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

Vandersarren, L; Bosteels, C; Vanheerswynghels, M; Moon, JJ; Easton, AJ; Van Isterdael, G; Janssens, S; ... Van Helden, MJ; + view all (2017) Epitope mapping and kinetics of CD4 T cell immunity to pneumonia virus of mice in the C57BL/6 strain. Scientific Reports , 7 (1) , Article 3472. 10.1038/s41598-017-03042-y. Green open access

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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-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.

Type: Article
Title: Epitope mapping and kinetics of CD4 T cell immunity to pneumonia virus of mice in the C57BL/6 strain
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41598-017-03042-y
Publisher version: https://doi.org/10.1038/s41598-017-03042-y
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Lymphocyte activation, Viral infection
URI: https://discovery.ucl.ac.uk/id/eprint/10049241
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