Development of a Mouse Model to Explore CD4 T Cell Specificity, Phenotype, and Recruitment to the Lung after Influenza B Infection
Ajitanuj Rattan,
Chantelle L. White,
Sean Nelson,
Max Eismann,
Herbey Padilla-Quirarte,
Maryah A. Glover,
Thamotharampillai Dileepan,
Bindumadhav M. Marathe,
Elena A. Govorkova,
Richard J. Webby,
Katherine A. Richards,
Andrea J. Sant
Affiliations
Ajitanuj Rattan
David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA
Chantelle L. White
David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA
Sean Nelson
David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA
Max Eismann
David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA
Herbey Padilla-Quirarte
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA
Maryah A. Glover
David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA
Thamotharampillai Dileepan
Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA
Bindumadhav M. Marathe
Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Elena A. Govorkova
Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Richard J. Webby
Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Katherine A. Richards
David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA
Andrea J. Sant
David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA
The adaptive T cell response to influenza B virus is understudied, relative to influenza A virus, for which there has been considerable attention and progress for many decades. Here, we have developed and utilized the C57BL/6 mouse model of intranasal infection with influenza B (B/Brisbane/60/2008) virus and, using an iterative peptide discovery strategy, have identified a series of robustly elicited individual CD4 T cell peptide specificities. The CD4 T cell repertoire encompassed at least eleven major epitopes distributed across hemagglutinin, nucleoprotein, neuraminidase, and non-structural protein 1 and are readily detected in the draining lymph node, spleen, and lung. Within the lung, the CD4 T cells are localized to both lung vasculature and tissue but are highly enriched in the lung tissue after infection. When studied by flow cytometry and MHC class II: peptide tetramers, CD4 T cells express prototypical markers of tissue residency including CD69, CD103, and high surface levels of CD11a. Collectively, our studies will enable more sophisticated analyses of influenza B virus infection, where the fate and function of the influenza B-specific CD4 T cells elicited by infection and vaccination can be studied as well as the impact of anti-viral reagents and candidate vaccines on the abundance, functionality, and localization of the elicited CD4 T cells.
