Differential epitope recognition in the immunodominant staphylococcal antigen A of Staphylococcus aureus by mouse versus human IgG antibodies

Abstract The immunodominant staphylococcal antigen A (IsaA) is a potential target for active or passive immunization against the important human pathogen Staphylococcus aureus. Consistent with this view, monoclonal antibodies against IsaA were previously shown to be protective against S. aureus infe...

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Autores principales:	Dennis G. A. M. Koedijk, Francisco Romero Pastrana, Hedzer Hoekstra, Sanne van den Berg, Jaap Willem Back, Carolien Kerstholt, Rianne C. Prins, Irma A. J. M. Bakker-Woudenberg, Jan Maarten van Dijl, Girbe Buist
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b9edba205bb84320857cd7a1bed7f1dd
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spelling	oai:doaj.org-article:b9edba205bb84320857cd7a1bed7f1dd2021-12-02T12:32:25ZDifferential epitope recognition in the immunodominant staphylococcal antigen A of Staphylococcus aureus by mouse versus human IgG antibodies10.1038/s41598-017-08182-92045-2322https://doaj.org/article/b9edba205bb84320857cd7a1bed7f1dd2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08182-9https://doaj.org/toc/2045-2322Abstract The immunodominant staphylococcal antigen A (IsaA) is a potential target for active or passive immunization against the important human pathogen Staphylococcus aureus. Consistent with this view, monoclonal antibodies against IsaA were previously shown to be protective against S. aureus infections in mouse models. Further, patients with the genetic blistering disease epidermolysis bullosa (EB) displayed high IsaA-specific IgG levels that could potentially be protective. Yet, mice actively immunized with IsaA were not protected against S. aureus infection. The present study was aimed at explaining these differences in IsaA-specific immune responses. By epitope mapping, we show that the protective human monoclonal antibody (humAb) 1D9 recognizes a conserved 62-residue N-terminal domain of IsaA. The same region of IsaA is recognized by IgGs in EB patient sera. Further, we show by immunofluorescence microscopy that this N-terminal IsaA domain is exposed on the S. aureus cell surface. In contrast to the humAb 1D9 and IgGs from EB patients, the non-protective IgGs from mice immunized with IsaA were shown to predominantly bind the C-terminal domain of IsaA. Altogether, these observations focus attention on the N-terminal region of IsaA as a potential target for future immunization against S. aureus.Dennis G. A. M. KoedijkFrancisco Romero PastranaHedzer HoekstraSanne van den BergJaap Willem BackCarolien KerstholtRianne C. PrinsIrma A. J. M. Bakker-WoudenbergJan Maarten van DijlGirbe BuistNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Dennis G. A. M. Koedijk Francisco Romero Pastrana Hedzer Hoekstra Sanne van den Berg Jaap Willem Back Carolien Kerstholt Rianne C. Prins Irma A. J. M. Bakker-Woudenberg Jan Maarten van Dijl Girbe Buist Differential epitope recognition in the immunodominant staphylococcal antigen A of Staphylococcus aureus by mouse versus human IgG antibodies
description	Abstract The immunodominant staphylococcal antigen A (IsaA) is a potential target for active or passive immunization against the important human pathogen Staphylococcus aureus. Consistent with this view, monoclonal antibodies against IsaA were previously shown to be protective against S. aureus infections in mouse models. Further, patients with the genetic blistering disease epidermolysis bullosa (EB) displayed high IsaA-specific IgG levels that could potentially be protective. Yet, mice actively immunized with IsaA were not protected against S. aureus infection. The present study was aimed at explaining these differences in IsaA-specific immune responses. By epitope mapping, we show that the protective human monoclonal antibody (humAb) 1D9 recognizes a conserved 62-residue N-terminal domain of IsaA. The same region of IsaA is recognized by IgGs in EB patient sera. Further, we show by immunofluorescence microscopy that this N-terminal IsaA domain is exposed on the S. aureus cell surface. In contrast to the humAb 1D9 and IgGs from EB patients, the non-protective IgGs from mice immunized with IsaA were shown to predominantly bind the C-terminal domain of IsaA. Altogether, these observations focus attention on the N-terminal region of IsaA as a potential target for future immunization against S. aureus.
format	article
author	Dennis G. A. M. Koedijk Francisco Romero Pastrana Hedzer Hoekstra Sanne van den Berg Jaap Willem Back Carolien Kerstholt Rianne C. Prins Irma A. J. M. Bakker-Woudenberg Jan Maarten van Dijl Girbe Buist
author_facet	Dennis G. A. M. Koedijk Francisco Romero Pastrana Hedzer Hoekstra Sanne van den Berg Jaap Willem Back Carolien Kerstholt Rianne C. Prins Irma A. J. M. Bakker-Woudenberg Jan Maarten van Dijl Girbe Buist
author_sort	Dennis G. A. M. Koedijk
title	Differential epitope recognition in the immunodominant staphylococcal antigen A of Staphylococcus aureus by mouse versus human IgG antibodies
title_short	Differential epitope recognition in the immunodominant staphylococcal antigen A of Staphylococcus aureus by mouse versus human IgG antibodies
title_full	Differential epitope recognition in the immunodominant staphylococcal antigen A of Staphylococcus aureus by mouse versus human IgG antibodies
title_fullStr	Differential epitope recognition in the immunodominant staphylococcal antigen A of Staphylococcus aureus by mouse versus human IgG antibodies
title_full_unstemmed	Differential epitope recognition in the immunodominant staphylococcal antigen A of Staphylococcus aureus by mouse versus human IgG antibodies
title_sort	differential epitope recognition in the immunodominant staphylococcal antigen a of staphylococcus aureus by mouse versus human igg antibodies
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b9edba205bb84320857cd7a1bed7f1dd
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Differential epitope recognition in the immunodominant staphylococcal antigen A of Staphylococcus aureus by mouse versus human IgG antibodies

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