Using a combined computational-experimental approach to predict antibody-specific B cell epitopes

Inbal Sela-Culang, Mohammed Rafii El Idrissi Benhnia, Michael H. Matho, Thomas Kaever, Matt Maybeno, Andrew Schlossman, Guy Nimrod, Sheng Li, Yan Xiang, Dirk Zajonc, Shane Crotty, Yanay Ofran, Bjoern Peters

Research output: Contribution to journalArticle

30 Scopus citations


Antibody epitope mapping is crucial for understanding B cell-mediated immunity and required for characterizing therapeutic antibodies. In contrast to T cell epitope mapping, no computational tools are in widespread use for prediction of B cell epitopes. Here, we show that, utilizing the sequence of an antibody, it is possible to identify discontinuous epitopes on its cognate antigen. The predictions are based on residue-pairing preferences and other interface characteristics. We combined these antibody-specific predictions with results of cross-blocking experiments that identify groups of antibodies with overlapping epitopes to improve the predictions. We validate the high performance of this approach by mapping the epitopes of a set of antibodies against the previously uncharacterized D8 antigen, using complementary techniques to reduce method-specific biases (X-ray crystallography, peptide ELISA, deuterium exchange, and site-directed mutagenesis). These results suggest that antibody-specific computational predictions and simple cross-blocking experiments allow for accurate prediction of residues in conformational B cell epitopes.

Original languageEnglish (US)
Pages (from-to)646-657
Number of pages12
Issue number4
StatePublished - Apr 8 2014


ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Sela-Culang, I., Benhnia, M. R. E. I., Matho, M. H., Kaever, T., Maybeno, M., Schlossman, A., Nimrod, G., Li, S., Xiang, Y., Zajonc, D., Crotty, S., Ofran, Y., & Peters, B. (2014). Using a combined computational-experimental approach to predict antibody-specific B cell epitopes. Structure, 22(4), 646-657.