Cryo-EM study of Hepatitis B virus core antigen capsids decorated with antibodies from a human patient

Eaazhisai Kandiah, Norman R. Watts, Naiqian Cheng, Giovanni Cardone, Stephen J. Stahl, Theo Heller, T. Jake Liang, Paul T. Wingfield, Alasdair C. Steven

Research output: Contribution to journalArticlepeer-review

Abstract

The capsid (core antigen, HBcAg) is one of three major antigens present in patients infected with Hepatitis B virus. The capsids are icosahedral particles, whose most prominent features are spikes that extend 25. å out from the contiguous "floor". At the spike tip are two copies of the "immunodominant loop". Previously, the epitopes of seven murine monoclonal antibodies have been identified by cryo-EM analysis of Fab-labeled capsids. All but one are conformational and all but one map around the spike tip. The exception, which is also the tightest-binder, straddles an inter-molecular interface on the floor. Seeking to relate these observations to the immunological response of infected humans, we isolated anti-cAg antibodies from a patient, prepared Fabs, and analyzed their binding to capsids.. A priori, one possibility was that many different Fabs would give an undifferentiated continuum of Fab-related density. In fact, the density observed was highly differentiated and could be reproduced by modeling with just five Fabs, three binding to the spike and two to the floor. These results show that epitopes on the floor, far (∼30. å) from the immunodominant loop, are clinically relevant and that murine anti-cAg antibodies afford a good model for the human system.

Original languageEnglish (US)
Pages (from-to)145-151
Number of pages7
JournalJournal of Structural Biology
Volume177
Issue number1
DOIs
StatePublished - Jan 2012
Externally publishedYes

Keywords

  • Antibody labeling
  • Conformational epitopes
  • Immunodominant epitopes
  • Molecular modeling
  • Polyclonal antibodies

ASJC Scopus subject areas

  • Structural Biology

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