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

• Published in: Scientific reports Vol. 7; no. 1; pp. 3472 - 10
• Main Authors: Vandersarren, Lana, Bosteels, Cedric, Vanheerswynghels, Manon, Moon, James J., Easton, Andrew J., Van Isterdael, Gert, Janssens, Sophie, Lambrecht, Bart N., van Helden, Mary J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.06.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/106; 13/21; 13/31; 38; 38/90; 631/250/255/2514; 64/60; 692/420/2780/2152/1566/1618; Amino Acid Sequence; Amino acids; Animals; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cells, Cultured; Epitope mapping; Epitope Mapping - methods; Epitopes, T-Lymphocyte - chemistry; Epitopes, T-Lymphocyte - immunology; Female; Histocompatibility Antigens Class II - immunology; Humanities and Social Sciences; Immune clearance; Immune response (cell-mediated); Immunity, Cellular; Kinetics; Lymphocytes; Lymphocytes T; Matrix protein; Mice; Mice, Inbred C57BL; multidisciplinary; Murine pneumonia virus - immunology; Pneumonia; Pneumonia, Viral - immunology; Pneumonia, Viral - virology; Proteomes; Respiratory syncytial virus; Science; Science (multidisciplinary); T cell receptors; Transgenic mice
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-03042-y

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.