Dr
Emma Grant
(The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Biomedicine Discovery Institute, Monash University )
Newly-emerged and vaccine-mismatched influenza A viruses (IAVs) result in a rapid global spread of the virus due to minimal antibody-mediated immunity. In that case, established CD8+ T-cells can reduce disease severity. However, as mutations occur sporadically within immunogenic IAV-derived T-cell peptides, understanding of T-cell receptor (TCRab) cross-reactivity towards IAV variants is needed for a vaccine design. We investigated TCRab cross-strain recognition across IAV variants within two immunodominant human IAV-specific CD8+ T-cell epitopes, HLA-B37:01-restricted NP338-346 (B37-NP338) and HLA-A01:01-restricted NP44-52 (A1-NP44). We found high abundance of cross-reactive TCRab clonotypes recognizing distinct IAV variants. Structures of the wild-type and variant peptides presented revealed preserved conformation of the bound peptides. Structures of a cross-reactive TCR-HLA-B37-NP338 complex suggest that molecular mimicry underpins TCR cross-reactivity towards the mutated variants. Overall, cross-reactive CD8+ T-cell responses, underpinned by molecular mimicry, facilitate recognition of distinct IAV variants, thus CD8+ T-cell targeted vaccines could provide protection across different IAV strains.
Dr
Emma Grant
(The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Biomedicine Discovery Institute, Monash University )
Dr
Tracy Josephs
(Monash University)
Dr
Liyen Loh
(The University of Melbourne at the Peter Doherty Institute for Infection and Immunity)
Dr
E. Bridie Clemens
(The University of Melbourne at the Peter Doherty Institute for Infection and Immunity)
Ms
Sneha Sant
(The University of Melbourne at the Peter Doherty Institute for Infection and Immunity)
Dr
Mandvi Bharadwaj
(The University of Melbourne at the Peter Doherty Institute for Infection and Immunity)
Prof.
Weisan Chen
(3La Trobe Institute of Molecular Science, La Trobe University)
Prof.
Jamie Rossjohn
(Biomedicine Discovery Institute, Monash University. Institute of Infection and Immunity, Cardiff University. ARC Centre of Excellence in Advanced Molecular Imaging, Monash University. )
Prof.
Katherine Kedzierska
(The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity)
Dr
Stephanie Gras
(Biomedicine Discovery Institute, Monash University. ARC Centre of Excellence in Advanced Molecular Imaging, Monash University. )
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