Current progress in the understanding of IgE-FcepsilonRI interaction.

The last decade has seen a wealth of studies aimed at the characterization of the binding between IgE and its high-affinity receptor, FcepsilonRI. IgE-FcepsilonRI complex formation is a major molecular event in atopic allergy. IgE-FcepsilonRI binding connects allergen recognition to cellular triggering, ultimately leading to disease manifestations. Consequently, pharmacological intervention at this site is of universal relevance for atopic allergy. Until recent years, the complexity of IgE-FcepsilonRI binding, together with the difficulty in obtaining fully functional recombinant IgE and FcepsilonRI derivatives, often led to confusion and difficulty in data interpretation. Major advances in the understanding of this intricate protein-protein interaction have now been accomplished. Most of the current knowledge on the IgE-FcepsilonRI recognition mode derives from long-lasting efforts in the field of structural biology. Protein engineering, high-throughput screening, immunological and biochemical studies also made relevant contributions in this domain. The data accumulated to date predict that IgE and FcepsilonRI use their modular architecture to approach each other in an asymmetric stepwise manner determining a 1:1 stoichiometry. This recognition appears to be enhanced by conformational changes occurring upon binding, leading to the well-known high-affinity. In conclusion, the vast amount of high-quality data available broadened our knowledge on the IgE-FcepsilonRI system; however, the fine structural details of the recognition process are still largely hypothetical. More studies are necessary to provide the experimental comprehensive picture required to carefully design efficient drugs acting at the IgE-FcepsilonRI interface.