Epitope mapping and kinetics of CD4 T cell immunity to pneumonia virus of mice in the C57BL/6 strain

Abstract Pneumonia virus of mice (PVM) infection has been widely used as a rodent model to study the closely related human respiratory syncytial virus (hRSV). While T cells are indispensable for viral clearance, they also contribute to immunopathology. To gain more insight into mechanistic details,...

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Autores principales: Lana Vandersarren, Cedric Bosteels, Manon Vanheerswynghels, James J. Moon, Andrew J. Easton, Gert Van Isterdael, Sophie Janssens, Bart N. Lambrecht, Mary J. van Helden
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:ed7366480c22478683becde7e2833f4c2021-12-02T16:06:50ZEpitope mapping and kinetics of CD4 T cell immunity to pneumonia virus of mice in the C57BL/6 strain10.1038/s41598-017-03042-y2045-2322https://doaj.org/article/ed7366480c22478683becde7e2833f4c2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03042-yhttps://doaj.org/toc/2045-2322Abstract Pneumonia virus of mice (PVM) infection has been widely used as a rodent model to study the closely related human respiratory syncytial virus (hRSV). While T cells are indispensable for viral clearance, they also contribute to immunopathology. To gain more insight into mechanistic details, novel tools are needed that allow to study virus-specific T cells in C57BL/6 mice as the majority of transgenic mice are only available on this background. While PVM-specific CD8 T cell epitopes were recently described, so far no PVM-specific CD4 T cell epitopes have been identified within the C57BL/6 strain. Therefore, we set out to map H2-IAb-restricted epitopes along the PVM proteome. By means of in silico prediction and subsequent functional validation, we were able to identify a MHCII-restricted CD4 T cell epitope, corresponding to amino acids 37–47 in the PVM matrix protein (M37–47). Using this newly identified MHCII-restricted M37–47 epitope and a previously described MHCI-restricted N339–347 epitope, we generated peptide-loaded MHCII and MHCI tetramers and characterized the dynamics of virus-specific CD4 and CD8 T cell responses in vivo. The findings of this study can provide a basis for detailed investigation of T cell-mediated immune responses to PVM in a variety of genetically modified C57BL/6 mice.Lana VandersarrenCedric BosteelsManon VanheerswynghelsJames J. MoonAndrew J. EastonGert Van IsterdaelSophie JanssensBart N. LambrechtMary J. van HeldenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Lana Vandersarren
Cedric Bosteels
Manon Vanheerswynghels
James J. Moon
Andrew J. Easton
Gert Van Isterdael
Sophie Janssens
Bart N. Lambrecht
Mary J. van Helden
Epitope mapping and kinetics of CD4 T cell immunity to pneumonia virus of mice in the C57BL/6 strain
description Abstract Pneumonia virus of mice (PVM) infection has been widely used as a rodent model to study the closely related human respiratory syncytial virus (hRSV). While T cells are indispensable for viral clearance, they also contribute to immunopathology. To gain more insight into mechanistic details, novel tools are needed that allow to study virus-specific T cells in C57BL/6 mice as the majority of transgenic mice are only available on this background. While PVM-specific CD8 T cell epitopes were recently described, so far no PVM-specific CD4 T cell epitopes have been identified within the C57BL/6 strain. Therefore, we set out to map H2-IAb-restricted epitopes along the PVM proteome. By means of in silico prediction and subsequent functional validation, we were able to identify a MHCII-restricted CD4 T cell epitope, corresponding to amino acids 37–47 in the PVM matrix protein (M37–47). Using this newly identified MHCII-restricted M37–47 epitope and a previously described MHCI-restricted N339–347 epitope, we generated peptide-loaded MHCII and MHCI tetramers and characterized the dynamics of virus-specific CD4 and CD8 T cell responses in vivo. The findings of this study can provide a basis for detailed investigation of T cell-mediated immune responses to PVM in a variety of genetically modified C57BL/6 mice.
format article
author Lana Vandersarren
Cedric Bosteels
Manon Vanheerswynghels
James J. Moon
Andrew J. Easton
Gert Van Isterdael
Sophie Janssens
Bart N. Lambrecht
Mary J. van Helden
author_facet Lana Vandersarren
Cedric Bosteels
Manon Vanheerswynghels
James J. Moon
Andrew J. Easton
Gert Van Isterdael
Sophie Janssens
Bart N. Lambrecht
Mary J. van Helden
author_sort Lana Vandersarren
title Epitope mapping and kinetics of CD4 T cell immunity to pneumonia virus of mice in the C57BL/6 strain
title_short Epitope mapping and kinetics of CD4 T cell immunity to pneumonia virus of mice in the C57BL/6 strain
title_full Epitope mapping and kinetics of CD4 T cell immunity to pneumonia virus of mice in the C57BL/6 strain
title_fullStr Epitope mapping and kinetics of CD4 T cell immunity to pneumonia virus of mice in the C57BL/6 strain
title_full_unstemmed Epitope mapping and kinetics of CD4 T cell immunity to pneumonia virus of mice in the C57BL/6 strain
title_sort epitope mapping and kinetics of cd4 t cell immunity to pneumonia virus of mice in the c57bl/6 strain
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/ed7366480c22478683becde7e2833f4c
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