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Human pregnancy-associated malaria-specific B cells target polymorphic, conformational epitopes in VAR2CSA

Pregnancy-associated malaria (PAM) is caused by Plasmodium falciparum-infected erythrocytes (IEs) that bind to chondroitin sulphate A (CSA) in the placenta by PAM-associated clonally variant surface antigens (VSA). Pregnancy-specific VSA (VSA(PAM)), which include the PfEMP1 variant VAR2CSA, are targ...

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Autores principales: Barfod, Lea, Bernasconi, Nadia L, Dahlbäck, Madeleine, Jarrossay, David, Andersen, Pernille Haste, Salanti, Ali, Ofori, Michael F, Turner, Louise, Resende, Mafalda, Nielsen, Morten A, Theander, Thor G, Sallusto, Federica, Lanzavecchia, Antonio, Hviid, Lars
Formato: Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2779471/
https://www.ncbi.nlm.nih.gov/pubmed/17176260
http://dx.doi.org/10.1111/j.1365-2958.2006.05503.x
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author Barfod, Lea
Bernasconi, Nadia L
Dahlbäck, Madeleine
Jarrossay, David
Andersen, Pernille Haste
Salanti, Ali
Ofori, Michael F
Turner, Louise
Resende, Mafalda
Nielsen, Morten A
Theander, Thor G
Sallusto, Federica
Lanzavecchia, Antonio
Hviid, Lars
author_facet Barfod, Lea
Bernasconi, Nadia L
Dahlbäck, Madeleine
Jarrossay, David
Andersen, Pernille Haste
Salanti, Ali
Ofori, Michael F
Turner, Louise
Resende, Mafalda
Nielsen, Morten A
Theander, Thor G
Sallusto, Federica
Lanzavecchia, Antonio
Hviid, Lars
author_sort Barfod, Lea
collection PubMed
description Pregnancy-associated malaria (PAM) is caused by Plasmodium falciparum-infected erythrocytes (IEs) that bind to chondroitin sulphate A (CSA) in the placenta by PAM-associated clonally variant surface antigens (VSA). Pregnancy-specific VSA (VSA(PAM)), which include the PfEMP1 variant VAR2CSA, are targets of IgG-mediated protective immunity to PAM. Here, we report an investigation of the specificity of naturally acquired immunity to PAM, using eight human monoclonal IgG1 antibodies that react exclusively with intact CSA-adhering IEs expressing VSA(PAM). Four reacted in Western blotting with high-molecular-weight (> 200 kDa) proteins, while seven reacted with either the DBL3-X or the DBL5-ε domains of VAR2CSA expressed either as Baculovirus constructs or on the surface of transfected Jurkat cells. We used a panel of recombinant antigens representing DBL3-X domains from P. falciparum field isolates to evaluate B-cell epitope diversity among parasite isolates, and identified the binding site of one monoclonal antibody using a chimeric DBL3-X construct. Our findings show that there is a high-frequency memory response to VSA(PAM), indicating that VAR2CSA is a primary target of naturally acquired PAM-specific protective immunity, and demonstrate the value of human monoclonal antibodies and conformationally intact recombinant antigens in VSA characterization.
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spelling pubmed-27794712009-11-24 Human pregnancy-associated malaria-specific B cells target polymorphic, conformational epitopes in VAR2CSA Barfod, Lea Bernasconi, Nadia L Dahlbäck, Madeleine Jarrossay, David Andersen, Pernille Haste Salanti, Ali Ofori, Michael F Turner, Louise Resende, Mafalda Nielsen, Morten A Theander, Thor G Sallusto, Federica Lanzavecchia, Antonio Hviid, Lars Mol Microbiol Research Articles Pregnancy-associated malaria (PAM) is caused by Plasmodium falciparum-infected erythrocytes (IEs) that bind to chondroitin sulphate A (CSA) in the placenta by PAM-associated clonally variant surface antigens (VSA). Pregnancy-specific VSA (VSA(PAM)), which include the PfEMP1 variant VAR2CSA, are targets of IgG-mediated protective immunity to PAM. Here, we report an investigation of the specificity of naturally acquired immunity to PAM, using eight human monoclonal IgG1 antibodies that react exclusively with intact CSA-adhering IEs expressing VSA(PAM). Four reacted in Western blotting with high-molecular-weight (> 200 kDa) proteins, while seven reacted with either the DBL3-X or the DBL5-ε domains of VAR2CSA expressed either as Baculovirus constructs or on the surface of transfected Jurkat cells. We used a panel of recombinant antigens representing DBL3-X domains from P. falciparum field isolates to evaluate B-cell epitope diversity among parasite isolates, and identified the binding site of one monoclonal antibody using a chimeric DBL3-X construct. Our findings show that there is a high-frequency memory response to VSA(PAM), indicating that VAR2CSA is a primary target of naturally acquired PAM-specific protective immunity, and demonstrate the value of human monoclonal antibodies and conformationally intact recombinant antigens in VSA characterization. Blackwell Publishing Ltd 2007-01 /pmc/articles/PMC2779471/ /pubmed/17176260 http://dx.doi.org/10.1111/j.1365-2958.2006.05503.x Text en © 2006 The Authors; Journal compilation © 2006 Blackwell Publishing Ltd http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
spellingShingle Research Articles
Barfod, Lea
Bernasconi, Nadia L
Dahlbäck, Madeleine
Jarrossay, David
Andersen, Pernille Haste
Salanti, Ali
Ofori, Michael F
Turner, Louise
Resende, Mafalda
Nielsen, Morten A
Theander, Thor G
Sallusto, Federica
Lanzavecchia, Antonio
Hviid, Lars
Human pregnancy-associated malaria-specific B cells target polymorphic, conformational epitopes in VAR2CSA
title Human pregnancy-associated malaria-specific B cells target polymorphic, conformational epitopes in VAR2CSA
title_full Human pregnancy-associated malaria-specific B cells target polymorphic, conformational epitopes in VAR2CSA
title_fullStr Human pregnancy-associated malaria-specific B cells target polymorphic, conformational epitopes in VAR2CSA
title_full_unstemmed Human pregnancy-associated malaria-specific B cells target polymorphic, conformational epitopes in VAR2CSA
title_short Human pregnancy-associated malaria-specific B cells target polymorphic, conformational epitopes in VAR2CSA
title_sort human pregnancy-associated malaria-specific b cells target polymorphic, conformational epitopes in var2csa
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2779471/
https://www.ncbi.nlm.nih.gov/pubmed/17176260
http://dx.doi.org/10.1111/j.1365-2958.2006.05503.x
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