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Comparisons of Allergenic and Metazoan Parasite Proteins: Allergy the Price of Immunity.

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cam.depositDate2022-01-18
cam.issuedOnline2015-10-29
dc.contributor.authorTyagi, Nidhi
dc.contributor.authorFarnell, Edward J
dc.contributor.authorFitzsimmons, Colin M
dc.contributor.authorRyan, Stephanie
dc.contributor.authorTukahebwa, Edridah
dc.contributor.authorMaizels, Rick M
dc.contributor.authorDunne, David W
dc.contributor.authorThornton, Janet M
dc.contributor.authorFurnham, Nicholas
dc.contributor.orcidFarnell, Edward John [0000-0001-5996-7345]
dc.contributor.orcidDunne, David [0000-0002-8940-9886]
dc.date.accessioned2022-01-22T00:30:38Z
dc.date.available2022-01-22T00:30:38Z
dc.date.issued2015-10
dc.date.updated2022-01-18T14:42:45Z
dc.description.abstractAllergic reactions can be considered as maladaptive IgE immune responses towards environmental antigens. Intriguingly, these mechanisms are observed to be very similar to those implicated in the acquisition of an important degree of immunity against metazoan parasites (helminths and arthropods) in mammalian hosts. Based on the hypothesis that IgE-mediated immune responses evolved in mammals to provide extra protection against metazoan parasites rather than to cause allergy, we predict that the environmental allergens will share key properties with the metazoan parasite antigens that are specifically targeted by IgE in infected human populations. We seek to test this prediction by examining if significant similarity exists between molecular features of allergens and helminth proteins that induce an IgE response in the human host. By employing various computational approaches, 2712 unique protein molecules that are known IgE antigens were searched against a dataset of proteins from helminths and parasitic arthropods, resulting in a comprehensive list of 2445 parasite proteins that show significant similarity through sequence and structure with allergenic proteins. Nearly half of these parasite proteins from 31 species fall within the 10 most abundant allergenic protein domain families (EF-hand, Tropomyosin, CAP, Profilin, Lipocalin, Trypsin-like serine protease, Cupin, BetV1, Expansin and Prolamin). We identified epitopic-like regions in 206 parasite proteins and present the first example of a plant protein (BetV1) that is the commonest allergen in pollen in a worm, and confirming it as the target of IgE in schistosomiasis infected humans. The identification of significant similarity, inclusive of the epitopic regions, between allergens and helminth proteins against which IgE is an observed marker of protective immunity explains the 'off-target' effects of the IgE-mediated immune system in allergy. All these findings can impact the discovery and design of molecules used in immunotherapy of allergic conditions.
dc.format.mediumElectronic-eCollection
dc.identifier.doi10.17863/CAM.80298
dc.identifier.eissn1553-7358
dc.identifier.issn1553-734X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332868
dc.language.isoeng
dc.publisherPublic Library of Science (PLoS)
dc.publisher.departmentDepartment of Pathology
dc.publisher.urlhttp://dx.doi.org/10.1371/journal.pcbi.1004546
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAllergens
dc.subjectAnimals
dc.subjectAntigens, Helminth
dc.subjectEvolution, Molecular
dc.subjectHelminth Proteins
dc.subjectHelminths
dc.subjectHumans
dc.subjectHypersensitivity
dc.subjectImmunity, Innate
dc.subjectImmunoglobulin E
dc.titleComparisons of Allergenic and Metazoan Parasite Proteins: Allergy the Price of Immunity.
dc.typeArticle
dcterms.dateAccepted2015-08-24
prism.issueIdentifier10
prism.numberARTN e1004546
prism.publicationDate2015
prism.publicationNamePLoS Comput Biol
prism.startingPagee1004546
prism.volume11
pubs.funder-project-idWellcome Trust (094317/Z/10/Z)
pubs.funder-project-idWellcome Trust (083931/Z/07/Z)
pubs.funder-project-idEuropean Commission (242107)
pubs.licence-display-nameApollo Repository Deposit Licence Agreement
pubs.licence-identifierapollo-deposit-licence-2-1
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1371/journal.pcbi.1004546

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