Ara h 1 CD4+ T cell epitope-based peptides: candidates for a peanut allergy therapeutic
Identifieur interne : 002053 ( Main/Exploration ); précédent : 002052; suivant : 002054Ara 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
Affiliations:
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Phan</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Department of Immunology, Monash University</institution><addr-line>Melbourne, Vic., Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Melbourne, Vic.</wicri:regionArea><wicri:noRegion>Vic.</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="au2"><institution>Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital and Monash University</institution><addr-line>Melbourne, Vic., Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Melbourne, Vic.</wicri:regionArea><wicri:noRegion>Vic.</wicri:noRegion></affiliation></author><author><name sortKey="Dacumos Hill, A" sort="Dacumos Hill, A" uniqKey="Dacumos Hill A" first="A" last="Dacumos-Hill">A. 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Vic.</wicri:regionArea><wicri:noRegion>Vic.</wicri:noRegion></affiliation></author><author><name sortKey="O Hehir, R E" sort="O Hehir, R E" uniqKey="O Hehir R" first="R E" last="O'Hehir">R E O'Hehir</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Department of Immunology, Monash University</institution><addr-line>Melbourne, Vic., Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Melbourne, Vic.</wicri:regionArea><wicri:noRegion>Vic.</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="au2"><institution>Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital and Monash University</institution><addr-line>Melbourne, Vic., Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Melbourne, Vic.</wicri:regionArea><wicri:noRegion>Vic.</wicri:noRegion></affiliation></author></analytic><series><title level="j">Clinical and Experimental Allergy</title><idno type="ISSN">0954-7894</idno><idno type="eISSN">1365-2222</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Antigens, Plant (immunology)</term><term>Basophils (immunology)</term><term>CD4-Positive T-Lymphocytes (immunology)</term><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><term>Humans</term><term>Immunoglobulin E (blood)</term><term>Immunoglobulin E (immunology)</term><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></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Activation des lymphocytes (immunologie)</term><term>Antigènes d'histocompatibilité de classe II (immunologie)</term><term>Antigènes végétaux (immunologie)</term><term>Cartographie épitopique</term><term>Données de séquences moléculaires</term><term>Déterminants antigéniques des lymphocytes T ()</term><term>Déterminants antigéniques des lymphocytes T (immunologie)</term><term>Glycoprotéines (immunologie)</term><term>Granulocytes basophiles (immunologie)</term><term>Humains</term><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></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Immunoglobulin E</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Epitopes, T-Lymphocyte</term><term>Peptides</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antigens, Plant</term><term>Epitopes, T-Lymphocyte</term><term>Glycoproteins</term><term>Histocompatibility Antigens Class II</term><term>Immunoglobulin E</term><term>Peptides</term><term>Plant Proteins</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Activation des lymphocytes</term><term>Antigènes d'histocompatibilité de classe II</term><term>Antigènes végétaux</term><term>Déterminants antigéniques des lymphocytes T</term><term>Glycoprotéines</term><term>Granulocytes basophiles</term><term>Hypersensibilité à l'arachide</term><term>Immunoglobuline E</term><term>Lymphocytes T CD4+</term><term>Peptides</term><term>Protéines végétales</term></keywords><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></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Immunoglobuline E</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Epitope Mapping</term><term>Humans</term><term>Membrane Proteins</term><term>Molecular Sequence Data</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Cartographie épitopique</term><term>Données de séquences moléculaires</term><term>Déterminants antigéniques des lymphocytes T</term><term>Humains</term><term>Peptides</term><term>Protéines membranaires</term><term>Séquence d'acides aminés</term></keywords></textClass></profileDesc></teiHeader><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><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Bock, Sa" uniqKey="Bock S">SA Bock</name></author><author><name sortKey="Munoz Furlong, A" uniqKey="Munoz Furlong A">A Munoz-Furlong</name></author><author><name sortKey="Sampson, Ha" uniqKey="Sampson H">HA Sampson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Burks, Aw" uniqKey="Burks A">AW Burks</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sicherer, Sh" uniqKey="Sicherer S">SH 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sortKey="Hayball, Jd" uniqKey="Hayball J">JD Hayball</name></author><author><name sortKey="O Hehir, Re" uniqKey="O Hehir R">RE O'Hehir</name></author><author><name sortKey="Lamb, Jr" uniqKey="Lamb J">JR Lamb</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ruiter, B" uniqKey="Ruiter B">B Ruiter</name></author><author><name sortKey="Rozemuller, Eh" uniqKey="Rozemuller E">EH Rozemuller</name></author><author><name sortKey="Van Dijk, Aj" uniqKey="Van Dijk A">AJ van Dijk</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Neerven, Rj" uniqKey="Van Neerven R">RJ van Neerven</name></author><author><name sortKey="Van De Pol, Mm" uniqKey="Van De Pol M">MM van de Pol</name></author><author><name sortKey="Van Milligen, Fj" uniqKey="Van Milligen F">FJ van Milligen</name></author><author><name sortKey="Jansen, Hm" uniqKey="Jansen H">HM Jansen</name></author><author><name sortKey="Aalberse, Rc" uniqKey="Aalberse R">RC Aalberse</name></author><author><name sortKey="Kapsenberg, Ml" uniqKey="Kapsenberg M">ML Kapsenberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Larche, M" uniqKey="Larche M">M Larche</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rolland, Jm" uniqKey="Rolland J">JM Rolland</name></author><author><name sortKey="Gardner, Lm" uniqKey="Gardner L">LM Gardner</name></author><author><name sortKey="O Hehir, Re" uniqKey="O Hehir R">RE O'Hehir</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Burks, Aw" uniqKey="Burks A">AW Burks</name></author><author><name sortKey="Shin, D" uniqKey="Shin D">D Shin</name></author><author><name sortKey="Cockrell, G" uniqKey="Cockrell G">G Cockrell</name></author><author><name sortKey="Stanley, Js" uniqKey="Stanley J">JS Stanley</name></author><author><name sortKey="Helm, Rm" uniqKey="Helm R">RM Helm</name></author><author><name sortKey="Bannon, Ga" uniqKey="Bannon G">GA Bannon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shreffler, Wg" uniqKey="Shreffler W">WG Shreffler</name></author><author><name sortKey="Beyer, K" uniqKey="Beyer K">K Beyer</name></author><author><name sortKey="Chu, Th" uniqKey="Chu T">TH Chu</name></author><author><name sortKey="Burks, Aw" uniqKey="Burks A">AW Burks</name></author><author><name sortKey="Sampson, Ha" uniqKey="Sampson H">HA Sampson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Boxtel, El" uniqKey="Van Boxtel E">EL van Boxtel</name></author><author><name sortKey="Koppelman, Sj" uniqKey="Koppelman S">SJ Koppelman</name></author><author><name sortKey="Van Den Broek, La" uniqKey="Van Den Broek L">LA van den Broek</name></author><author><name sortKey="Gruppen, H" uniqKey="Gruppen H">H Gruppen</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Australie</li></country></list><tree><country name="Australie"><noRegion><name sortKey="Prickett, S R" sort="Prickett, S R" uniqKey="Prickett S" first="S R" last="Prickett">S R Prickett</name></noRegion><name sortKey="Dacumos Hill, A" sort="Dacumos Hill, A" uniqKey="Dacumos Hill A" first="A" last="Dacumos-Hill">A. Dacumos-Hill</name><name sortKey="Dacumos Hill, A" sort="Dacumos Hill, A" uniqKey="Dacumos Hill A" first="A" last="Dacumos-Hill">A. Dacumos-Hill</name><name sortKey="Mannering, S I" sort="Mannering, S I" uniqKey="Mannering S" first="S I" last="Mannering">S I Mannering</name><name sortKey="O Hehir, R E" sort="O Hehir, R E" uniqKey="O Hehir R" first="R E" last="O'Hehir">R E O'Hehir</name><name sortKey="O Hehir, R E" sort="O Hehir, R E" uniqKey="O Hehir R" first="R E" last="O'Hehir">R E O'Hehir</name><name sortKey="Phan, T" sort="Phan, T" uniqKey="Phan T" first="T" last="Phan">T. Phan</name><name sortKey="Phan, T" sort="Phan, T" uniqKey="Phan T" first="T" last="Phan">T. Phan</name><name sortKey="Prickett, S R" sort="Prickett, S R" uniqKey="Prickett S" first="S R" last="Prickett">S R Prickett</name><name sortKey="Rolland, J M" sort="Rolland, J M" uniqKey="Rolland J" first="J M" last="Rolland">J M Rolland</name><name sortKey="Rolland, J M" sort="Rolland, J M" uniqKey="Rolland J" first="J M" last="Rolland">J M Rolland</name><name sortKey="Voskamp, A L" sort="Voskamp, A L" uniqKey="Voskamp A" first="A L" last="Voskamp">A L Voskamp</name><name sortKey="Voskamp, A L" sort="Voskamp, A L" uniqKey="Voskamp A" first="A L" last="Voskamp">A L Voskamp</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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