Epitope and Paratope Mapping Reveals Temperature-Dependent Alterations in the Dengue-Antibody Interface

Xin Xiang Lim, Arun Chandramohan, Xin Ying Elisa Lim, James E. Crowe, Shee Mei Lok, Ganesh S. Anand

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Uncovering mechanisms of antibody-mediated neutralization for viral infections requires epitope and paratope mapping in the context of whole viral particle interactions with the antibody in solution. In this study, we use amide hydrogen/deuterium exchange mass spectrometry to describe the interface of a dengue virus-neutralizing antibody, 2D22, with its target epitope. 2D22 binds specifically to DENV2, a serotype showing strain-specific structural expansion at human host physiological temperatures of 37°C. Our results identify the heavy chain of 2D22 to be the primary determinant for binding DENV2. Temperature-mediated expansion alters the mode of interaction of 2D22 binding. Importantly, 2D22 interferes with the viral expansion process and offers a basis for its neutralization mechanism. The relative magnitude of deuterium exchange protection upon antibody binding across the various epitope loci allows a deconstruction of the antibody-viral interface in host-specific environments and offers a robust approach for targeted antibody engineering.

Original languageEnglish (US)
Pages (from-to)1391-1402.e3
Issue number9
StatePublished - Sep 5 2017

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology


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