tetano
Editor, Senior Moderator
Clin Transl Immunology
. 2022 Oct 19;11(10):e1422.
doi: 10.1002/cti2.1422. eCollection 2022.
Homologous peptides derived from influenza A, B and C viruses induce variable CD8[SUP]+[/SUP] T cell responses with cross-reactive potential
Andrea T Nguyen[SUP] 1 2 [/SUP], Hiu Ming Peter Lau[SUP] 1 [/SUP], Hannah Sloane[SUP] 1 2 [/SUP], Dhilshan Jayasinghe[SUP] 1 2 [/SUP], Nicole A Mifsud[SUP] 1 [/SUP], Demetra Sm Chatzileontiadou[SUP] 1 2 [/SUP], Emma J Grant[SUP] 1 2 [/SUP], Christopher Szeto[SUP] 1 2 [/SUP], Stephanie Gras[SUP] 1 2 [/SUP]
Affiliations
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, NP[SUB]265-273,[/SUB] 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[SUP]+[/SUP] T cell response (intracellular cytokine staining) towards NP[SUB]265-IAV[/SUB] and described the T cell receptor (TCR) repertoire used to recognise this immunodominant epitope. We next assessed the immunogenicity of NP[SUB]265-IAV[/SUB] homologue peptides from IBV and ICV and the ability of CD8[SUP]+[/SUP] T cells to cross-react towards these homologous peptides. Furthermore, we determined the structures of NP[SUB]265-IAV[/SUB] and NP[SUB]323-IBV[/SUB] peptides in complex with HLA-A*03:01 by X-ray crystallography.
Results: Our study provides a detailed characterisation of the CD8[SUP]+[/SUP] T cell response towards NP[SUB]265-IAV[/SUB] and its IBV and ICV homologues. The data revealed a diverse repertoire for NP[SUB]265-IAV[/SUB] 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.
Keywords: CD8+ T cell; HLA; Influenza; cross‐reactivity; immune response; immunodominant epitope.
. 2022 Oct 19;11(10):e1422.
doi: 10.1002/cti2.1422. eCollection 2022.
Homologous peptides derived from influenza A, B and C viruses induce variable CD8[SUP]+[/SUP] T cell responses with cross-reactive potential
Andrea T Nguyen[SUP] 1 2 [/SUP], Hiu Ming Peter Lau[SUP] 1 [/SUP], Hannah Sloane[SUP] 1 2 [/SUP], Dhilshan Jayasinghe[SUP] 1 2 [/SUP], Nicole A Mifsud[SUP] 1 [/SUP], Demetra Sm Chatzileontiadou[SUP] 1 2 [/SUP], Emma J Grant[SUP] 1 2 [/SUP], Christopher Szeto[SUP] 1 2 [/SUP], Stephanie Gras[SUP] 1 2 [/SUP]
Affiliations
- PMID: 36275878
- PMCID: PMC9581725
- DOI: 10.1002/cti2.1422
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, NP[SUB]265-273,[/SUB] 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[SUP]+[/SUP] T cell response (intracellular cytokine staining) towards NP[SUB]265-IAV[/SUB] and described the T cell receptor (TCR) repertoire used to recognise this immunodominant epitope. We next assessed the immunogenicity of NP[SUB]265-IAV[/SUB] homologue peptides from IBV and ICV and the ability of CD8[SUP]+[/SUP] T cells to cross-react towards these homologous peptides. Furthermore, we determined the structures of NP[SUB]265-IAV[/SUB] and NP[SUB]323-IBV[/SUB] peptides in complex with HLA-A*03:01 by X-ray crystallography.
Results: Our study provides a detailed characterisation of the CD8[SUP]+[/SUP] T cell response towards NP[SUB]265-IAV[/SUB] and its IBV and ICV homologues. The data revealed a diverse repertoire for NP[SUB]265-IAV[/SUB] 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.
Keywords: CD8+ T cell; HLA; Influenza; cross‐reactivity; immune response; immunodominant epitope.