Dataset Information

Determination of Crucial Immunogenic Epitopes in Major Peanut Allergy Protein, Ara h2, via Novel Nanoallergen Platform.

ABSTRACT: Current methods for detection and diagnosis of allergies do not provide epitope specific immunogenic information and hence lack critical information that could aid in the prediction of clinical responses. To address this issue, we developed a nanoparticle based platform, called nanoallergens that enable multivalent display of potential allergy epitopes for determining the immunogenicity of each IgE binding epitope. By synthesizing nanoallergens that present various epitopes from the major peanut allergen, Ara h2, we directly determined the immunogenicity of each epitope, alone and in combination with other epitopes, using patient sera. This information provided insights on which epitopes are most critical for physiological responses to Ara h2 and revealed the importance of both high and low affinity epitopes for allergic responses. We anticipate the nanoallergen platform to be used to provide information regarding allergic reactions and therefore potentially aid in more accurate diagnosis and design of personalized treatment options.

SUBMITTER: Deak PE

PROVIDER: S-EPMC5479826 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Determination of Crucial Immunogenic Epitopes in Major Peanut Allergy Protein, Ara h2, via Novel Nanoallergen Platform.

Deak Peter E PE Vrabel Maura R MR Kiziltepe Tanyel T Bilgicer Basar B

Scientific reports 20170621 1

Current methods for detection and diagnosis of allergies do not provide epitope specific immunogenic information and hence lack critical information that could aid in the prediction of clinical responses. To address this issue, we developed a nanoparticle based platform, called nanoallergens that enable multivalent display of potential allergy epitopes for determining the immunogenicity of each IgE binding epitope. By synthesizing nanoallergens that present various epitopes from the major peanut ...[more]

PMID: 28638052

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Project description:To address the urgent need for safe food allergen immunotherapy, we have developed a liver-targeting nanoparticle platform, capable of intervening in allergic inflammation, mast cell release and anaphylaxis through the generation of regulatory T-cells (Treg). In this communication, we demonstrate the use of a poly (lactide-co-glycolide acid) (PLGA) nanoparticle platform for intervening in peanut anaphylaxis through the encapsulation and delivery of a dominant protein allergen, Ara h 2 and representative T-cell epitopes, to liver sinusoidal endothelial cells (LSECs). These cells have the capacity to act as natural tolerogenic antigen-presenting cells (APC), capable of Treg generation by T-cell epitope presentation by histocompatibility (MHC) type II complexes on the LSEC surface. This allowed us to address the hypothesis that the tolerogenic nanoparticles platform could be used as an effective, safe, and scalable intervention for suppressing anaphylaxis to crude peanut allergen extract. Following the analysis of purified Ara h 2 and representative MHC-II epitopes Treg generation in vivo, a study was carried out to compare the best-performing Ara h 2 T-cell epitope with a purified Ara h 2 allergen, a crude peanut protein extract (CPPE) and a control peptide in an oral sensitization model. Prophylactic as well as post-sensitization administration of the dominant encapsulated Ara h 2 T-cell epitope was more effective than the purified Ara h2 in eliminating anaphylactic manifestations, hypothermia, and mast cell protease release in a frequently used peanut anaphylaxis model. This was accompanied by decreased peanut-specific IgE blood levels and increased TGF-β release in the abdominal cavity. The duration of the prophylactic effect was sustained for two months. These results demonstrate that targeted delivery of carefully selected T-cell epitopes to natural tolerogenic liver APC could serve as an effective platform for the treatment of peanut allergen anaphylaxis.

Project description:BackgroundThe peanut allergens Ara h 2, h 6, and h 7 are potent allergens and can trigger severe reactions. Ara h 7 consists of three isoforms differing in their ability to induce basophil degranulation, whereas the ability of Ara h 7.0201 is comparable to Ara h 2 and 6 as shown in previous literature.ObjectiveTo identify linear epitopes of Ara h 7.0101, Ara h 7.0201 and Ara h 7.0301 recognized by IgE and IgG4 from patients sensitized to Ara h 7 and to investigate their potential to elucidate divergent abilities of the Ara h 7 isoforms in inducing basophil activation.MethodsLinear epitopes recognized by IgE and IgG4 were mapped by peptide microarray analysis containing 15-mer peptides of Ara h 2.0201, 6, 7.0101, 7.0201 and 7.0301 and 39 peanut allergic patients sensitized to Ara h 7 (discovery). For validation, 20-mer peptides containing the minimal epitope and surrounding amino acids were incubated with 25 sensitized patients and 10 controls (validation).ResultsThree out of 14 linear epitopes were unique for each isoform (Ara h 7.0101: aa 97-109; Ara h 7.0201: aa 122-133; Ara h 7.0301: aa 65-74) but scarcely recognized by IgE. The main linear IgE epitope (aa 51-57) located in the long flexible loop of all Ara h 7 isoforms was bound by antibodies from 31% of the patients (discovery and validation cohort). Regarding IgG4, 55% of the patients recognized an epitope present on all isoforms (aa 55-65), whereas epitope aa 129-137, only present on Ara h 7.0101/0.0301, was recognized by 38% of the patients. Recognition was highly individual, although 20% of the patients recognized any linear epitope neither by IgE nor by IgG4 despite a low mean z-score of ≥ 1.7. Remarkably, only 50% of the patients recognized one or more epitopes by IgE.Conclusion & clinical relevanceAra h 7 isoforms share many linear epitopes being easily accessible for antibody binding. Unique epitopes, essential to elucidate divergent potencies, were scarcely recognized, suggesting a crucial involvement of conformational epitopes.

Dataset Information

Determination of Crucial Immunogenic Epitopes in Major Peanut Allergy Protein, Ara h2, via Novel Nanoallergen Platform.

Publications

Determination of Crucial Immunogenic Epitopes in Major Peanut Allergy Protein, Ara h2, via Novel Nanoallergen Platform.

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