Projects per year
Abstract
Objective: Influenza A, B and C viruses (IAV, IBV and ICV, respectively) circulate globally, infecting humans and causing widespread morbidity and mortality. Here, we investigate the T cell response towards an immunodominant IAV epitope, NP265-273, and its IBV and ICV homologues, presented by HLA-A*03:01 molecule expressed in ~ 4% of the global population (~ 300 million people). Methods: We assessed the magnitude (tetramer staining) and quality of the CD8+ T cell response (intracellular cytokine staining) towards NP265-IAV and described the T cell receptor (TCR) repertoire used to recognise this immunodominant epitope. We next assessed the immunogenicity of NP265-IAV homologue peptides from IBV and ICV and the ability of CD8+ T cells to cross-react towards these homologous peptides. Furthermore, we determined the structures of NP265-IAV and NP323-IBV peptides in complex with HLA-A*03:01 by X-ray crystallography. Results: Our study provides a detailed characterisation of the CD8+ T cell response towards NP265-IAV and its IBV and ICV homologues. The data revealed a diverse repertoire for NP265-IAV that is associated with superior anti-viral protection. Evidence of cross-reactivity between the three different influenza virus strain-derived epitopes was observed, indicating the discovery of a potential vaccination target that is broad enough to cover all three influenza strains. Conclusion: We show that while there is a potential to cross-protect against distinct influenza virus lineages, the T cell response was stronger against the IAV peptide than IBV or ICV, which is an important consideration when choosing targets for future vaccine design.
Original language | English |
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Article number | e1422 |
Number of pages | 17 |
Journal | Clinical & Translational Immunology |
Volume | 11 |
Issue number | 10 |
DOIs | |
Publication status | Published - 2022 |
Keywords
- CD8 T cell
- cross-reactivity
- HLA
- immune response
- immunodominant epitope
- Influenza
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The investigation of an unconventional Human Leukocyte Antigen molecule
Australian Research Council (ARC)
1/01/21 → 1/01/21
Project: Research
Equipment
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Australian Synchrotron
Office of the Vice-Provost (Research and Research Infrastructure)Facility/equipment: Facility
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FlowCore
Andrew Fryga (Manager)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility