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

27 Citations (Scopus)

Abstract

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
JournalStructure
Volume22
Issue number4
DOIs
StatePublished - Apr 8 2014

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B-Lymphocyte Epitopes
Antibodies
Epitope Mapping
Epitopes
Antigens
T-Lymphocyte Epitopes
Deuterium
X Ray Crystallography
Site-Directed Mutagenesis
Cellular Immunity
B-Lymphocytes
Enzyme-Linked Immunosorbent Assay
Peptides

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology
  • Medicine(all)

Cite this

Sela-Culang, I., Benhnia, M. R. E. I., Matho, M. H., Kaever, T., Maybeno, M., Schlossman, A., ... Peters, B. (2014). Using a combined computational-experimental approach to predict antibody-specific B cell epitopes. Structure, 22(4), 646-657. https://doi.org/10.1016/j.str.2014.02.003

Using a combined computational-experimental approach to predict antibody-specific B cell epitopes. / Sela-Culang, Inbal; Benhnia, Mohammed Rafii El Idrissi; Matho, Michael H.; Kaever, Thomas; Maybeno, Matt; Schlossman, Andrew; Nimrod, Guy; Li, Sheng; Xiang, Yan; Zajonc, Dirk; Crotty, Shane; Ofran, Yanay; Peters, Bjoern.

In: Structure, Vol. 22, No. 4, 08.04.2014, p. 646-657.

Research output: Contribution to journalArticle

Sela-Culang, I, Benhnia, MREI, Matho, MH, 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, vol. 22, no. 4, pp. 646-657. https://doi.org/10.1016/j.str.2014.02.003
Sela-Culang I, Benhnia MREI, Matho MH, Kaever T, Maybeno M, Schlossman A et al. Using a combined computational-experimental approach to predict antibody-specific B cell epitopes. Structure. 2014 Apr 8;22(4):646-657. https://doi.org/10.1016/j.str.2014.02.003
Sela-Culang, Inbal ; Benhnia, Mohammed Rafii El Idrissi ; Matho, Michael H. ; Kaever, Thomas ; Maybeno, Matt ; Schlossman, Andrew ; Nimrod, Guy ; Li, Sheng ; Xiang, Yan ; Zajonc, Dirk ; Crotty, Shane ; Ofran, Yanay ; Peters, Bjoern. / Using a combined computational-experimental approach to predict antibody-specific B cell epitopes. In: Structure. 2014 ; Vol. 22, No. 4. pp. 646-657.
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