Structural analysis of B-cell epitopes in antibody: protein complexes
Open accessAbstract
The binding of antigens to antibodies is one of the key events in an immune response against foreign molecules and is a critical element of several biomedical applications including vaccines and immunotherapeutics. For development of such applications, the identification of antibody binding sites (B-cell epitopes) is essential. However experimental epitope mapping is highly cost-intensive and computer-aided methods do in general have moderate performance. One major reason for this moderate performance is an incomplete understanding of what characterizes an epitope. To fill this gap, we here developed a novel framework for comparing and superimposing B-cell epitopes and applied it on a dataset of 107 non-similar antigen:antibody structures extracted from the PDB database. With the presented framework, we were able to describe the general B-cell epitope as a flat, oblong, oval shaped volume consisting of predominantly hydrophobic amino acids in the center flanked by charged residues. The average epitope was found to be made up of ∼15 residues with one linear stretch of 5 or more residues constituting more than half of the epitope size. Furthermore, the epitope area is predominantly constrained to a plane above the antibody tip, in which the epitope is orientated in a -30° to 60° angle relative to the light to heavy chain antibody direction. Contrary to previously findings, we did not find a significant deviation between the amino acid composition in epitopes and the composition of equally exposed parts of the antigen surface. Our results, in combination with previously findings, give a detailed picture of the B-cell epitope that may be used in development of improved B-cell prediction methods.
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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 [168]
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- Authors
- Kringelum, J. V., Nielsen, M., Padkjær, S. B., & Lund, O.
- Affiliations
- Technical University of Denmark (DK)
- Novo Nordisk (Denmark) (DK)
- Corresponding author
- Lund, Ole
- Venue
- Molecular Immunology
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 53
- Issue
- 1-2
- Pages
- 24-34
- ISSN
- 0161-5890 (ISSN-L)
- PMC
- PMC3461403
- OpenAlex
- W2018470704
- Cited by
- 305
- References
- 47
- Citations by year
- 2026: 28 · 2025: 26 · 2024: 21 · 2023: 23 · 2022: 27 · 2021: 33 · 2020: 24 · 2019: 25 · 2018: 20 · 2017: 19 · 2016: 17 · 2015: 18 · 2014: 12 · 2013: 11 · 2012: 1
- FWCI
- 5.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Molecular Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (submittedVersion)
- Funders
- National Institutes of Health (HHSN26620040006C)
- 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 epitopes, antibody-antigen binding, epitope prediction, antibody binding sites
- MeSH terms
- Amino Acid Sequence, Antigen-Antibody Complex, Binding Sites, Antibody, Models, Molecular, Molecular Sequence Data, Epitope Mapping, Epitopes, B-Lymphocyte, Protein Structure, Quaternary
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