Allergens and their associated small molecule ligands - their dual role in sensitization

Authors: CHRUSZCZ, MAKSYMILIAN - University Of South Carolina; CHEW, FOOK TIM - National University Of Singapore; SOMMERGRUBER, KARIN - Medical University Of Veinna; Hurlburt, Barry; MUELLER, GEOFFREY - Nih, National Institutes Of Allergy And Infectious Diseases; POMES, ANNA - Indoor Biotechnologies; ROUVINEN, JUHA - University Of Eastern Finland; VILLALBA, MAYTE - Complutense University Of Madrid (UCM); WOHRL, BIRGITTA - University Of Bayreuth; BREITENEDER, HEIMO - Medical University Of Veinna

Submitted to: Allergy
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/10/2021
Publication Date: 5/2/2021
Citation: Chruszcz, M., Chew, F.T., Hoffmann-Sommergruber, K., Hurlburt, B.K., Mueller, G.A., Pomes, A., Rouvinen, J., Villalba, M., Wohrl, B.M., Breiteneder, H. 2021. Allergens and their associated small molecule ligands - their dual role in sensitization. Allergy. 76:2367-2382. https://doi.org/10.1111/all.14861.
DOI: https://doi.org/10.1111/all.14861

Interpretive Summary: Allergens are usually proteins. This is a review of the allergens that can bind small molecules and the effects that binding has on allergenicity.

Technical Abstract: A substantial number of allergens feature hydrophobic cavities that allow the binding of mostly hydrophobic small molecule ligands. The ligand-binding specificities can be strict or promiscuous. Examples include serum albumins, which originate from mammals and birds, and can assume multiple conformations that facilitate the binding of a broad spectrum of compounds. Pollen and plant food allergens from the family 10 of pathogenesis-related proteins have been shown in vitro to bind a variety of small molecules such as glycosylated flavonoid derivatives, flavonoids, cytokinins, and steroids. H owever, their natural ligand-binding was reported to behighly specific, in contrast to allergenic serum albumin. Insect and mammalian lipocalins transport odorants, pheromones, catecholamines, and fatty acids with a similar level of specificity, while the food allergen lactoglobulin from cow’s milk is notably more promiscuous. Finally, non-specific lipid transfer proteins from pollen and plant foods bind a wide variety of lipids, from phospholipids to fatty acids, as well as sterols and prostaglandin B2,aided by the high plasticity and flexibility displayed by their lipid-binding cavities. In summary,ligand-binding allergens expose the immune system to a variety of biologically active compounds whose impact on the sensitization process has not been well studied thus far.