Antigen Geometry Tunes Mast Cell Signaling Through Distinct FcεRI Aggregation and Structural Changes.

This work elucidates the molecular mechanisms underlying differential FcεRI signaling responses induced by antigens of distinct geometries. By combining super-resolution imaging and biophysical techniques, we demonstrate that the physical attributes of allergens, including shape, flexibility, and valency, modulate mast cell signaling outcomes by altering FcεRI aggregate organization and conformational states. This provides novel insights into the structure-function relationships governing FcεRI signal transduction and its role in mast cell activation. Overall, this work establishes a link between allergen physical properties and immune receptor signaling at the molecular level, with important implications for understanding and regulating allergic responses.