The structures, functions and therapeutic potential of secretory antibodies
by Beth Stadtmueller, PhD
Assistant Professor, Biochemistry and Biomedical & Translational Sciences
Carle Illinois College of Medicine
Innovation Grand Rounds
Friday, November 12, 2021
noon – 1:00 p.m. Presentation by Beth Stadtmueller
1:00 – 1:30 p.m. Reflection & Dialogue
Mucosal antibodies mediate host interactions with complex extracellular environments such as those found in the gut lumen. The predominant mucosal antibody in mammals is secretory (S) Immunoglobulin (Ig) A, which is a polymeric antibody that plays an important role in microbial homeostasis. Compared to monomeric antibodies, SIgA has unique molecular structure and unique capacities to bind receptors and to coat or cross-link mucosal antigens such as commensal and pathogenic bacteria. Despite significance, the molecular mechanisms underlying these interactions and their diverse functional outcomes remain poorly understood. This talk reports the Stadtmueller lab’s recently published cryo-electron microscopy structures of SIgA and its precursor. Structures reveal asymmetric complexes containing two IgAs that are bent and tilted with respect to each other, limiting the possible positions of antigen-binding fragments (Fabs) and preserving steric accessibility to receptor-binding sites. New structural insights inform models for how SIgA interacts with antigen and facilitates other effector functions while also providing a framework for engineering SIgA-based antibodies for therapeutic benefit.
Dr. Beth Stadtmueller is an Assistant Professor of Biochemistry and an Assistant Professor of Biomedical and Translational Sciences here at Illinois; she is also an affiliate member of the Beckman Institute. Beth was raised in Wisconsin and received a B.S. in Biochemistry from the University of Wisconsin-Madison. She completed a Ph.D. in Biochemistry at the University of Utah in the laboratory of Christopher Hill where she trained as a structural biologist and investigated the assembly and activation mechanisms of the proteasome. Subsequently, Beth joined Pamela Bjorkman’s laboratory at Caltech as a Cancer Research Institute-funded postdoctoral scholar; there, she published innovative and influential work revealing how host receptors interact with polymeric antibodies and how antibodies engage and neutralize HIV-1. Beth became an assistant professor at Illinois in November 2018. Her group investigates the structural and molecular basis for host immune system interactions with microbes with a focus on determining the structures, assembly mechanisms, functions and therapeutic potential of natural and engineered antibodies. Her research program is funded by the National Institute of Allergy and Infectious Disease.