B-Cell Epitopes in NTS-DBL1 alpha of PfEMP1 Recognized by Human Antibodies in Rosetting Plasmodium falciparum
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/38481 http://dx.doi.org/10.1371/journal.pone.0113248 |
Resumo: | Plasmodium falciparum is the most lethal of the human malaria parasites. the virulence is associated with the capacity of the infected red blood cell (iRBC) to sequester inside the deep microvasculature where it may cause obstruction of the blood-flow when binding is excessive. Rosetting, the adherence of the iRBC to uninfected erythrocytes, has been found associated with severe malaria and found to be mediated by the NTS-DBL1 alpha-domain of Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1). Here we show that the reactivity of plasma of Cameroonian children with the surface of the FCR3S1.2-iRBC correlated with the capacity to disrupt rosettes and with the antibody reactivity with a recombinant PfEMP1 (NTS-DBL1 alpha of IT4(var60)) expressed by parasite FCR3S1.2. the plasma-reactivity in a microarray, consisting of 96 overlapping 15-mer long peptides covering the NTS-DBL1 alpha domain from IT4var60 sequence, was compared with their capacity to disrupt rosettes and we identified five peptides where the reactivity were correlated. Three of the peptides were localized in subdomain-1 and 2. the other two peptide-sequences were localized in the NTS-domain and in subdomain-3. Further, principal component analysis and orthogonal partial least square analysis generated a model that supported these findings. in conclusion, human antibody reactivity with short linear-peptides of NTS-DBL1 alpha of PfEMP1 suggests subdomains 1 and 2 to hold anti-rosetting epitopes recognized by anti-rosetting antibodies. the data suggest rosetting to be mediated by the variable areas of PfEMP1 but also to involve structurally relatively conserved areas of the molecule that may induce biologically active antibodies. |
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Albrecht, Letusa [UNIFESP]Angeletti, DavideMoll, KirstenBlomqvist, KarinValentini, DavideD'Alexandri, Fabio LuizMaurer, MarkusWahlgren, MatsKarolinska InstKarolinska Univ HospUniversidade Estadual de Campinas (UNICAMP)Universidade Federal de São Paulo (UNIFESP)2016-01-24T14:38:13Z2016-01-24T14:38:13Z2014-12-01Plos One. San Francisco: Public Library Science, v. 9, n. 12, 26 p., 2014.1932-6203http://repositorio.unifesp.br/handle/11600/38481http://dx.doi.org/10.1371/journal.pone.0113248WOS000347114900036.pdf10.1371/journal.pone.0113248WOS:000347114900036Plasmodium falciparum is the most lethal of the human malaria parasites. the virulence is associated with the capacity of the infected red blood cell (iRBC) to sequester inside the deep microvasculature where it may cause obstruction of the blood-flow when binding is excessive. Rosetting, the adherence of the iRBC to uninfected erythrocytes, has been found associated with severe malaria and found to be mediated by the NTS-DBL1 alpha-domain of Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1). Here we show that the reactivity of plasma of Cameroonian children with the surface of the FCR3S1.2-iRBC correlated with the capacity to disrupt rosettes and with the antibody reactivity with a recombinant PfEMP1 (NTS-DBL1 alpha of IT4(var60)) expressed by parasite FCR3S1.2. the plasma-reactivity in a microarray, consisting of 96 overlapping 15-mer long peptides covering the NTS-DBL1 alpha domain from IT4var60 sequence, was compared with their capacity to disrupt rosettes and we identified five peptides where the reactivity were correlated. Three of the peptides were localized in subdomain-1 and 2. the other two peptide-sequences were localized in the NTS-domain and in subdomain-3. Further, principal component analysis and orthogonal partial least square analysis generated a model that supported these findings. in conclusion, human antibody reactivity with short linear-peptides of NTS-DBL1 alpha of PfEMP1 suggests subdomains 1 and 2 to hold anti-rosetting epitopes recognized by anti-rosetting antibodies. the data suggest rosetting to be mediated by the variable areas of PfEMP1 but also to involve structurally relatively conserved areas of the molecule that may induce biologically active antibodies.Swedish Research Council (VR)Swedish Academy of Sciences (KVA, Soderberg Foundation)Karolinska Institutet-DPAEU Network of Excellence EviMalarKarolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, Stockholm, SwedenKarolinska Inst, Dept Lab Med, Therapeut Immunol TIM, Stockholm, SwedenKarolinska Univ Hosp, CAST, Huddinge, SwedenUniv Estadual Campinas, Dept Biochem, Campinas, SP, BrazilUniversidade Federal de São Paulo, EPM, São Paulo, BrazilWeb of Science26engPublic Library SciencePlos OneB-Cell Epitopes in NTS-DBL1 alpha of PfEMP1 Recognized by Human Antibodies in Rosetting Plasmodium falciparuminfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000347114900036.pdfapplication/pdf2203323${dspace.ui.url}/bitstream/11600/38481/1/WOS000347114900036.pdf445db9fbc6fa74d960e65227f0b84c4dMD51open accessTEXTWOS000347114900036.pdf.txtWOS000347114900036.pdf.txtExtracted texttext/plain64942${dspace.ui.url}/bitstream/11600/38481/2/WOS000347114900036.pdf.txtfde8e93e6b539e4a2021cda7863df56aMD52open access11600/384812022-11-04 15:20:26.713open accessoai:repositorio.unifesp.br:11600/38481Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-11-04T18:20:26Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
B-Cell Epitopes in NTS-DBL1 alpha of PfEMP1 Recognized by Human Antibodies in Rosetting Plasmodium falciparum |
title |
B-Cell Epitopes in NTS-DBL1 alpha of PfEMP1 Recognized by Human Antibodies in Rosetting Plasmodium falciparum |
spellingShingle |
B-Cell Epitopes in NTS-DBL1 alpha of PfEMP1 Recognized by Human Antibodies in Rosetting Plasmodium falciparum Albrecht, Letusa [UNIFESP] |
title_short |
B-Cell Epitopes in NTS-DBL1 alpha of PfEMP1 Recognized by Human Antibodies in Rosetting Plasmodium falciparum |
title_full |
B-Cell Epitopes in NTS-DBL1 alpha of PfEMP1 Recognized by Human Antibodies in Rosetting Plasmodium falciparum |
title_fullStr |
B-Cell Epitopes in NTS-DBL1 alpha of PfEMP1 Recognized by Human Antibodies in Rosetting Plasmodium falciparum |
title_full_unstemmed |
B-Cell Epitopes in NTS-DBL1 alpha of PfEMP1 Recognized by Human Antibodies in Rosetting Plasmodium falciparum |
title_sort |
B-Cell Epitopes in NTS-DBL1 alpha of PfEMP1 Recognized by Human Antibodies in Rosetting Plasmodium falciparum |
author |
Albrecht, Letusa [UNIFESP] |
author_facet |
Albrecht, Letusa [UNIFESP] Angeletti, Davide Moll, Kirsten Blomqvist, Karin Valentini, Davide D'Alexandri, Fabio Luiz Maurer, Markus Wahlgren, Mats |
author_role |
author |
author2 |
Angeletti, Davide Moll, Kirsten Blomqvist, Karin Valentini, Davide D'Alexandri, Fabio Luiz Maurer, Markus Wahlgren, Mats |
author2_role |
author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Karolinska Inst Karolinska Univ Hosp Universidade Estadual de Campinas (UNICAMP) Universidade Federal de São Paulo (UNIFESP) |
dc.contributor.author.fl_str_mv |
Albrecht, Letusa [UNIFESP] Angeletti, Davide Moll, Kirsten Blomqvist, Karin Valentini, Davide D'Alexandri, Fabio Luiz Maurer, Markus Wahlgren, Mats |
description |
Plasmodium falciparum is the most lethal of the human malaria parasites. the virulence is associated with the capacity of the infected red blood cell (iRBC) to sequester inside the deep microvasculature where it may cause obstruction of the blood-flow when binding is excessive. Rosetting, the adherence of the iRBC to uninfected erythrocytes, has been found associated with severe malaria and found to be mediated by the NTS-DBL1 alpha-domain of Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1). Here we show that the reactivity of plasma of Cameroonian children with the surface of the FCR3S1.2-iRBC correlated with the capacity to disrupt rosettes and with the antibody reactivity with a recombinant PfEMP1 (NTS-DBL1 alpha of IT4(var60)) expressed by parasite FCR3S1.2. the plasma-reactivity in a microarray, consisting of 96 overlapping 15-mer long peptides covering the NTS-DBL1 alpha domain from IT4var60 sequence, was compared with their capacity to disrupt rosettes and we identified five peptides where the reactivity were correlated. Three of the peptides were localized in subdomain-1 and 2. the other two peptide-sequences were localized in the NTS-domain and in subdomain-3. Further, principal component analysis and orthogonal partial least square analysis generated a model that supported these findings. in conclusion, human antibody reactivity with short linear-peptides of NTS-DBL1 alpha of PfEMP1 suggests subdomains 1 and 2 to hold anti-rosetting epitopes recognized by anti-rosetting antibodies. the data suggest rosetting to be mediated by the variable areas of PfEMP1 but also to involve structurally relatively conserved areas of the molecule that may induce biologically active antibodies. |
publishDate |
2014 |
dc.date.issued.fl_str_mv |
2014-12-01 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:38:13Z |
dc.date.available.fl_str_mv |
2016-01-24T14:38:13Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Plos One. San Francisco: Public Library Science, v. 9, n. 12, 26 p., 2014. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/38481 http://dx.doi.org/10.1371/journal.pone.0113248 |
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1932-6203 |
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WOS000347114900036.pdf |
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10.1371/journal.pone.0113248 |
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WOS:000347114900036 |
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Plos One. San Francisco: Public Library Science, v. 9, n. 12, 26 p., 2014. 1932-6203 WOS000347114900036.pdf 10.1371/journal.pone.0113248 WOS:000347114900036 |
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