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Journal Articles mAbs Year : 2021

Accurate determination of epitope for antibodies with unknown 3D structures

Yannick Corde
  • Function : Author
Zakaria Omahdi
  • Function : Author

Abstract

MAbTope is a docking-based method for the determination of epitopes. It has been used to successfully determine the epitopes of antibodies with known 3D structures. However, during the antibody discovery process, this structural information is rarely available. Although we already have evidence that homology models of antibodies could be used instead of their 3D structure, the choice of the template, the methodology for homology modeling and the resulting performance still have to be clarified. Here, we show that MAbTope has the same performance when working with homology models of the antibodies as compared to crystallographic structures. Moreover, we show that even low-quality models can be used. We applied MAbTope to determine the epitope of dupilumab, an anti-interleukin 4 receptor alpha subunit therapeutic antibody of unknown 3D structure, that we validated experimentally. Finally, we show how the MAbTope-determined epitopes for a series of antibodies targeting the same protein can be used to predict competitions, and demonstrate the accuracy with an experimentally validated example.
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Dates and versions

hal-03390655 , version 1 (21-10-2021)

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Shifa Tahir, Thomas Bourquard, Astrid Musnier, Yann Jullian, Yannick Corde, et al.. Accurate determination of epitope for antibodies with unknown 3D structures. mAbs, 2021, 13 (1), pp.1-10. ⟨10.1080/19420862.2021.1961349⟩. ⟨hal-03390655⟩
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