title: Identification of a CD4 T cell epitope in the pneumonia virus of mice glycoprotein and characterization of its role in protective immunity.
abstract: Pneumonia virus of mice (PVM) causes bronchiolitis and pneumonia in mice. Infection is associated with high levels of viral replication in the lungs and results in the functional inactivation of pulmonary virus-specific CD8 T cells. Due to its similarity to severe human respiratory syncytial virus (RSV) infection, PVM infection in mice has been proposed as an alternative RSV model. Here, we have delineated the minimal requirements for protective T cell immunity in the PVM model. Immunization with a CD8 T cell epitope from the PVM phosphoprotein P, combined with the ovalbumin (OVA) CD4 T cell epitope, did not confer protective immunity against lethal PVM challenge, suggesting a possible role of cognate CD4 T cell immunity. To determine the role of PVM-specific CD4 T cell responses, we mapped a PVM CD4 T cell epitope in the glycoprotein G, using a panel of overlapping peptides. Although immunization with this epitope provided some protection, solid protective immunity was only observed after immunization with a combination of the PVM-specific CD4 and CD8 T cell epitopes. Analysis of post-challenge T cell responses in immunized mice indicated that G-specific pulmonary CD4 T cells displayed a mixed Th1/Th2 phenotype, which was characterized by the presence of both IL-5 and IFN-gamma secreting cells, in the absence of overt pathology.
authors.affiliation: Division of Immunology, Faculty of Veterinary Science, University of Utrecht, Utrecht, The Netherlands.
authors.forename: Erwin A W
authors.initials: EA
authors.lastname: Claassen
authors.forename: Grada M
authors.initials: GM
authors.lastname: van Bleek
authors.forename: Zuzana S
authors.initials: ZS
authors.lastname: Rychnavska
authors.forename: Raoul J
authors.initials: RJ
authors.lastname: de Groot
authors.forename: Evert J
authors.initials: EJ
authors.lastname: Hensen
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Tijhaar
authors.forename: Willem
authors.initials: W
authors.lastname: van Eden
authors.forename: Robbert G
authors.initials: RG
authors.lastname: van der Most
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D029122:Murine pneumonia virus / Q000276:immunology*; D018186:Pneumovirus Infections / Q000276:immunology*; D016019:Survival Analysis; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D015848:Interleukin-5; D014759:Viral Envelope Proteins; C092203:glycoprotein G, Pneumonia virus of mice; D007371:Interferon-gamma