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Epitope mapping and kinetics of CD4 T cell immunity to pneumonia virus of mice in the C57BL/6 strain
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 too...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471230/ https://www.ncbi.nlm.nih.gov/pubmed/28615708 http://dx.doi.org/10.1038/s41598-017-03042-y |
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author | Vandersarren, Lana Bosteels, Cedric Vanheerswynghels, Manon Moon, James J. Easton, Andrew J. Van Isterdael, Gert Janssens, Sophie Lambrecht, Bart N. van Helden, Mary J. |
author_facet | Vandersarren, Lana Bosteels, Cedric Vanheerswynghels, Manon Moon, James J. Easton, Andrew J. Van Isterdael, Gert Janssens, Sophie Lambrecht, Bart N. van Helden, Mary J. |
author_sort | Vandersarren, Lana |
collection | PubMed |
description | 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-IA(b)-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 (M(37–47)). Using this newly identified MHCII-restricted M(37–47) epitope and a previously described MHCI-restricted N(339–347) 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 | Online Article Text |
id | pubmed-5471230 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-54712302017-06-19 Epitope mapping and kinetics of CD4 T cell immunity to pneumonia virus of mice in the C57BL/6 strain Vandersarren, Lana Bosteels, Cedric Vanheerswynghels, Manon Moon, James J. Easton, Andrew J. Van Isterdael, Gert Janssens, Sophie Lambrecht, Bart N. van Helden, Mary J. Sci Rep Article 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-IA(b)-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 (M(37–47)). Using this newly identified MHCII-restricted M(37–47) epitope and a previously described MHCI-restricted N(339–347) 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. Nature Publishing Group UK 2017-06-14 /pmc/articles/PMC5471230/ /pubmed/28615708 http://dx.doi.org/10.1038/s41598-017-03042-y Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Vandersarren, Lana Bosteels, Cedric Vanheerswynghels, Manon Moon, James J. Easton, Andrew J. Van Isterdael, Gert Janssens, Sophie Lambrecht, Bart N. van Helden, Mary J. Epitope mapping and kinetics of CD4 T cell immunity to pneumonia virus of mice in the C57BL/6 strain |
title | 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_short | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471230/ https://www.ncbi.nlm.nih.gov/pubmed/28615708 http://dx.doi.org/10.1038/s41598-017-03042-y |
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