A Novel H-2d Epitope for Influenza A Polymerase Acidic Protein

Understanding the complexity of the T-cell epitope hierarchy in humans through mouse models can be difficult. In particular, using only one murine strain, the C57BL/6 mouse, to investigate the immune response to influenza virus infection limits our understanding. In the present study, by immunizing C57BL/6 mice with an adenoviral vector encoding the polymerase acidic (AdIiPA) protein of influenza A virus, we were able to induce a high number of PA-specific T cells. However, upon challenge, these cells were only partly protective. When instead immunizing BALB/c mice with AdIiPA, we found that the immunized mice were fully protected against challenge. We found that this protection was dependent on CD8 T cells, and we identified a novel H-2D(d)-restricted epitope, PA33. These findings provide a new tool for researchers to study PA-specific immunity in mice with an H-2(d) haplotype. Additionally, our findings underscore the importance of critically evaluating important limitations of using a single inbred mouse strain in vaccine studies.

Automated summary

Understanding the complexity of T-cell epitope hierarchy in humans using mouse models is challenging. Investigating immune response to influenza virus infection in only one mouse strain, C57BL/6, limits our understanding. In this study, immunization with an adenoviral vector encoding influenza A virus polymerase acidic (AdIiPA) protein induced a high number of PA-specific T cells in C57BL/6 mice but provided only partial protection upon challenge. Immunization of BALB/c mice with AdIiPA, however, resulted in full protection, dependent on CD8 T cells, and identified a novel H-2D(d)-restricted epitope (PA33). These findings offer a new tool to study PA-specific immunity in mice with an H-2(d) haplotype, and highlight the importance of evaluating limitations of using a single mouse strain in vaccine studies.