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High non-protective, long-lasting antibody levels in malaria are associated with haplotype shifting in MHC-peptide-TCR complex formation: a new mechanism for immune evasion

dc.creatorPatarroyo, Manuel E.spa
dc.creatorBermudez, Adriana
dc.creatorSalazar, Luz Maryspa
dc.creatorEspejo, Fabiolaspa
dc.date.accessioned2020-08-06T16:20:15Z
dc.date.available2020-08-06T16:20:15Z
dc.date.created2006-07spa
dc.description.abstractAn effective malarial vaccine must contain multiple immunogenic, protection-inducing epitopes able to block and destroy the P. falciparum malaria parasite, the most lethal form of this disease in the world. Our strategy has consisted in using conserved peptides blocking parasite binding to red blood cells; however, these peptides are non-immunogenic and non-protection-inducing. Modifying their critical residues can make them immunogenic. Such peptides induced antibody titers (determined by immunofluorescence antibody test, IFA) and made the latter reactive (determined by Western blot) and protection inducing against experimental challenge with a highly infective Aotus monkey adapted P. falciparum strain. Modified peptides also induce highly non-protective long-lasting antibody levels. Modifications performed might allow them to bind specifically to different HLA-DR? purified molecules. These immunological and biological activities are associated with modifications in their three-dimensional structure as determined by 1H-NMR. It was found that modified, high non-protective long-lasting antibody level peptides bound to HLA-DR molecules from a different haplotype (to which immunogenic, protection-inducers bind) and had 4.6 ± 1.4 Å shorter distances between residues fitting into these molecules' Pocket 1 to Pocket 9, suggesting fitting into an inappropriate HLA-DR molecule. A multi-component, subunit-based, malarial vaccine is therefore feasible if modified peptides are suitably modified for an appropriate fit into the correct HLA-DR?1* molecule in order to form a proper MHC-II–peptide–TCR complex.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1016/j.biochi.2006.01.005
dc.identifier.issnISSN: 0300-9084
dc.identifier.issnEISSN: 6183-1638
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/25934
dc.language.isoengspa
dc.publisherElsevierspa
dc.relation.citationEndPage784
dc.relation.citationIssueNo. 7
dc.relation.citationStartPage775
dc.relation.citationTitleBiochimie
dc.relation.citationVolumeVol. 88
dc.relation.ispartofBiochimie, ISSN: 0300-9084;EISSN: 6183-1638, Vol.88 No.7 (2006); pp.775-784spa
dc.relation.urihttps://www.sciencedirect.com/science/article/abs/pii/S030090840600006X?via%3Dihubspa
dc.rights.accesRightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.accesoRestringido (Acceso a grupos específicos)spa
dc.sourceBiochimiespa
dc.source.instnameinstname:Universidad del Rosario
dc.source.reponamereponame:Repositorio Institucional EdocUR
dc.subject.keywordMalaria vaccinespa
dc.subject.keywordImmunogenic peptidesspa
dc.subject.keywordMHC II-peptide-TCR Complexspa
dc.subject.keywordLong-lasting antibodyspa
dc.titleHigh non-protective, long-lasting antibody levels in malaria are associated with haplotype shifting in MHC-peptide-TCR complex formation: a new mechanism for immune evasionspa
dc.title.TranslatedTitleLos altos niveles de anticuerpos no protectores y duraderos en la malaria están asociados con el cambio de haplotipos en la formación del complejo MHC-péptido-TCR: un nuevo mecanismo para la evasión inmunespa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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