list: D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D017325:Hepatitis B Vaccines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic