Poster Presentation 14th Lorne Infection and Immunity 2024

The exploration of HLA-B*18:01 influenza A derived peptides identified from lung infected cells  (#161)

Samuel Liwei Leong 1 , Emma Grant 1 , Lawton Murdolo 1 , Stephanie Gras 1
  1. La Trobe University, South Morang, VICTORIA, Australia

The influenza virus is responsible for seasonal flu epidemics that account for approximately 600,000 deaths worldwide. In addition, influenza pandemics in the past have caused more than 50 million deaths. CD8+ T cells are known to be critical in the control and clearance of viral infections and could be an attractive target for future vaccines. CD8+ T cells generally recognise peptides that are derived from internal influenza proteins that are less likely to be affected by antigenic drift. However, for CD8+ T cells to recognise immunogenic targets, peptides must be presented by the Human Leukocyte Antigen (HLA) molecules. As HLA molecules are highly polymorphic this poses a significant hurdle for global vaccine design. Thus, it is critical to identify and characterise specific new epitopes for highly prevalent HLA molecules in the global population.


Here, we assessed the immunogenicity of six newly identified influenza-derived peptides from Nicholas et al. (2022) that were predicted to bind to the prevalent HLA-B*18:01 molecule (2.3% of global population). Using CD8+ T cell activation assays, we showed that 3/6 of the novel peptides were immunogenic in several HLA-B*18:01+ individuals, and tetramer staining confirmed their HLA-B*18:01 restriction. We subsequently compared these CD8+ T cell responses to those against the previously identified highly immunogenic HLA-B*18:01-restricted NP219 peptide. We saw an immunodominance hierarchy towards these peptides, with responses against the NP219 peptide being the strongest, followed by responses towards TEV8, EEI9 and QEI8 by tetramer staining and intracellular cytokine staining assays. Finally, we dissected, the first TCR repertoires specific for any pathogen derived peptides presented by HLA-B*18:01 and revealed a private and restricted repertoire for each of the four epitopes. Overall, we confirmed the immunogenicity and HLA-B*18:01 restriction of three new influenza-derived CD8+ T cell epitopes and showed that immune responses towards the known immunogenic NP219 peptide are higher, indicating its potential as a vaccine candidate for HLA-B*18:01+ individuals.