title: Diversity of core antigen epitopes of hepatitis B virus.
abstract: Core antigen (cAg), the viral capsid, is one of the three major clinical antigens of hepatitis B virus. cAg has been described as presenting either one or two conformational epitopes involving the "immunodominant loop." We have investigated cAg antigenicity by cryo-electron microscopy at approximately 11-A resolution of capsids labeled with monoclonal Fabs, combined with molecular modeling, and describe here two conformational epitopes. Both Fabs bind to the dimeric external spikes, and each epitope has contributions from the loops on both subunits, explaining their discontinuous nature: however, their binding aspects and epitopes differ markedly. To date, four cAg epitopes have been characterized: all are distinct. Although only two regions of the capsid surface are accessible to antibodies, local clustering of the limited number of exposed peptide loops generates a potentially extensive set of discontinuous epitopes. This diversity has not been evident from competition experiments because of steric interference effects. These observations suggest an explanation for the distinction between cAg and e-antigen (an unassembled form of capsid protein) and an approach to immunodiagnosis, exploiting the diversity of cAg epitopes.
authors.affiliation: Laboratory of Structural Biology and Protein Expression Laboratory, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Belnap
authors.forename: N R
authors.initials: NR
authors.lastname: Watts
authors.forename: J F
authors.initials: JF
authors.lastname: Conway
authors.forename: N
authors.initials: N
authors.lastname: Cheng
authors.forename: S J
authors.initials: SJ
authors.lastname: Stahl
authors.forename: P T
authors.initials: PT
authors.lastname: Wingfield
authors.forename: A C
authors.initials: AC
authors.lastname: Steven
mesh_terms: D020285:Cryoelectron Microscopy; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D008958:Models, Molecular
chemical_list: D000939:Epitopes; D006512:Hepatitis B Core Antigens