Exploring Humoral Immune Responses by Mass Spectrometry: Resolving Structures, Interactions, and Clonal Repertoires of Antibodies

Abstract

In his thesis “Exploring Humoral Immune Responses by Mass Spectrometry”, Maurits den Boer uses mass spectrometry to shed new light on antibody responses. Antibodies play a crucial role in the immune protection against threats like bacteria, viruses, and cancers. When valuable antibodies are discovered, they can therefore be reproduced for use as a medicine. A better understanding of their structures, interactions, and repertoires is therefore key to finding novel treatments for many diseases. In the first part of his thesis, Maurits and coworkers used mass spectrometry to study antibody structures and interactions, leading to two major findings. They first uncovered a mechanism by which Staphylococcus aureus bacteria can evade antibody responses, and how this mechanism may be circumvented in future therapies. Second, he redefined the textbook structure of circulating IgM antibodies by showing that they are universally attached to an extra protein. This may have major implications for how these antibodies function, and their use as therapeutics. In a second line of research, Maurits focused on the development of innovative techniques for antibody repertoire analysis and discovery. Together with coworkers, he explored the use of electron-based fragmentation mass spectrometry, developing methods to obtain valuable pieces of antibody sequence information. Finally, he combined multiple layers of mass spectrometry analysis to discover and fully determine the sequence of a malignant patient antibody. Combined, this demonstrates the promise of mass spectrometry as a compelling new approach for therapeutic antibody discovery.