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Harrington, W. N.

Publications and source records attributed to Harrington, W. N..

2 recordsLinked to original sources
bioRxiv2026

Structural evolution of Fcα/μR-mediated antibody recognition

The Fc alpha-mu receptor (Fc/R) is an ancient Fc-receptor sharing common ancestry with the polymeric Ig receptor (pIgR) and binding polymeric IgM and IgA ligands. In several vertebrate lineages, including birds, Fc/R may serve as the sole IgM and IgA Fc receptor; yet its evolution and ligand-recognition mechanisms across vertebrates remain poorly understood. Here, we identify FCAMR expression in duck (Anas platyrhynchos, ap) lymphoid tissues and demonstrate that recombinantly expressed apFc/R ectodomain binds apIgM and apIgA ligands. apFc/R affinity was ~10-fold higher for apIgM versus apIgA and ~10-fold higher than mouse (mm) Fc/R. Cryo-EM structures of apFc/R in complex with pentameric apIgM (3.27 [A]) and tetrameric apIgA (3.57 [A]) showed three Ig-like domains (D1-D3) bound asymmetrically with 1:1 stoichiometry. Comparisons to avian pIgR, which contains four Ig-like domains (D1-D4), revealed overlapping contacts between apFc/R-D1 and pIgR-D1. apFc/R D2-D3 engaged sites similar to pIgR D3-D4, yet formed distinct contact networks. Parallel analysis of a mmFc/R-mmIgM structure (4.13 [A]) revealed mmFc/R's single Ig-domain bound analogous to apFc/R-D1 and to mammalian pIgR-D1, whereas downstream ectodomain regions were not observed. Collectively, the data elucidate PIGR-family mechanisms across vertebrates, providing a foundation for delineating common and divergent functions.

immunology↗
bioRxiv2026

Structural insights into antibody responses against influenza A virus in its natural reservoir

While influenza A virus undergoes rapid antigenic drift in humans, at least some subtypes, such as H3, have relatively stable antigenicity in natural waterfowl reservoirs, despite the presence of immune pressure. However, the underlying mechanisms remain poorly understood. This study identified and characterized 187 antibodies to H3 hemagglutinin from experimentally infected mallard ducks, 18 of which were further analyzed by cryo-EM. Compared with human H3 antibodies, duck H3 antibodies exhibited higher glycan-binding propensity, more balanced immunodominance hierarchy, and targeted distinct epitopes. Other unique features of duck H3 antibodies included a convergent CDR H3-independent heavy chain-only binding mode and an N-glycosylated CDR H3 as decoy receptor. By annotating duck immunoglobulin germline genes, we also demonstrated the importance of gene conversion in duck H3 antibodies. Overall, our findings provide insights into how millennia of coevolution have shaped the interplay between influenza A virus antigenic drift and antibody responses in the natural reservoir.

immunology↗