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Humanized Mediator Release Assay as a Read-Out for Allergen Potency
Published on: June 29, 2021
Transient dimers of allergens.
Juha Rouvinen1, Janne Jänis, Marja-Leena Laukkanen
1Department of Chemistry, University of Eastern Finland, Joensuu, Finland. juha.rouvinen@uef.fi
Plos One
|February 9, 2010
Summary
Allergens often exist as dimers, enhancing their allergenicity by facilitating cross-linking of antibodies. Creating monomeric allergen variants may offer new avenues for allergy immunotherapy.
Area of Science:
- Immunology
- Structural Biology
- Biochemistry
Background:
- Type I allergy involves IgE antibody cross-linking on mast cells via FcepsilonRI receptors.
- Homodimeric allergens exhibit enhanced allergenicity due to simplified antibody binding for cross-linking.
Purpose of the Study:
- To investigate the prevalence and significance of allergen dimerization in allergic reactions.
- To explore the potential of monomeric allergen variants for therapeutic applications.
Main Methods:
- Analysis of 55 crystal structures of allergens to determine oligomeric states.
- Native mass spectrometry to assess allergen dimerization in solution.
- Creation and functional testing of a monomeric Bos d 5 allergen variant.
Main Results:
- 80% of analyzed allergens crystallize as dimers or oligomers.
- Allergens form transient dimers in solution at high concentrations, unlike hypoallergenic monomeric variants.
- A monomeric Bos d 5 variant demonstrated reduced histamine release.
Conclusions:
- Dimerization appears to be a common and crucial characteristic of allergens.
- Developing purely monomeric allergen forms presents a promising strategy for specific immunotherapy.
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