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Payton Kahl Thesis Revisions10.02 MB
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Thesis
Identification and characterization of CD8 T cell epitopes within an influenza B virus murine model of infection
University of Iowa
Master of Science (MS), University of Iowa
Autumn 2025
DOI: 10.25820/etd.008216
Abstract
Influenza virus infections remain a significant cause of illness and death worldwide. Although both influenza A (IAV) and influenza B (IBV) viruses cause annual outbreaks, IBV causes nearly half of the pediatric influenza virus-related deaths and remains understudied due to the lack of suitable research tools. In this thesis, I established a reliable mouse model for both lineages of IBV (i.e. Victoria and Yamagata). After successful model development, I was able to examine the immune response in C57BL/6 mice after sublethal infection with each IBV lineage. My findings demonstrate that IBV increases the antigen-experienced T cell populations in the lungs after infection. To better understand the targets of these T cells, I utilized an in silico method of epitope discovery that uses computer learning software to identify potential T cell targets within the IBV proteins hemagglutanin (HA) and nucleoprotein (NP). I additionally utilized an overlapping peptide array for these proteins in order to determine any epitopes/peptide targets that may have been missed by the computer-based approach. Potential peptide targets were then screened for T cell reactivity during IBV infection. My initial analyses identified 3 previously unreported CD8 T cell epitopes within the NP protein. Continued analysis identified 3 additional CD8 T cell epitopes (2 within the HA protein and 1 within the NP protein) capable of inducing a CD8 T cell response. Utilizing one of the new CD8 T cell epitopes, I then quantified kinetics and location of these epitope-specific T cells throughout infection. This study allows for further investigation into how these IBV-specific T cell responses may contribute to protection and will assist in the development of next-generation vaccines to influenza B virus that are able to elicit strong, durable T cell responses.
Details
- Title: Subtitle
- Identification and characterization of CD8 T cell epitopes within an influenza B virus murine model of infection
- Creators
- Payton Justice Kahl
- Contributors
- Kevin Legge (Advisor)John Harty (Committee Member)Vladimir Badovinac (Committee Member)Josalyn Cho (Committee Member)
- Resource Type
- Thesis
- Degree Awarded
- Master of Science (MS), University of Iowa
- Degree in
- Pathology
- Date degree season
- Autumn 2025
- DOI
- 10.25820/etd.008216
- Publisher
- University of Iowa
- Number of pages
- ix, 96 pages
- Copyright
- Copyright 2025 Payton Justice Kahl
- Language
- English
- Date submitted
- 12/08/2025
- Description illustrations
- illustrations, graphs, tables
- Description bibliographic
- Includes bibliographical references (pages 88-96).
- Public Abstract (ETD)
- Influenza virus infections continue to cause considerable disease worldwide. While both influenza A (IAV) and influenza B (IBV) viruses drive seasonal epidemics, IBV accounts for nearly half of influenza-associated pediatric deaths and remains understudied compared to IAV due to limited experimental models. T cells are known to be a critical factor in controlling IAV infections. Therefore, in this thesis, I developed a mouse model of IBV in order to evaluate T cell immunity during IBV. Following sublethal infection, we observed increases numbers of T cells within the lungs. To determine if these T cell responses were specific for IBV, I utilized a computer based learning software and overlapping peptide libraries to discover peptides within IBV hemagglutinin (HA) and nucleoprotein (NP) that CD8 T cells could recognize. The initial analysis revealed 3 previously undescribed CD8 T cell epitopes in NP. Continued studies showed 3 additional peptides (2 in HA and 1 in NP) also capable of inducing a CD8 T cell response. Taking one of the peptides that the CD8 T cell were specific for, I was able to quantify an IBV-specific CD8 T cell response in different tissues across the course of infection. Ongoing characterization of this IBV-specific T cell response has the potential to allow a better understanding of the contribution of CD8 T cells in the control and protection against IBV.
- Academic Unit
- Pathology
- Record Identifier
- 9985135049402771
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