Allergies mediated by immunoglobulin E (IgE) encompass a wide range of conditions, including allergic asthma, food allergies, urticaria, and hypersensitivity to insect venom. Symptoms occur when allergens bind to IgE that is already bound to its high-affinity receptor (FceRI) on mast cells and basophils. Cross-linking and clustering of the IgE-FceRI complexes induced by allergens leads to cell activation and the release of inflammatory mediators that drive allergic reactions.

The severity of the allergic response can range from mild discomfort to life-threatening anaphylaxis. We have identified several binders that can modulate the IgE-mediated immune response via different mechanisms, such as preventing the formation of the IgE-FceRI complex, targeting the FceRI receptor or binding and sequestering the antigen to prevent cross-linking and clustering of the IgE-FceRI complexes. These binders exhibit diverse functional properties. Understanding their specific interactions with antigens, IgE, FceRI and the IgE-FceRI complex is fundamental to improving their efficacy and selectivity.

Such insights are essential for guiding the rational design of next-generation therapeutics for treating severe IgE-mediated allergies and preventing their life-threatening symptoms. However, obtaining high-resolution structural data remains time-consuming and is a bottleneck in therapeutic development. An efficient structural biology pipeline would accelerate therapeutic optimisation.