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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.
Afiliação
  • Sela-Culang I; The Goodman Faculty of Life Sciences, Nanotechnology Building, Bar Ilan University, Ramat Gan 52900, Israel.
  • Benhnia MR; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
  • Matho MH; Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
  • Kaever T; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
  • Maybeno M; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
  • Schlossman A; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
  • Nimrod G; The Goodman Faculty of Life Sciences, Nanotechnology Building, Bar Ilan University, Ramat Gan 52900, Israel.
  • Li S; Medicine and Biomedical Sciences Graduate Program, University of California at San Diego, La Jolla, CA 92093, USA.
  • Xiang Y; Department of Microbiology and Immunology, University of Texas Health Science Center, San Antonio, TX 78229, USA.
  • Zajonc D; Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
  • Crotty S; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
  • Ofran Y; The Goodman Faculty of Life Sciences, Nanotechnology Building, Bar Ilan University, Ramat Gan 52900, Israel. Electronic address: yanay@ofranlab.org.
  • Peters B; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. Electronic address: bpeters@liai.org.
Structure ; 22(4): 646-57, 2014 Apr 08.
Article em En | MEDLINE | ID: mdl-24631463
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peptídeos / Epitopos de Linfócito B / Anticorpos Monoclonais / Complexo Antígeno-Anticorpo / Antígenos Virais Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Revista: Structure Assunto da revista: BIOLOGIA MOLECULAR / BIOQUIMICA / BIOTECNOLOGIA Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Israel

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peptídeos / Epitopos de Linfócito B / Anticorpos Monoclonais / Complexo Antígeno-Anticorpo / Antígenos Virais Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Revista: Structure Assunto da revista: BIOLOGIA MOLECULAR / BIOQUIMICA / BIOTECNOLOGIA Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Israel