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dc.creatorStanić-Vučinić, Dragana
dc.creatorStojadinović, Marija
dc.creatorMirkov, Ivana
dc.creatorApostolović, Danijela
dc.creatorBurazer, Lidija
dc.creatorAtanasković-Marković, Marina
dc.creatorKataranovski, Milena
dc.creatorĆirković-Veličković, Tanja
dc.date.accessioned2021-02-18T10:46:18Z
dc.date.available2021-02-18T10:46:18Z
dc.date.issued2016
dc.identifier.issn2046-2069
dc.identifier.urihttp://intor.torlakinstitut.com/handle/123456789/456
dc.description.abstractModified allergens are a safer and more efficient alternative to natural allergens for specific immunotherapy. As the modification of an allergen can diminish its immunogenicity due to the alteration of T-cell epitopes, in this paper we study the effects of a reversible chemical modification of Art v 1, the main allergen of mugwort pollen, on its allergenicity and immunogenicity. Modification of Art v 1 by cis-aconitylation into a polyanionic derivative (CAA) did not result in any significant structural alteration. However, IgE-binding epitopes on CAA were blocked, resulting in a reduced IgE-binding and basophil activation. Both proteins induced proliferation of CD3(+)CD4(+) T-cells in mugwort-allergic patients, but only unmodified allergens increased IL-4, IL-5 and IL-10 production. Rabbit and mouse anti-CAA antibodies exhibited cross-reactivity with native allergens and blocked human IgE-binding to Art v 1. Degradation of CAA by lysosomal fraction enzymes resulted in a similar set of peptides, harboring MHC class II-binding peptides, as unmodified proteins. Thus, cis-aconitylation modified Art v 1 had a significantly reduced allergenicity, whereas its immunogenicity was completely preserved. Acid-environment-responsive modification, which releases a full repertoire of native allergen epitopes within a particular site, can be considered a smart drug delivery system, which is able to deliver a therapeutically-effective dose in a controlled manner, and minimizes adverse side effects.en
dc.publisherRoyal Soc Chemistry, Cambridge
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172024/RS//
dc.relationinfo:eu-repo/grantAgreement/EC/FP7/256716/EU//
dc.rightsopenAccess
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/
dc.sourceRSC Advances
dc.titleHypoallergenic acid-sensitive modification preserves major mugwort allergen fold and delivers full repertoire of MHC class II-binding peptides during endolysosomal degradationen
dc.typearticle
dc.rights.licenseBY-NC
dc.citation.epage88228
dc.citation.issue91
dc.citation.other6(91): 88216-88228
dc.citation.rankM22
dc.citation.spage88216
dc.citation.volume6
dc.identifier.doi10.1039/c6ra17261j
dc.identifier.fulltexthttp://intor.torlakinstitut.com/bitstream/id/286/453.pdf
dc.identifier.rcubconv_394
dc.identifier.scopus2-s2.0-84988452156
dc.identifier.wos000384571800046
dc.type.versionpublishedVersion


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