Using a Combined Computational-Experimental Approach to Predict Antibody-Specific B Cell Epitopes

• DOI: 10.1016/j.str.2014.02.003
• Publication Date: 2014-03-17T07:46:52Z
• Authors: Inbal Sela-Culang; Mohammed Rafii-El...; Michael H. Matho; Thomas Kaever; Matt Maybeno; Andrew Schlossman; Guy Nimrod; Sheng Li; Yan Xiang; Dirk Zajonc; Shane Crotty; Yanay Ofran; Bjoern Peters
• Keywords: Epitope mapping

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.