title: Different immunogenicity of H-2 Kb-restricted epitopes in natural variants of the hepatitis B surface antigen.
abstract: The small hepatitis B surface antigen (HBsAg) of hepatitis B virus (HBV) has limited variability, but some serotypes and genotypes have been defined. Although no biological or pathogenetic differences could be traced to HBV serotypes, the clinical picture, response to treatment and long-term prognosis of HBV infection may vary with the HBV genotype, possibly due to differences in specific T cell recognition of HBV antigens from different genotypes. We analyzed murine CD8(+) T cell responses to two K(b)-restricted HBsAg epitopes primed by four different HBsAg variants using protein- and DNA-based vaccination protocols. The K(b)-binding S(208-215) epitope 1 is processed from exogenous but not endogenous HBsAg. Variants of epitope 1 differing at two positions within the epitope (ILSPFLPL in ayw/adr versus IVSPFIPL in adw2) efficiently primed cross-reactive CD8(+) T cell responses. In contrast, the exchange of an N-terminal flanking residue (S to N) completely eliminated the immunogenicity of epitope 1. The K(b)-binding S(190-197) epitope 2 is processed from endogenous but not exogenous HBsAg. A single-residue exchange within the epitope (VWLSVIWM in ayw/adr versus VWLSAIWM in adw2) completely eliminated the immunogenicity of epitope 2. Single, conservative residue exchanges can thus give rise to diverging CD8(+) T cell repertoires, suggesting an impressive complexity and flexibility of the CD8(+) T cell repertoire to antigen variants from viruses with limited diversity.
authors.affiliation: Department of Medical Microbiology, University of Ulm, Ulm, Germany. reinhold@schirmbeck@medizin.uni-ulm.de
authors.forename: Reinhold
authors.initials: R
authors.lastname: Schirmbeck
authors.forename: Waltraud
authors.initials: W
authors.lastname: Böhm
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fissolo
authors.forename: Karl
authors.initials: K
authors.lastname: Melber
authors.forename: Jörg
authors.initials: J
authors.lastname: Reimann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D014644:Genetic Variation; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D019444:Vaccines, DNA / Q000378:metabolism
chemical_list: D000939:Epitopes; D006514:Hepatitis B Surface Antigens; D019444:Vaccines, DNA