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- Title
Homologous peptides derived from influenza A, B and C viruses induce variable CD8<sup>+</sup> T cell responses with cross‐reactive potential.
- Authors
Nguyen, Andrea T; Lau, Hiu Ming Peter; Sloane, Hannah; Jayasinghe, Dhilshan; Mifsud, Nicole A; Chatzileontiadou, Demetra SM; Grant, Emma J; Szeto, Christopher; Gras, Stephanie
- 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.
- Subjects
T cells; HISTOCOMPATIBILITY antigens; T cell receptors; PEPTIDES; INFLUENZA; X-ray crystallography
- Publication
Clinical & Translational Immunology, 2022, Vol 11, Issue 10, p1
- ISSN
2050-0068
- Publication type
Article
- DOI
10.1002/cti2.1422