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Plasmodium falciparum Rosetting Epitopes Converge in the SD3-Loop of PfEMP1-DBL1α

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dc.audienceComunidad Rosaristaspa
dc.creatorAngeletti, Davide
dc.creatorAlbrecht, Letusa
dc.creatorBlomqvist, Karin
dc.creatorQuintana, María del Pilar
dc.creatorAkhter, Tahmina
dc.creatorBächle, Susanna
dc.creatorSawyer, Alan
dc.creatorSandalova, Tatyana
dc.creatorAchour, Adnane
dc.creatorWahlgren, Mats
dc.creatorMoll, Kirsten
dc.creator.googleAngeletti, Davide
dc.creator.googleAlbrecht, Letusa
dc.creator.googleBlomqvist, Karin
dc.creator.googleQuintana, María del Pilar
dc.creator.googleAkhter, Tahmina
dc.creator.googleBächle, Susanna M.
dc.creator.googleSawyer, Alan
dc.creator.googleSandalova, Tatyana
dc.creator.googleAchour, Adnane
dc.creator.googleWahlgren, Mats
dc.creator.googleMoll, Kirsten
dc.date.accessioned2014-08-11T18:51:32Z
dc.date.available2014-08-11T18:51:32Z
dc.date.created2012-12-05
dc.date.issued2012
dc.description.abstractThe ability of Plasmodium falciparum parasitized RBC (pRBC) to form rosettes with normal RBC is linked to the virulence of the parasite and RBC polymorphisms that weaken rosetting confer protection against severe malaria. The adhesin PfEMP1 mediates the binding and specific antibodies prevent sequestration in the micro-vasculature, as seen in animal models. Here we demonstrate that epitopes targeted by rosette disrupting antibodies converge in the loop of subdomain 3 (SD3) which connects the h6 and h7 α-helices of PfEMP1-DBL1α. Both monoclonal antibodies and polyclonal IgG, that bound to epitopes in the SD3-loop, stained the surface of pRBC, disrupted rosettes and blocked direct binding of recombinant NTS-DBL1α to RBC. Depletion of polyclonal IgG raised to NTS-DBL1α on a SD3 loop-peptide removed the anti-rosetting activity. Immunizations with recombinant subdomain 1 (SD1), subdomain 2 (SD2) or SD3 all generated antibodies reacting with the pRBC-surface but only the sera of animals immunized with SD3 disrupted rosettes. SD3-sequences were found to segregate phylogenetically into two groups (A/B). Group A included rosetting sequences that were associated with two cysteine-residues present in the SD2-domain while group B included those with three or more cysteines. Our results suggest that the SD3 loop of PfEMP1-DBL1α is an important target of anti-rosetting activity, clarifying the molecular basis of the development of variant-specific rosette disrupting antibodies.eng
dc.format.mediumRecurso electrónicospa
dc.format.mimetypeapplication/pdf
dc.format.tipoDocumentospa
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0050758
dc.identifier.issnISSN:1932-6203
dc.identifier.urihttp://repository.urosario.edu.co/handle/10336/8774
dc.language.isoeng
dc.publisherUniversidad del Rosariospa
dc.relation.citationIssueNo. 12
dc.relation.citationTitlePLOS ONE
dc.relation.citationVolumeVol. 7
dc.relation.ispartofPLOS ONE ISSN: 1932-6203 V. 7 N. 12 Dic, 2012spa
dc.relation.urihttp://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0050758&representation=PDF
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto completo)spa
dc.rights.licenciaEL AUTOR, manifiesta que la obra objeto de la presente autorización es original y la realizó sin violar o usurpar derechos de autor de terceros, por lo tanto la obra es de exclusiva autoría y tiene la titularidad sobre la misma.spa
dc.source.instnameinstname:Universidad del Rosariospa
dc.source.reponamereponame:Repositorio Institucional EdocURspa
dc.subject.ddcIncidencia & prevención de la enfermedad
dc.subject.decsPlasmodium falciparumspa
dc.subject.decsMalariaspa
dc.subject.decsParasitosisspa
dc.subject.decsInmunologíaspa
dc.subject.keywordAntibodieseng
dc.subject.keywordEnzyme-linked immunoassayseng
dc.subject.keywordFlow cytometryeng
dc.subject.keywordRecombinant proteinseng
dc.subject.keywordMalariaeng
dc.subject.keywordMalarial parasiteseng
dc.subject.keywordRecombination reactionseng
dc.subject.keywordRed blood cellseng
dc.titlePlasmodium falciparum Rosetting Epitopes Converge in the SD3-Loop of PfEMP1-DBL1αspa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/acceptedVersion
dc.type.spaArtículospa
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