In 2018, the World Health Organisation listed influenza pandemics as one of the top threats to global health. Influenza pandemics occur as a result of the emergence of antigenically distinct strains, which arise due to genomic re-assortment or through the acquisition of mutations. Despite Influenza having a high mutation rate, amino acid positions 265-273 of the Influenza A virus (IAV) nucleoprotein (NP) is a conserved immunodominant epitope presented by the Human Leukocyte Antigen (HLA) A*03:01. We investigated the breadth of CD8+ T cell response towards this epitope and identified cross-reactive responses to a novel Influenza B virus (IBV) epitope.
We investigated the level of cross-reactivity of responding CD8+ cells by stimulating T cells from donors expressing HLA-A*03:01 with the FluA and FluB epitopes derived from the NP protein. We also determined the crystal structure of the HLA-A*03:01 in complex with both FluA and FluB epitopes, and provided the molecular basis for T cell crossreactivity. This study contributes unprecedented cross-reactivity between two conserved epitopes derived from Influenza A and B strains, identified a new FluB epitope, and is a key finding for the design of universal vaccines.