Structural Characterization of Mallard Secretory Immunoglobulin A Provides Insight On Host Response To Avian Influenza

Structurally diverse among vertebrates, secretory immunoglobulins (SIgs) are centrally involved in mucosal immune defenses against pathogens like avian influenza virus (AIV). Despite frequent exposure to AIV, aquatic birds, including ducks, rarely display severe symptoms, providing a reservoir that can promote zoonotic disease. Avian SIgs are poorly characterized and how they defend against AIV is not well understood. SIgA is the predominant mucosal antibody and in mammals consists of two IgA monomers held together by joining chain (JC) and bound by the polymeric Ig receptor’s ectodomain, secretory component (SC). Avian SIgA contains orthologous components with varied domain organization. We report evidence that avian IgA is predominantly tetrameric along with cryo-EM structures of IgA and SIgA at 3.76Å and 3.21Å resolution, respectively. Structures revealed unique geometric relationships between IgA subunits, suggesting each set of antigen binding fragments (Fabs) occupies a unique position relative to others. Comparative structure analysis revealed marked differences between mammalian and avian JC and SC, with N-terminal extensions in avian components stabilizing larger interfaces in SIgA compared to mammalian. Together, data suggest avian SIgA components co-evolved to promote tetrameric SIgA assembly, stability, and function that differ from mammals. Unique avian SIgA geometric and structural features likely influence antigen binding and associated effector functions. These features, along with the unique duck antibody repertoire, may translate to differences in influenza antigen engagement compared to mammals. These results are relevant to understanding how the duck mucosal immune response controls AIV, as well as investigating and mitigating zoonotic mechanisms.

Rebecca M. Schneider (1,2), Qianqiao Liu (1), Beth M. Stadtmueller (1,2,3,4) (1) Department of Biochemistry, University of Illinois, Urbana, Illinois, USA, (2) Carl R. Woese Institute for Genomic Biology, University of Illinois, Urbana, Illinois, USA, (3) Center for Biophysics and Quantitative Biology, University of Illinois, Urbana, Illinois, USA, (4) Department of Biomedical and Translational Sciences, Carle Illinois College of Medicine, University of Illinois, Urbana, Illinois, USA.

Transmission pathways, pathobiology, immune responses