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

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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 encom-passed at least eleven major epitopes distributed across hemagglutinin, nucleoprotein, neuramini-dase, 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.

Original languageEnglish (US)
Article number251
JournalPathogens
Volume11
Issue number2
DOIs
StatePublished - Feb 2022

Bibliographical note

Funding Information:
Funding: This project has been funded partially with Federal funds from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services, under CEIRS Contract No. HHSN272201400005C to AJS. This project has been funded in part by Grant 3R01AI114554-04 and Grant 12636631. These studies have also been supported in part through NIAID, NIH, Department of Health and Human Services, under Contract No. 75N93021C00018 (NIAID Centers of Excellence for Influenza Research and Response, CEIRR). St. Jude Children’s Research Hospital has been funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract 75N93021C00016 and by ALSAC. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • CD4 T cell
  • Immune response
  • Influenza virus

PubMed: MeSH publication types

  • Journal Article

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