Identification of novel HLA-DR1-restricted epitopes from the hepatitis B virus envelope protein in mice expressing HLA-DR1 and vaccinated human subjects

• Published in: Microbes and infection Vol. 8; no. 12; pp. 2783 - 2790
• Main Authors: Pajot, Anthony, Michel, Marie-Louise, Mancini-Bourgine, Maryline, Ungeheuer, Marie-Noelle, Ojcius, David M., Deng, Qiang, Lemonnier, François A., Lone, Yu-Chun
• Format: Journal Article
• Language: English
• Published: Lausanne Elsevier SAS 01.10.2006; Amsterdam Elsevier; Paris
• Subjects: Adolescent; Adult; Animals; Applied microbiology; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; Epitope Mapping; Epitopes, T-Lymphocyte - immunology; Female; Fundamental and applied biological sciences. Psychology; HBsAg; Hepatitis B; Hepatitis B - immunology; Hepatitis B Surface Antigens - immunology; Hepatitis B Vaccines - immunology; Hepatitis B virus; Hepatitis B virus - immunology; HLA-DR1; HLA-DR1 Antigen - genetics; HLA-DR1 Antigen - immunology; Human viral diseases; Humans; Infectious diseases; Lymphocyte Activation; Medical sciences; Mice; Mice, Transgenic; Microbiology; Middle Aged; Miscellaneous; T-cell epitope; T-Lymphocytes, Helper-Inducer - immunology; Transgenic mice; Vaccine; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, DNA - immunology; Viral diseases; Viral Envelope Proteins - immunology; Viral hepatitis; Virology; HTL; T-cell epitope; Transgenic mice; HBsAg; HLA-DR1; Vaccine; PBMC; SI; mIU; HBcAg; CTL; HCV; HBV; Hepatitis B; HIV 1; HLA-System; Antigenic determinant; Orthohepadnavirus; Transgenic animal; Hepatic disease; Identification; Viral hepatitis B; Hepadnaviridae; T-Lymphocyte; Hepatitis B virus; Human; Hepatitis B surface antigen; Rodentia; Protein; Infection; Virus; Vertebrata; Mammalia; Mouse; Viral disease; Digestive diseases
• ISSN: 1286-4579; 1769-714X
• DOI: 10.1016/j.micinf.2006.08.009

Helper T lymphocytes that control CD8 + T-cell and antibody responses are key elements for the resolution of infection by the hepatitis B virus and for the development of effective immunological memory after hepatitis B vaccination. We have used H-2 class II-deficient mice that express the human MHC class II molecule, HLA-DR1, to identify novel hepatitis B virus envelope-derived T helper epitopes. We confirmed the immunogenicity of a previously described HLA-DR1-restricted epitope, and identified three novel epitopes. CD4 + T-cell immune responses against these epitopes were detected in peripheral blood mononuclear cells from HLA-DR1 + individuals vaccinated against hepatitis B. We showed that subjects receiving the currently available hepatitis B vaccines do not develop cross-reactive T helper responses against one of the novel epitopes which are structurally variable between different hepatitis B virus subtypes. These findings highlight the need for developing vaccines against a wider range of viral subtypes, and establish humanized mice as a convenient tool for identifying new immunogenic epitopes from pathogens.