A native IgE in complex with profilin provides insights into allergen recognition and cross-reactivity

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 angstrom(2), 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. The crystal structures of the murine IgE antibody in complex with highly cross-reactive profilins are reported, and the data of cross-reactivity among allergen mutants with antibodies may prove helpful for research applications in allergy therapeutics.

Automated summary

Allergies have become a growing health problem, and allergens play a major role in triggering allergic reactions. This study reports the crystal structures of murine IgE antibody in complex with an allergen, revealing specific interactions and high affinity between the antibody and allergen. Additionally, experiments with allergen mutants suggest that this antibody may be a promising tool for allergy diagnosis and research applications.