Research advances in hydrogen–deuterium exchange mass spectrometry for protein epitope mapping

With the development of biomedical technology, epitope mapping of proteins has become critical for developing and evaluating new protein drugs. The application of hydrogen–deuterium exchange for protein epitope mapping holds great potential. Although several reviews addressed the hydrogen–deuterium exchange, to date, only a few systematic reviews have focused on epitope mapping using this technology. Here, we introduce the basic principles, development history, and review research progress in hydrogen–deuterium exchange epitope mapping technology and discuss its advantages. We summarize the main hurdles in applying hydrogen–deuterium exchange epitope mapping technology, combined with relevant examples to provide specific solutions. We describe the epitope mapping of virus assemblies, disease-associated proteins, and polyclonal antibodies as examples of pattern introduction. Finally, we discuss the outlook of hydrogen–deuterium exchange epitope mapping technology. This review will help researchers studying protein epitopes to gain a more comprehensive understanding of this technology.