Birch pollen allergic patients have IgE and IgG antibodies binding to diverse patterns of conformational epitopes on the major allergen, Bet v 1
Schmalz S, Mayr V, Shosherova A, Gepp B, Ackerbauer D, Sturm G, Bohle B, Breiteneder H, Radauer C. Isotype-specific binding patterns of serum antibodies to multiple conformational epitopes of Bet v 1.
J Allergy Clin Immunol. 2021 Nov 2. doi: 10.1016/j.jaci.2021.10.026. Epub ahead of print. PMID: 34740603.
Birch pollen is one of the most important elicitors of respiratory allergy. More than 90% of birch pollen allergic patients develop IgE antibodies to the major allergen, Bet v 1. These antibodies also bind to Bet v 1-related allergens in plant foods and are responsible for most cases of birch pollen-associated plant food allergies. Data on the epitope recognition profiles of allergen-specific IgE and IgG may aid in elucidating the molecular basis of varying clinical outcomes of sensitization to Bet v 1 with respect to plant food allergy, for monitoring immunological changes during allergen immunotherapy (AIT) and for designing hypoallergenic Bet v 1 derivatives for safer and more effective types of AIT.
In this study, which was conducted by Stefanie Schmalz from Christian Radauer’s group and published in the Journal of Allergy and Clinical Immunology, we analyzed the epitope recognition profiles of Bet v 1-specific IgE, IgG1 and IgG4 in sera from birch pollen allergic patients. As Bet v 1-specific IgE binds to epitopes that depend on the native structure of the allergen, traditional epitope mapping methods measuring antibody binding to overlapping synthetic peptides could not be applied. Instead, we generated chimeric proteins that present individual potential conformational epitopes by grafting overlapping surface patches of Bet v 1 onto a non-IgE-binding bacterial homologue. By this, we produced 13 chimeric proteins that folded into native, Bet v 1-like structures. By probing these chimeras with patients’ sera, we showed that the epitope recognition profiles of Bet v 1-sensitized patients are polyclonal and highly individual and differ between Bet v 1-specific IgE, IgG1 and IgG4.
This work shows that epitope grafting to a non-allergenic homologue is an effective method that allows for mapping of conformational epitopes with large groups of sera from allergic patients. This approach may be applied to other respiratory allergens whose recognition by human IgE depends on their native conformations.
This work was supported by the Austrian Science Fund (FWF) grant P 30936-B30.