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Structure. 2014 Apr 8;22(4):646-57. doi: 10.1016/j.str.2014.02.003. Epub 2014 Mar 13.

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

Author information

1
The Goodman Faculty of Life Sciences, Nanotechnology Building, Bar Ilan University, Ramat Gan 52900, Israel.
2
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
3
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
4
Medicine and Biomedical Sciences Graduate Program, University of California at San Diego, La Jolla, CA 92093, USA.
5
Department of Microbiology and Immunology, University of Texas Health Science Center, San Antonio, TX 78229, USA.
6
The Goodman Faculty of Life Sciences, Nanotechnology Building, Bar Ilan University, Ramat Gan 52900, Israel. Electronic address: yanay@ofranlab.org.
7
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. Electronic address: bpeters@liai.org.

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.

PMID:
24631463
DOI:
10.1016/j.str.2014.02.003
[Indexed for MEDLINE]
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