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

doi:10.1016/j.str.2014.02.003

Cited by 69vaccines and immunoinformatics approachesMonoclonal and Polyclonal Antibodies ResearchProtein Structure and Dynamics

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

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Sela-Culang, Inbal, Benhnia, Mohammed Rafii-El-Idrissi, Matho, Michael H., Kaever, Thomas, Maybeno, Matt, Schlossman, Andrew, Nimrod, Guy, Li, Sheng +5 more·2014·Structure

DOI 10.1016/j.str.2014.02.003

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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.

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Arbitrary molecular surfaces appear to be indistinguishable from epitope regions, suggesting that predictions should be performed with reference to a particular antibody.
“However, arbitrary molecular surfaces appear to be indistinguishable from epitope regions [167–169] suggesting that predictions should be performed with reference to a particular antibody [116, 118–120].”
From Computational approaches to therapeutic antibody design: established methods and emerging trends (2020) · cites this paper as [118]

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Structural bioinformatics Advance Access publication April 21, 2014 Improving B-cell epitope prediction and its application to global antibody-antigen docking
Krawczyk, K., Liu, X., Baker, T., Shi, J., Deane, C. M., & Tramontano, A. (2016)

Authors: 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.
Affiliations: La Jolla Institute for Immunology (US)
Bar-Ilan University (IL)
University of California San Diego (US)
The University of Texas at San Antonio Health Science Center (US)
Corresponding author: Ofran, Yanay
Peters, Bjoern
ORCID: Benhnia, Mohammed Rafii-El-Idrissi
Kaever, Thomas
Nimrod, Guy
Li, Sheng
Xiang, Yan
Zajonc, Dirk
Crotty, Shane
Peters, Bjoern
Venue: Structure
Publisher: Elsevier BV
Published: 2014-04
Volume: 22
Issue: 4
Pages: 646-657
ISSN: 0969-2126 (ISSN-L)
DOI: 10.1016/j.str.2014.02.003
OpenAlex: W2092240438
Cited by: 69
References: 67
Citations by year: 2026: 2 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 12 · 2021: 7 · 2020: 5 · 2019: 6 · 2018: 6 · 2017: 7 · 2016: 4 · 2015: 6 · 2014: 5
FWCI: 3.01
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 372 d)
Locations: Structure (publishedVersion)
PubMed (publishedVersion)
Funders: Israel Science Foundation
U.S. Public Health Service (HHSN272200900048C)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords: B-cell epitope prediction, epitope mapping, conformational epitopes, antibody-antigen interface, therapeutic antibodies, hydrogen-deuterium exchange
MeSH terms: Amino Acid Sequence, Animals, Antibodies, Monoclonal, Antigen-Antibody Complex, Antigens, Viral, Enzyme-Linked Immunosorbent Assay, Humans, Models, Molecular, Molecular Sequence Data, Peptides, Vaccinia virus, Mutagenesis, Site-Directed, Crystallography, X-Ray, Epitope Mapping, Epitopes, B-Lymphocyte, Deuterium Exchange Measurement, Mice

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

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