Dataset Information

Determination of immunogenic epitopes in major house dust mite allergen, Der p 2, via nanoallergens.

ABSTRACT:

Background

Despite the high prevalence of allergic asthma, currently, avoidance of the responsible allergens, which is nearly impossible for allergens such as house dust mite (HDM), remains among the most effective treatment. Consequently, determination of the immunogenic epitopes of allergens will aid in developing a better understanding of the condition for diagnostic and therapeutic purposes. Current methods of epitope identification, however, only evaluate immunoglobulin E-epitope binding interactions, which is not directly related to epitope immunogenicity.

Objective

To determine and rank the immunogenicity of the epitopes of major HDM allergen, Der p 2.

Methods

We performed degranulation assays with RBL-SX38 cells primed using patient plasma and challenged with nanoallergens which multivalently displayed epitopes to study the relative immunogenicity of various epitopes of Der p 2. Nanoallergens were used to evaluate epitopes individually or in combination.

Results

When evaluated using 3 patient samples, 3 epitopes in 2 distal regions of Der p 2 were identified as highly immunogenic when presented in combination, whereas no individual epitope triggered relevant degranulation. One of the epitopes (69-DPNACHYMKCPLVKGQQY-86) was identified to be cooperatively immunogenic when combined with other epitopes.

Conclusion

Our study highlights the importance of conformational epitopes in HDM-related allergies. This study also provides further evidence of the versatility of nanoallergens and their value for functional characterization of allergy epitopes, by ranking the Der p 2 epitopes according to immunogenicity. We believe that nanoallergens, by aiding in identification and understanding of immunogenic epitopes, will provide a better understanding of the manifestation of the allergic condition and potentially aid in developing new treatments.

SUBMITTER: Sjoerdsma J

PROVIDER: S-EPMC9808607 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Determination of immunogenic epitopes in major house dust mite allergen, Der p 2, via nanoallergens.

Sjoerdsma Jenna J Mejia Franklin F Bilgicer Basar B

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 20220409 2

<h4>Background</h4>Despite the high prevalence of allergic asthma, currently, avoidance of the responsible allergens, which is nearly impossible for allergens such as house dust mite (HDM), remains among the most effective treatment. Consequently, determination of the immunogenic epitopes of allergens will aid in developing a better understanding of the condition for diagnostic and therapeutic purposes. Current methods of epitope identification, however, only evaluate immunoglobulin E-epitope bi ...[more]

PMID: 35405356

Similar Datasets

Project description:PurposeHypoallergenic recombinant Der p 2 has been produced by various genetic manipulations, but mutation of a naturally polymorphic amino acid residue known to affect IgE binding has not been studied. This study aimed to determine the effect of a point mutation (S47W) of residue 47 of Der p 2 on its structure and immunoglobulin (Ig) E binding. Its ability to induce pro-inflammatory responses and to induce blocking IgG antibody was also determined.MethodsS47 of recombinant Der p 2.0110, one of the predominant variants in Bangkok, was mutated to W (S47W). S47W secreted from Pichia pastoris was examined for secondary structure and for the formation of a hydrophobic cavity by 8-Anilino-1-naphthalenesulfonic acid (ANS) staining. Monoclonal and human IgE-antibody binding was determined by enzyme-linked immunosorbent assay. Allergen-induced degranulation by human epsilon receptor expressed-rat basophil was determined. Stimulation of the pro-inflammatory cytokine interleukin (IL)-8 release from human bronchial epithelial (BEAS2B) cells and inhibition of IgE binding to the wild type allergen by S47W-induced IgG were determined.ResultsS47W reduced secondary structure and failed to bind the hydrophobic ANS ligand as well as a monoclonal antibody known to be dependent on the nature of the side chain of residue 114 in an adjacent loop. It could also not stimulate IL-8 release from BEAS2B cells. IgE from house dust mite (HDM)-allergic Thais bound S47W with 100-fold weaker avidity, whereas IgE of HDM-allergic Australians did not. S47W still induced basophil degranulation, although requiring higher concentrations for some subjects. Anti-S47W antiserum-immunized mice blocked the binding of human IgE to wild type Der p 2.ConclusionsThe mutant S47W had altered structure and reduced ability to stimulate pro-inflammatory responses and to bind IgE, but retained its ability to induce blocking antibodies. It thus represents a hypoallergen produced by a single mutation of a non-solvent-accessible amino acid.

Dataset Information

Determination of immunogenic epitopes in major house dust mite allergen, Der p 2, via nanoallergens.

Background

Objective

Methods

Results

Conclusion

Publications

Determination of immunogenic epitopes in major house dust mite allergen, Der p 2, via nanoallergens.

Similar Datasets

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