Identification and characterization of CD8 T cell epitopes within an influenza B virus murine model of infection

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.