The structures of secretory IgA in complex with human and bacterial Fc receptors and functional implications for mucosal host-pathogen interactions

Immunoglobulin (Ig) A serves a dual role as monomeric IgA in the serum and secretory (S) IgA in mucosal secretions. Host IgA Fc receptors (FcαRs), including human FcαR1/CD89, are responsible for mediating IgA's various effector functions. However, pathogens like Streptococcus pyogenes (Group A Streptococcus, GAS), have evolved surface proteins like M4 that can also engage the CD89 binding site on IgA. Despite human mucosa being a reservoir for pathogens, SIgA interactions with CD89 and M4 remain poorly understood. In this dissertation, I investigate the structural and functional aspects of these interactions. Using cryo-EM, I elucidated the structures of M4-SIgA and CD89-SIgA complexes, revealing differing SIgA-binding stoichiometry for M4 and CD89. Results suggest SIgA copies bound to GAS M4 adopt similar orientations on the bacterium's surface, leaving one host FcαR binding site open. Employing fluorescent labeling and confocal microscopy, I successfully visualized SIgA interactions on the GAS cell surface, laying the groundwork for future investigations into host-microbe interactions and bacterial immune evasion mechanisms. These findings highlight previously unrecognized functional consequences of SIgA binding to host and bacterial FcαRs, shedding light on host-microbe co-evolution and IgA's effector functions. In the dissertation's final chapter, I discuss the development of an innovative solid-state NMR pulse sequence for protein structure characterization. This method was successfully applied to a model protein GB1, demonstrating the robustness of this pulse sequence in protein structural determination.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biochemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2023

Author dc:creator

• Liu, Qianqiao

Contributors dc:contributor

• Stadtmueller, Beth
• Nair, Satish
• Huang, Raven
• Wu, Nicholas

• Iga
• Streptococcus Pyogene
• Mucosal Immunology
• Solid-state Nmr
• Structural Biology.

Statement dc:rights

• Copyright 2023 Qianqiao Liu

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/122205

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F122205