Reviews and feature articleDeterminants of allergenicity
Section snippets
From T-cell response to IgE production and allergic disease
Type I reactions and symptoms can be explained by molecular-molecular interactions between the antigen and its corresponding IgE antibody. This aspect is situated at the end of a cascade of events leading to allergy. A precondition for this cascade to start is specific recognition of the allergen on antigen-presenting cells, which, in the case of T-cell responses, is accomplished by the antigen-specific T-cell receptor (TCR). However, the TCR-transmitted signal alone is insufficient to induce
Allergen source and individual exposure
The most important sources of allergens are wind-dispersed pollen grains from trees, grasses, and weeds, followed by excretions of house dust mites and cockroaches, fungal spores, and animal dander and insect venoms.
The route of exposure, dose, and function of the allergen are crucial to mount an allergic sensitization. Sensitization occurs at the site of allergen exposure, such as the airways and skin, but can also occur through the gastrointestinal tract. In general terms, exposure to low
Molecular features of allergens
The allergens that elicit type I allergies are mostly proteins or glycoproteins and cluster in less than 2% of all (9318) known protein families (AllFam database: www.meduniwien.ac.at/allergens/allfam).58, 59 This would seem to imply that structural and biochemical similarities between allergenic proteins and the comparison of allergenic and nonallergenic members of the same protein family could explain what determines allergenicity. The primary structure (amino acid sequence) of a protein
Intrinsic function of allergens
A large number of allergens have intrinsic biologic functions. They act as proteases, pectate lyases, trypsin inhibitors, calcium-binding proteins, lipid transfer proteins, actin-binding proteins, and others. Some of these biologic activities can contribute to allergenicity by increasing the tissue distribution of the allergen through digestion of extracellular matrix (eg, hyaluronidase), degradation of cellular adhesion molecules (eg, house dust mite major allergen Der p 1 or the Penicillium
Biogenic cofactors contributing to allergenicity
Allergen research has mainly focused on identifying single allergens and characterizing their biochemical, structural, and functional properties. Little attention has been paid to the natural context under which these allergens are encountered by the organism. Except for testing in clinical settings, individuals will never be exposed to isolated allergens but are usually exposed to their carriers. This implies that other factors being liberated from the allergen carrier or exposed together with
Environmental pollutants as contributing factors
The same holds true for environmental pollutants, which can facilitate the development of type I allergies through several different mechanisms. The best-studied particulate pollutants are diesel exhaust particles (DEPs), which were shown to turn a harmless neoantigen into an allergen capable of inducing high levels of allergen-specific IgE.44, 113 Susceptibility genes for the adjuvant effect of DEPs have been identified (eg, glutathione-S-transferase and Nrf2) and suggest that DEP-induced
Summary and future perspectives
Rapid progress in molecular and clinical allergy research has advanced our understanding of the structural and functional nature of allergens and has led to improved classifications according to taxonomy and protein families. This knowledge has resulted in better characterization and standardization of allergen extracts, the design of novel hypoallergenic mutants for safer allergen-specific immunotherapy, and the development of novel strategies for advanced diagnostics and patient-tailored
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Disclosure of potential conflict of interest: T. Jakob receives grant support from the German Ministry of Research and Science, the University of Freiburg Medical Faculty, and the Landesstifung Baden Wuettemberg and is a member of the Executive Committee for the European Academy of Allergy and Clinical Immunology and a board member for the European Immunodermatology Society. The rest of the authors have declared that they have no conflict of interest.
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These authors contributed equally to this work.