Ara h 1 CD4+ T cell epitope-based peptides: candidates for a peanut allergy therapeutic
Identifieur interne : 000A50 ( Ncbi/Curation ); précédent : 000A49; suivant : 000A51Ara h 1 CD4+ T cell epitope-based peptides: candidates for a peanut allergy therapeutic
Auteurs : S R Prickett [Australie] ; A L Voskamp [Australie] ; T. Phan [Australie] ; A. Dacumos-Hill [Australie] ; S I Mannering [Australie] ; J M Rolland [Australie] ; R E O'Hehir [Australie]Source :
- Clinical and Experimental Allergy [ 0954-7894 ] ; 2013.
Descripteurs français
- KwdFr :
- Activation des lymphocytes (immunologie), Antigènes d'histocompatibilité de classe II (immunologie), Antigènes végétaux (immunologie), Cartographie épitopique, Données de séquences moléculaires, Déterminants antigéniques des lymphocytes T (), Déterminants antigéniques des lymphocytes T (immunologie), Glycoprotéines (immunologie), Granulocytes basophiles (immunologie), Humains, Hypersensibilité à l'arachide (immunologie), Immunoglobuline E (immunologie), Immunoglobuline E (sang), Lymphocytes T CD4+ (immunologie), Peptides (), Peptides (immunologie), Protéines membranaires, Protéines végétales (immunologie), Séquence d'acides aminés.
- MESH :
- immunologie : Activation des lymphocytes, Antigènes d'histocompatibilité de classe II, Antigènes végétaux, Déterminants antigéniques des lymphocytes T, Glycoprotéines, Granulocytes basophiles, Hypersensibilité à l'arachide, Immunoglobuline E, Lymphocytes T CD4+, Peptides, Protéines végétales.
- sang : Immunoglobuline E.
- Cartographie épitopique, Données de séquences moléculaires, Déterminants antigéniques des lymphocytes T, Humains, Peptides, Protéines membranaires, Séquence d'acides aminés.
English descriptors
- KwdEn :
- Amino Acid Sequence, Antigens, Plant (immunology), Basophils (immunology), CD4-Positive T-Lymphocytes (immunology), Epitope Mapping, Epitopes, T-Lymphocyte (chemistry), Epitopes, T-Lymphocyte (immunology), Glycoproteins (immunology), Histocompatibility Antigens Class II (immunology), Humans, Immunoglobulin E (blood), Immunoglobulin E (immunology), Lymphocyte Activation (immunology), Membrane Proteins, Molecular Sequence Data, Peanut Hypersensitivity (immunology), Peptides (chemistry), Peptides (immunology), Plant Proteins (immunology).
- MESH :
- chemical , blood : Immunoglobulin E.
- chemical , chemistry : Epitopes, T-Lymphocyte, Peptides.
- chemical , immunology : Antigens, Plant, Epitopes, T-Lymphocyte, Glycoproteins, Histocompatibility Antigens Class II, Immunoglobulin E, Peptides, Plant Proteins.
- immunology : Basophils, CD4-Positive T-Lymphocytes, Lymphocyte Activation, Peanut Hypersensitivity.
- Amino Acid Sequence, Epitope Mapping, Humans, Membrane Proteins, Molecular Sequence Data.
Abstract
Peanut allergy is a life-threatening condition; there is currently no cure. While whole allergen extracts are used for specific immunotherapy for many allergies, they can cause severe reactions and even fatalities in peanut allergy.
To identify short, HLA-degenerate CD4+ T cell epitope-based peptides of the major peanut allergen Ara h 1 that target allergen-specific T cells without causing IgE-mediated inflammatory cell activation, as candidates for safe peanut-specific immunotherapy.
Ara h 1-specific CD4+ T cell lines (TCL) were generated from peripheral blood mononuclear cells (PBMC) of peanut-allergic subjects using CFSE-based methodology. T cell epitopes were identified using CFSE and thymidine-based proliferation assays. Epitope HLA-restriction was investigated using blocking antibodies, HLA-genotyping and epitope prediction algorithms. Functional peanut-specific IgE reactivity to peptides was assessed by basophil activation assay.
A total of 145 Ara h 1-specific TCL were generated from 18 HLA-diverse peanut-allergic subjects. The TCL recognized 20-mer peptides throughout Ara h 1. Nine 20-mers containing the most frequently recognized epitopes were selected and their recognition confirmed in 18 additional peanut-allergic subjects. Ten core epitopes were mapped within these 20-mers. These were HLA-DQ and/or HLA–DR restricted, with each presented on at least two different HLA-molecules. Seven short (≤ 20 aa) non-basophil-reactive peptides encompassing all core epitopes were designed and validated in peanut-allergic donor PBMC T cell assays.
Short CD4+ T cell epitope-based Ara h 1 peptides were identified as novel candidates for a safe, T cell targeted peanut-specific immunotherapy for HLA-diverse populations.
Url:
DOI: 10.1111/cea.12113
PubMed: 23711131
PubMed Central: 3709139
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PMC:3709139Le document en format XML
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<term>Epitope Mapping</term>
<term>Epitopes, T-Lymphocyte (chemistry)</term>
<term>Epitopes, T-Lymphocyte (immunology)</term>
<term>Glycoproteins (immunology)</term>
<term>Histocompatibility Antigens Class II (immunology)</term>
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<term>Lymphocyte Activation (immunology)</term>
<term>Membrane Proteins</term>
<term>Molecular Sequence Data</term>
<term>Peanut Hypersensitivity (immunology)</term>
<term>Peptides (chemistry)</term>
<term>Peptides (immunology)</term>
<term>Plant Proteins (immunology)</term>
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<keywords scheme="KwdFr" xml:lang="fr"><term>Activation des lymphocytes (immunologie)</term>
<term>Antigènes d'histocompatibilité de classe II (immunologie)</term>
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<term>Granulocytes basophiles (immunologie)</term>
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<term>Hypersensibilité à l'arachide (immunologie)</term>
<term>Immunoglobuline E (immunologie)</term>
<term>Immunoglobuline E (sang)</term>
<term>Lymphocytes T CD4+ (immunologie)</term>
<term>Peptides ()</term>
<term>Peptides (immunologie)</term>
<term>Protéines membranaires</term>
<term>Protéines végétales (immunologie)</term>
<term>Séquence d'acides aminés</term>
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<term>Déterminants antigéniques des lymphocytes T</term>
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<term>Hypersensibilité à l'arachide</term>
<term>Immunoglobuline E</term>
<term>Lymphocytes T CD4+</term>
<term>Peptides</term>
<term>Protéines végétales</term>
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<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Basophils</term>
<term>CD4-Positive T-Lymphocytes</term>
<term>Lymphocyte Activation</term>
<term>Peanut Hypersensitivity</term>
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<term>Epitope Mapping</term>
<term>Humans</term>
<term>Membrane Proteins</term>
<term>Molecular Sequence Data</term>
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<term>Données de séquences moléculaires</term>
<term>Déterminants antigéniques des lymphocytes T</term>
<term>Humains</term>
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>Peanut allergy is a life-threatening condition; there is currently no cure. While whole allergen extracts are used for specific immunotherapy for many allergies, they can cause severe reactions and even fatalities in peanut allergy.</p>
</sec>
<sec><title>Objective</title>
<p>To identify short, HLA-degenerate CD4<sup>+</sup>
T cell epitope-based peptides of the major peanut allergen Ara h 1 that target allergen-specific T cells without causing IgE-mediated inflammatory cell activation, as candidates for safe peanut-specific immunotherapy.</p>
</sec>
<sec><title>Methods</title>
<p>Ara h 1-specific CD4<sup>+</sup>
T cell lines (TCL) were generated from peripheral blood mononuclear cells (PBMC) of peanut-allergic subjects using CFSE-based methodology. T cell epitopes were identified using CFSE and thymidine-based proliferation assays. Epitope HLA-restriction was investigated using blocking antibodies, HLA-genotyping and epitope prediction algorithms. Functional peanut-specific IgE reactivity to peptides was assessed by basophil activation assay.</p>
</sec>
<sec><title>Results</title>
<p>A total of 145 Ara h 1-specific TCL were generated from 18 HLA-diverse peanut-allergic subjects. The TCL recognized 20-mer peptides throughout Ara h 1. Nine 20-mers containing the most frequently recognized epitopes were selected and their recognition confirmed in 18 additional peanut-allergic subjects. Ten core epitopes were mapped within these 20-mers. These were HLA-DQ and/or HLA–DR restricted, with each presented on at least two different HLA-molecules. Seven short (≤ 20 aa) non-basophil-reactive peptides encompassing all core epitopes were designed and validated in peanut-allergic donor PBMC T cell assays.</p>
</sec>
<sec><title>Conclusions and Clinical Relevance</title>
<p>Short CD4<sup>+</sup>
T cell epitope-based Ara h 1 peptides were identified as novel candidates for a safe, T cell targeted peanut-specific immunotherapy for HLA-diverse populations.</p>
</sec>
</div>
</front>
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