Ara h 2 peptides containing dominant CD4+ T-cell epitopes: Candidates for a peanut allergy therapeutic

Prickett, Sara; Voskamp, Astrid; Dacumos-Hill, April; Symons, Karen; Rolland, Jennifer M.; O’Hehir, Robyn E

doi:10.1016/j.jaci.2010.09.027

Cited by 84 publications

(100 citation statements)

References 62 publications

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“…T-cell epitope peptides from major allergens could provide effective and safer (non-IgE-reactive) alternatives for the conventional immunotherapy treatment [44]. Five dominant CD4+ T-cell epitopes of Ara h 2 peptides have been identified as novel candidates for T-cell-targeted peanut allergy therapeutics [47].…”

Section: Discussionmentioning

confidence: 99%

In Silico Identification and in Vitro Analysis of B and T-Cell Epitopes of the Black Turtle Bean (Phaseolus Vulgaris L.) Lectin

Zhao

Elfalleh

et al. 2018

Cell Physiol Biochem

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Background/Aims: The incidence of lectin allergic disease is increasing in recent decades, and definitive treatment is still lacking. Identification of B and T-cell epitopes of allergen will be useful in understanding the allergen antibody responses as well as aiding in the development of new diagnostics and therapy regimens for lectin poisoning. In the current study, we mainly addressed these questions. Methods: Three-dimensional structure of the lectin from black turtle bean (Phaseolus vulgaris L.) was modeled using the structural template of Phytohemagglutinin from P. vulgaris (PHA-E, PDB ID: 3wcs.1.A) with high identity. The B and T-cell epitopes were screened and identified by immunoinformatics and subsequently validated by ELISA, lymphocyte proliferation and cytokine profile analyses. Results: Seven potential B-cell epitopes (B1 to B7) were identified by sequence and structure based methods, while three T-cell epitopes (T1 to T3) were identified by the predictions of binding score and inhibitory concentration. The epitope peptides were synthesized. Significant IgE binding capability was found in B-cell epitopes (B2, B5, B6 and B7) and T2 (a cryptic B-cell epitope). T1 and T2 induced significant lymphoproliferation, and the release of IL-4 and IL-5 cytokine confirmed the validity of T-cell epitope prediction. Abundant hydrophobic amino acids were found in B-cell epitope and T-cell epitope regions by amino acid analysis. Positively charged amino acids, such as His residue, might be more favored for B-cell epitope. Conclusion: The present approach can be applied for the identification of epitopes in novel allergen proteins and thus for designing diagnostics and therapies in lectin allergy.

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Section: Discussionmentioning

confidence: 99%

In Silico Identification and in Vitro Analysis of B and T-Cell Epitopes of the Black Turtle Bean (Phaseolus Vulgaris L.) Lectin

Zhao

Elfalleh

et al. 2018

Cell Physiol Biochem

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“…Peptides derived from enzymatically hydrolyzed flours selected for OIT should ideally contain the epitopes targeting CD4+ T cells, but lack the capacity to cross-link IgE on mast cells and basophils. For example, the potential for Ara h 2 peptides to be used in OIT was investigated in model systems [12]. The researchers identified short Ara h 2 peptides containing T cell epitopes that target Ara h 2-specific CD4+ T cells but lack the capacity to bind IgE, which suggest these peptides are good immunotherapy candidates [12].…”

Section: Introductionmentioning

confidence: 99%

“…For example, the potential for Ara h 2 peptides to be used in OIT was investigated in model systems [12]. The researchers identified short Ara h 2 peptides containing T cell epitopes that target Ara h 2-specific CD4+ T cells but lack the capacity to bind IgE, which suggest these peptides are good immunotherapy candidates [12]. Before enzymatically hydrolyzed flours can be considered for OIT, additional basic characterization data is needed.…”

Section: Introductionmentioning

confidence: 99%

Allergenic Properties of Enzymatically Hydrolyzed Peanut Flour Extracts

Shi

Guo

White

et al. 2013

Int Arch Allergy Immunol

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Background: Peanut flour is a high-protein, low-oil, powdered material prepared from roasted peanut seed. In addition to being a well-established food ingredient, peanut flour is also the active ingredient in peanut oral immunotherapy trials. Enzymatic hydrolysis was evaluated as a processing strategy to generate hydrolysates from peanut flour with reduced allergenicity. Methods: Soluble fractions of 10% (w/v) light roasted peanut flour dispersions were hydrolyzed with the following proteases: Alcalase (pH 8.0, 60°C), pepsin (pH 2.0, 37°C) or Flavourzyme (pH 7.0, 50°C) for 60 min. Western blotting, inhibition ELISA and basophil activation tests were used to examine IgE reactivity. Results: Western blotting experiments revealed the hydrolysates retained IgE binding reactivity and these IgE-reactive peptides were primarily Ara h 2 fragments regardless of the protease tested. Inhibition ELISA assays demonstrated that each of the hydrolysates had decreased capacity to bind peanut-specific IgE compared with nonhydrolyzed controls. Basophil activation tests revealed that all hydrolysates were comparable (p > 0.05) to nonhydrolyzed controls in IgE cross-linking capacity. Conclusions: These results indicate that hydrolysis of peanut flour reduced IgE binding capacity; however, IgE cross-linking capacity during hydrolysis was retained, thus suggesting such hydrolysates are not hypoallergenic.

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“…Nitrocellulose membrane (0.2 µm pore size) was dotted with 10 µg of Pas n 1 protein or 20 µg of Pas n 1 peptide, blocked with TRIS-buffered saline containing 0.05% Tween 20 and 5% sucrose, incubated with individual subject sera (diluted 1:10) and IgE binding was assessed as described [24]. …”

Section: Methodsmentioning

confidence: 99%

Unique and Cross-Reactive T Cell Epitope Peptides of the Major Bahia Grass Pollen Allergen, Pas n 1

Etto

Boer

Prickett

et al. 2012

Int Arch Allergy Immunol

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Background: Bahia grass pollen (BaGP) is a major cause of allergic rhinitis. Subcutaneous allergen-specific immunotherapy is effective for grass pollen allergy, but is unsuitable for patients with moderate to severe asthma due to the risk of anaphylaxis. T cell-reactive but IgE nonreactive peptides provide a safer treatment option. This study aimed to identify and characterize dominant CD4⁺ T cell epitope peptides of the major BaGP allergen, Pas n 1. Methods: Pas n 1-specific T cell lines generated from the peripheral blood of BaGP-allergic subjects were tested for proliferative and cytokine response to overlapping 20-mer Pas n 1 peptides. Cross-reactivity to homologous peptides from Lol p 1 and Cyn d 1 of Ryegrass and Bermuda grass pollen, respectively, was assessed using Pas n 1 peptide-specific T cell clones. MHC class II restriction of Pas n 1 peptide T cell recognition was determined by HLA blocking assays and peptide IgE reactivity tested by dot blotting. Results: Three Pas n 1 peptides showed dominant T cell reactivity; 15 of 18 (83%) patients responded to one or more of these peptides. T cell clones specific for dominant Pas n 1 peptides showed evidence of species-specific T cell reactivity as well as cross-reactivity with other group 1 grass pollen allergens. The dominant Pas n 1 T cell epitope peptides showed HLA binding diversity and were non-IgE reactive. Conclusions: The immunodominant T cell-reactive Pas n 1 peptides are candidates for safe immunotherapy for individuals, including those with asthma, who are allergic to Bahia and possibly other grass pollens.

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Ara h 2 peptides containing dominant CD4+ T-cell epitopes: Candidates for a peanut allergy therapeutic

Cited by 84 publications

References 62 publications

In Silico Identification and in Vitro Analysis of B and T-Cell Epitopes of the Black Turtle Bean (Phaseolus Vulgaris L.) Lectin

In Silico Identification and in Vitro Analysis of B and T-Cell Epitopes of the Black Turtle Bean (Phaseolus Vulgaris L.) Lectin

Allergenic Properties of Enzymatically Hydrolyzed Peanut Flour Extracts

Unique and Cross-Reactive T Cell Epitope Peptides of the Major Bahia Grass Pollen Allergen, Pas n 1

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