title: Using a combined computational-experimental approach to predict antibody-specific B cell epitopes.
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.
authors.affiliation: The Goodman Faculty of Life Sciences, Nanotechnology Building, Bar Ilan University, Ramat Gan 52900, Israel.
authors.forename: Inbal
authors.initials: I
authors.lastname: Sela-Culang
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
authors.forename: Mohammed Rafii-El-Idrissi
authors.initials: MR
authors.lastname: Benhnia
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Matho
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kaever
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
authors.forename: Matt
authors.initials: M
authors.lastname: Maybeno
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Schlossman
authors.affiliation: The Goodman Faculty of Life Sciences, Nanotechnology Building, Bar Ilan University, Ramat Gan 52900, Israel.
authors.forename: Guy
authors.initials: G
authors.lastname: Nimrod
authors.affiliation: Medicine and Biomedical Sciences Graduate Program, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Sheng
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Microbiology and Immunology, University of Texas Health Science Center, San Antonio, TX 78229, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
authors.forename: Dirk
authors.initials: D
authors.lastname: Zajonc
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
authors.forename: Shane
authors.initials: S
authors.lastname: Crotty
authors.affiliation: The Goodman Faculty of Life Sciences, Nanotechnology Building, Bar Ilan University, Ramat Gan 52900, Israel. Electronic address: yanay@ofranlab.org.
authors.forename: Yanay
authors.initials: Y
authors.lastname: Ofran
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. Electronic address: bpeters@liai.org.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Peters
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000737:chemistry* / Q000276:immunology; D000956:Antigens, Viral / Q000737:chemistry* / Q000276:immunology; D018360:Crystallography, X-Ray; D041961:Deuterium Exchange Measurement; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010455:Peptides / Q000737:chemistry* / Q000276:immunology; D014616:Vaccinia virus / Q000737:chemistry
chemical_list: D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000956:Antigens, Viral; D018985:Epitopes, B-Lymphocyte; D010455:Peptides