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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 646-657 |
| Number of pages | 12 |
| Journal | Structure |
| Volume | 22 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 8 2014 |
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ASJC Scopus subject areas
- Molecular Biology
- Structural Biology
- Medicine(all)
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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.
In: Structure, Vol. 22, No. 4, 08.04.2014, p. 646-657.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Using a combined computational-experimental approach to predict antibody-specific B cell epitopes
AU - Sela-Culang, Inbal
AU - Benhnia, Mohammed Rafii El Idrissi
AU - Matho, Michael H.
AU - Kaever, Thomas
AU - Maybeno, Matt
AU - Schlossman, Andrew
AU - Nimrod, Guy
AU - Li, Sheng
AU - Xiang, Yan
AU - Zajonc, Dirk
AU - Crotty, Shane
AU - Ofran, Yanay
AU - Peters, Bjoern
PY - 2014/4/8
Y1 - 2014/4/8
N2 - 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.
AB - 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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U2 - 10.1016/j.str.2014.02.003
DO - 10.1016/j.str.2014.02.003
M3 - Article
C2 - 24631463
AN - SCOPUS:84898492241
VL - 22
SP - 646
EP - 657
JO - Structure with Folding & design
JF - Structure with Folding & design
SN - 0969-2126
IS - 4
ER -