Poster Presentation Lorne Infection and Immunity 2022

CD8+ T cell cross-reactivity towards conserved influenza A and B epitopes (#154)

Andrea T Nguyen 1 2 , Hiu Ming Peter Lau 2 , Hannah Sloane 1 2 , Dhilshan Jayasinghe 1 2 , Nicole A Mifsud 2 , Dimitra SM Chatzileontiadou 1 2 , Christopher Szeto 1 2 , Stephanie Gras 1 2 , Emma Grant 1 2
  1. Infection and Immunity Program, 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

Influenza A, B and C viruses (IAV, IBV and ICV respectively) circulate globally, infecting humans and causing widespread morbidity and mortality. IAV-NP265 is a known HLA-A*03:01-restricted immunodominant epitope, albeit not fully characterised. We identified novel IBV and ICV homologue IAV-NP265 peptides and assessed their immunogenicity, and the presence of cross-reactive CD8+ T cells able to recognise peptides from different influenza virus types. Our study further characterised the CD8+ T cell response to IAV-NP265, and of the newly identified IBV-NP323 and ICV-NP270. We provided evidence of T cell cross-reactivity between those epitopes derived from different influenza types, and its molecular basis by solving the crystal structures of IAV-NP265 and IBV-NP323 peptides in complex with HLA-A*03:01. Altogether, our study provides evidence behind T cell cross-reactivity across a universally conserved epitope from different types of influenza viruses, which has an important impact for vaccine consideration.