Poster Presentation 14th Lorne Infection and Immunity 2024

CD4+ T cell recognition of Haemagglutinin epitopes across different influenza strains (#141)

Hannah Sloane 1 2 , Dhilshan Jayasinghe 1 2 , Christopher Szeto 1 2 , Andrea Nguyen 1 2 , Stephanie Gras 1 2 , Emma J Grant 1 2
  1. Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, 3086, Victoria, Australia
  2. Department of Biochemistry and Molecular Biology, Monash University, Clayton 3800, Victoria, Australia

The ongoing SARS-Cov2 pandemic is a modern-day reminder of the impact that novel viral strains can have on a population without pre-existing immunity. The influenza A virus (IAV) has caused five pandemics in the last 150 years and is particularly prone to mutations in the surface glycoprotein haemagglutinin (HA) which is the primary target of the CD4+ T cell and antibody responses.


CD4+ T cells recognise peptide presented by human leukocyte antigen class II (HLA-II) molecules with their T cell receptor (TCR). Although the pHLA-II-TCR interaction is extremely specific, it may cross-recognise similar peptides leading to a cross-reactive response, and providing broad protection against different IAV strains. The ability of CD4+ T cells to cross-react with variants of a HA peptide from different IAV strains, especially those not in circulation, is not well understood. Furthermore, individuals expressing certain HLA-II molecules are known to be more susceptible to severe viral infections. In the context of IAV, HLA-DRB1*07:01 has been associated with poor response to the influenza vaccine whereas HLA-DRB1*11:01 has been associated with protection from viruses such as HIV and HCV. Investigation into the molecular basis underlying this association is warranted.


Using intracellular cytokine staining and HLA-II tetramer staining, we found that HLA-DRB1*11:01+ individuals have more cross-reactive responses towards HA peptide derived from different IAV strains than HLA-DRB1*07:01+ individuals, and that the cross-reacting CD4+ T cells generally have lower polyfunctionality than specific CD4+ T cells. Moreover, we provide the first insight into the molecular and functional basis of IAV epitope presentation by different HLA-II molecules.