Title
A native IgE in complex with profilin provides insights into allergen recognition and cross-reactivity
Author
Benjamín García-Ramírez, Israel Mares-Mejía, Annia Rodríguez-Hernández, Patricia Cano-Sánchez, Alfredo Torres-Larios, Enrique Ortega & Adela Rodríguez-Romero
Year
2022
Journal
Communications Biology
Abstract
Allergies have become a rising health problem, where plentiful substances can trigger IgE-mediated allergies in humans. While profilins are considered minor allergens, these ubiquitous proteins are primary molecules involved in cross-reactivity and pollen-food allergy syndrome. Here we report the first crystal structures of murine Fab/IgE, with its chains naturally paired, in complex with the allergen profilin from Hevea brasiliensis (Hev b 8). The crystallographic models revealed that the IgE’s six complementarity-determining regions (CDRs) interact with the allergen, comprising a rigid paratope-epitope surface of 926 Å2, which includes an extensive network of interactions. Interestingly, we also observed previously unreported flexibility at Fab/IgE’s elbow angle, which did not influence the shape of the paratope. The Fab/IgE exhibits a high affinity for Hev b 8, even when using 1 M NaCl in BLI experiments. Finally, based on the encouraging cross-reactivity assays using two mutants of the maize profilin (Zea m 12), this antibody could be a promising tool in IgE engineering for diagnosis and research applications.
Full Article
Instrument
J-1500
Keywords
Allergies, IgE, crystal structure, CDRs