Complementary roles for lipid and protein allergens in triggering innate and adaptive immune systems

Background:  Recent advances in allergy research mostly focussed on two major headings: improving protein allergen purification, which is aimed towards a better characterization of IgE‐ and T‐cell reactive epitopes, and the potential new role for unconventional innate and regulatory T cells in controlling airway inflammation. These advancements could appear to be in conflict each other, as innate T cells have a poorly‐defined antigen specificity that is often directed toward nonprotein substances, such as lipids. Method:  To reconcile these contrasting findings, the model of cypress pollinosis as paradigmatic for studying allergic diseases in adults is suggested. Results:  The biochemical characterization of major native protein allergens from undenatured pollen grain demonstrated that the most relevant substance with IgE‐binding activity is a glycohydrolase enzyme, which easily denaturizes in stored grains. Moreover, lipids from the pollen membrane are implicated in early pollen grain capture and recognition by CD1 + dendritic cells (DC) and CD1‐restricted T lymphocytes. These T cells display Th0/Th2 functional activity and are also able to produce regulatory cytokines, such as IL‐10 and TGF‐β. CD1 + immature DCs expand in the respiratory mucosa of allergic subjects and are able to process both proteins and lipids. Conclusion:  A final scenario may suggest that expansion and functional activation of CD1 + DCs is a key step for mounting a Th0/Th2‐deviated immune response, and that such innate response does not confer long‐lasting protective immunity.