Cd4+T Cell Recognition Of Haemagglutinin Epitope Across Influenza Strains

Abstract 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. The resulting strains have different antigenic make-ups and implicate the ability of the immune system to respond quickly following infection. Particular HLA class II allomorphs including HLA-DRB1*07:01 have been linked with the occurrence of severe influenza infections and non-response to the influenza vaccine. However, other allomorphs such as HLA-DRB1*11:01 have been shown to be protective in viral diseases such as HIV and HCV, and might be important for influenza infection. The mechanism surrounding these associations of influenza infection and HLA class II molecules expression is unclear. As some individuals expressing particular HLA allomorphs are at a greater risk of developing severe influenza infection, further investigation into the mechanism of this association is warranted. Through stimulating T cells from donors expressing HLA-DRB1*11:01 or HLA-DRB1*07:01 with an influenza epitope (HA) derived from pandemic and epidemic influenza strains, we determined the level of cross-reactivity, phenotype and polyfunctionality of the responding CD4+ specific T cells. We have compared different allomorphs and provide the first insight into the molecular basis of influenza epitope recognition by different HLA class II allomorphs, and its functional impact.