Epitopes described in "Multiepitopic HLA-A*0201-restricted immune response against hepatitis B surface antigen after DNA-based immunization."

Article Authors:D Loirat; F A Lemonnier; M L Michel
Article Title:Multiepitopic HLA-A*0201-restricted immune response against hepatitis B surface antigen after DNA-based immunization.
Reference Detail
Reference ID:315589
Abstract:CTL together with anti-envelope Abs represent major effectors for viral clearance during hepatitis B virus (HBV) infection. The induction of strong cytotoxic and Ab responses against the envelope proteins after DNA-based immunization has been proposed as a promising therapeutic approach to mediate viral clearance in chronically infected patients. Here, we studied the CTL responses against previously described hepatitis B surface Ag (HBsAg)-HLA-A*0201-restricted epitopes after DNA-based immunization in HLA-A*0201 transgenic mice. The animal model used was Human Human D(b) (HHD) mice, which are deficient for mouse MHC class I molecules (beta(2)-microglobulin(-/-) D(b-/-)) and transgenic for a chimeric HLA-A*0201/D(b) molecule covalently bound to the human beta(2)-microglobulin (HHD(+/+)). Immunization of these mice with a DNA vector encoding the small and the middle HBV envelope proteins carrying HBsAg induced CTL responses against several epitopes in each animal. This study performed on a large number of animals described dominant epitopes with specific CTL induced in all animals and others with a weaker frequency of recognition. These results confirmed the relevance of the HHD transgenic mouse model in the assessment of vaccine constructs for human use. Moreover, genetic immunization of HLA-A2 transgenic mice generates IFN-gamma-secreting CD8(+) T lymphocytes specific for endogenously processed peptides and with recognition specificities similar to those described during self-limited infection in humans. This suggests that responses induced by DNA immunization could have the same immune potential as those developing during natural HBV infection in human patients.
Affiliations:Unité de Recombinaison et Expression Génétique, Institut National de la Santé et de la Recherche Médicale, Unité 163, Institut Pasteur, Paris, France.
Reference Type:Literature
PubMed ID:11035120
Journal:J Immunol
Journal Volume:165
Article Pages:4748-55
Journal ISSN:0022-1767
Article Chemical List:Epitopes, T-Lymphocyte;HLA-A2 Antigen;Hepatitis B Surface Antigens;Hepatitis B Vaccines;Vaccines, DNA;Viral Envelope Proteins;Interferon-gamma
Article MeSH List:Alleles; Animals; Antigen Presentation(genetics); CD8-Positive T-Lymphocytes(immunology; secretion); Cytotoxicity, Immunologic(genetics); Epitopes, T-Lymphocyte(genetics; immunology; metabolism); Female; HLA-A2 Antigen(genetics; immunology); Hepatitis B Surface Antigens(immunology); Hepatitis B Vaccines(genetics; immunology); Hepatitis B virus(genetics; immunology); Humans; Interferon-gamma(secretion); Mice; Mice, Transgenic; Protein Binding(genetics; immunology); T-Lymphocytes, Cytotoxic(immunology; metabolism); Vaccines, DNA(genetics; immunology); Viral Envelope Proteins(biosynthesis; genetics; immunology; metabolism)
Article Comments:Data originally imported from the HLA Ligand Database (http://hlaligand.ouhsc.edu/)
Curation Last Updated:2015-06-30 20:01:38