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

Sci Rep. 2017 Jun 14;7(1):3472. doi: 10.1038/s41598-017-03042-y.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Epitope Mapping* / methods
  • Epitopes, T-Lymphocyte / chemistry
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Histocompatibility Antigens Class II / immunology
  • Immunity, Cellular*
  • Kinetics
  • Mice
  • Mice, Inbred C57BL
  • Murine pneumonia virus / immunology*
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / virology

Substances

  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class II