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Review
. 2023 Sep;23(9):497-508.
doi: 10.1007/s11882-023-01100-2. Epub 2023 Jun 23.

Role of Small Molecule Ligands in IgE-Mediated Allergy

Kriti Khatri  1   2 , Andrea O'Malley  1   2 , Christina Linn  1 , Krzysztof Kowal  3 , Maksymilian Chruszcz  4
Affiliations
Review

Role of Small Molecule Ligands in IgE-Mediated Allergy

Kriti Khatri et al. Curr Allergy Asthma Rep. 2023 Sep.

Abstract

Purpose of review: A significant fraction of allergens bind small molecular ligands, and many of these compounds are classified as lipids. However, in most cases, we do not know the role that is played by the ligands in the allergic sensitization or allergic effector phases.

Recent findings: More effort is dedicated toward identification of allergens' ligands. This resulted in identification of some lipidic compounds that can play active immunomodulatory roles or impact allergens' molecular and allergic properties. Four allergen families (lipocalins, NPC2, nsLTP, and PR-10) are among the best characterized in terms of their ligand-binding properties. Allergens from these four families are able to bind many chemically diverse molecules. These molecules can directly interact with human immune system and/or affect conformation and stability of allergens. While there is more data on the allergens and their small molecular ligands, we are just starting to understand their role in allergy.

Keywords: Allergens; Allergy; Lipocalins; NPC2; PR-10; nsLTP.

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Conflict of interest statement

Conflict of Interest Dr. Kowal reports personal fees from ALK Abello, personal fees from Astra Zeneca, personal fees from Aurovitas Pharma Polska, personal fees from Berlin Chemie, personal fees from Boehringer Ingelheim, personal fees from EMMA MDT, personal fees from HAL Allergy, personal fees from Stallergenes, outside of the submitted work. Other declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Representative structures of allergens form lipocalin and NPC2 protein families. a Bos d 5 (lipocalin) in complex with retinoic acid (PDB code: 1GX9). b Der p 2 with a non-physiological ligand (polyethylene glycol) that mimics a natural ligand (PDB code: 1XWV). Proteins are shown in ribbon representation with β-strands colored in teal, helices in red, and loop regions in grey. The ligands are shown using a space-filling representation.
Fig. 2
Fig. 2
Representative structures of allergens from nsLTP and PR-10 families. a Tri a 14 in complex with two molecules of a phospholipid (PDB code: 1BWO). b Ara h 8 in complex with three molecules of quercetin (PDB code: 6AWS). Proteins are shown in ribbon representation with β-strands colored in teal, helices in red, and loop regions in grey. The ligands are shown using a space-filling representation.
Fig. 3
Fig. 3
Experimentally confirmed interactions between allergens and small molecular compounds. a nsLTP allergen family, and b PR-10 (Bet v 1-like) family.
See this image and copyright information in PMC

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