title: Characterization of sequence variations in immunodominant regions of the HBV-nucleocapsid protein as a prerequisite for the development of an epitope-based vaccine.
abstract: OBJECTIVE
  In hepatitis B virus infection, viral elimination is dependent on an efficient antiviral T cell response which is not detectable in chronic hepatitis B. Therefore, new therapeutic concepts focus on T cell activation, such as epitope-based T cell-targeted vaccines. However, with the development of peptide-based vaccines in mind, viral mutations frequently described in hepatitis B within known immunodominant helper epitopes may have an influence on peptide selection.
  
  
  METHODS
  Mutant peptides within immunodominant epitopes (aa 1-20, aa 91-105, and aa 143-157) at position 12, 14, 93, 97, 147, 151, 153, and 155 were tested with peripheral blood mononuclear and specific clone cells for their ability to induce proliferation, produce cytokines, induce T cell receptor down-regulation or antagonize wild-type activity of the hepatitis B core antigen-specific CD4+ T cell clones.
  
  
  RESULTS
  Five variants could not induce T cell proliferation or cytokine production when the variants were presented alone. Coincubation with wild-type epitopes leads to T cell activation showing that the variants do not act as T cell receptor antagonists for hepatitis B virus-specific CD4+ T cells. In contrast, five other variants and wild-type peptides stimulated CD4+ T cell proliferation and production of Th1 cytokines.
  
  
  CONCLUSIONS
  Our data demonstrate that frequently occurring mutations within immunodominant epitopes have rather a nonstimulatory than a strengthening effect and thus should not included in a vaccine.
authors.affiliation: Department of Internal Medicine II, Klinikum Grosshadern, University of Munich, Marchioninistrasse 15, 81377 Munich, Germany.
authors.forename: Norbert H
authors.initials: NH
authors.lastname: Gruener
authors.forename: Tilman J
authors.initials: TJ
authors.lastname: Gerlach
authors.forename: Axel
authors.initials: A
authors.lastname: Ulsenheimer
authors.forename: Helmut M
authors.initials: HM
authors.lastname: Diepolder
authors.forename: Eddy
authors.initials: E
authors.lastname: Wierenga
authors.forename: Reinhart
authors.initials: R
authors.lastname: Zachoval
authors.forename: Malte
authors.initials: M
authors.lastname: Heeg
authors.forename: Gerd Rudolf
authors.initials: GR
authors.lastname: Pape
authors.forename: Maria-Christina
authors.initials: MC
authors.lastname: Jung
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002999:Clone Cells; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D000939:Epitopes / Q000276:immunology*; D005434:Flow Cytometry; D006509:Hepatitis B / Q000473:pathology; D006514:Hepatitis B Surface Antigens / Q000235:genetics; D017325:Hepatitis B Vaccines / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009154:Mutation / Q000235:genetics / Q000502:physiology; D019590:Nucleocapsid Proteins / Q000235:genetics* / Q000276:immunology* / Q000494:pharmacology; D010455:Peptides / Q000235:genetics / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000235:genetics
chemical_list: D016207:Cytokines; D000939:Epitopes; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D019590:Nucleocapsid Proteins; D010455:Peptides; D011948:Receptors, Antigen, T-Cell