tetano
Editor, Senior Moderator
Clin Transl Immunology
. 2026 Oct 13;15(10):e70123.
doi: 10.1002/cti2.70123. eCollection 2026.
Lawton D Murdolo 1 2 , Samuel Liwei Leong 1 2 , Janesha C Maddumage 1 2 , Lloyd D'Orsogna 3 4 , Demetra Sm Chatzileontiadou 1 2 5 , Emma J Grant 1 2 5 , Stephanie Gras 1 2 5
Affiliations Expand
Objectives: Despite the availability of vaccines, influenza viruses still cause substantial morbidity and mortality. This highlights the need for improved vaccines and novel therapeutics. CD8+ T cells recognise conserved viral epitopes and can provide broad protection, making them attractive targets for next-generation vaccine design. A key step in this process is to identify T cell epitopes across influenza viruses. Here, we characterised three homologous influenza Polymerase Basic 1 (PB1)-derived peptides from influenza viruses (PB1-A310, PB1-B310 and PB1-C312, respectively) presented by the common, but understudied, HLA-B*18:01 molecule.
Methods: We used a thermal melt assay and X-ray crystallography to assess the stability and structural features of each peptide. CD8+ T-cell responses were evaluated using intracellular cytokine staining with HLA-B*18:01+ samples.
Results: The structures of HLA-B*18:01 presenting each peptide were solved, including the first structure of HLA-B*18:01 presenting a Gammainfluenzavirus (formerly influenza C virus) derived peptide. PB1-C312 exhibited a higher thermal stability and a different conformation compared to PB1-A310 and PB1-B310. CD8+ T cell responses varied among samples, with PB1-A310 eliciting the strongest activation. Minimal T cell cross-reactivity was observed and was mostly between PB1-A310 and PB1-B310 likely reflecting shared structural features.
Conclusion: These findings further expand knowledge on peptide presentation by the common HLA-B*18:01 molecule, and the limitations on CD8+ T cell cross-recognition of this PB1-derived epitope across influenza lineages. This highlights the importance of more research on cross-lineage T cell cross-reactivity that could inform the design of broadly protective T cell-based vaccines and therapeutics.
Keywords: CD8+ T cells; HLA‐B*18:01; T cell cross‐reactivity; X‐ray crystallography; influenza virus.
. 2026 Oct 13;15(10):e70123.
doi: 10.1002/cti2.70123. eCollection 2026.
Assessing CD8+ T cell cross-reactivity to influenza A, B and C virus-derived peptides presented by HLA-B*18:01
Lawton D Murdolo 1 2 , Samuel Liwei Leong 1 2 , Janesha C Maddumage 1 2 , Lloyd D'Orsogna 3 4 , Demetra Sm Chatzileontiadou 1 2 5 , Emma J Grant 1 2 5 , Stephanie Gras 1 2 5
Affiliations Expand
- PMID: 42871798
- PMCID: PMC13659276
- DOI: 10.1002/cti2.70123
Abstract
Objectives: Despite the availability of vaccines, influenza viruses still cause substantial morbidity and mortality. This highlights the need for improved vaccines and novel therapeutics. CD8+ T cells recognise conserved viral epitopes and can provide broad protection, making them attractive targets for next-generation vaccine design. A key step in this process is to identify T cell epitopes across influenza viruses. Here, we characterised three homologous influenza Polymerase Basic 1 (PB1)-derived peptides from influenza viruses (PB1-A310, PB1-B310 and PB1-C312, respectively) presented by the common, but understudied, HLA-B*18:01 molecule.
Methods: We used a thermal melt assay and X-ray crystallography to assess the stability and structural features of each peptide. CD8+ T-cell responses were evaluated using intracellular cytokine staining with HLA-B*18:01+ samples.
Results: The structures of HLA-B*18:01 presenting each peptide were solved, including the first structure of HLA-B*18:01 presenting a Gammainfluenzavirus (formerly influenza C virus) derived peptide. PB1-C312 exhibited a higher thermal stability and a different conformation compared to PB1-A310 and PB1-B310. CD8+ T cell responses varied among samples, with PB1-A310 eliciting the strongest activation. Minimal T cell cross-reactivity was observed and was mostly between PB1-A310 and PB1-B310 likely reflecting shared structural features.
Conclusion: These findings further expand knowledge on peptide presentation by the common HLA-B*18:01 molecule, and the limitations on CD8+ T cell cross-recognition of this PB1-derived epitope across influenza lineages. This highlights the importance of more research on cross-lineage T cell cross-reactivity that could inform the design of broadly protective T cell-based vaccines and therapeutics.
Keywords: CD8+ T cells; HLA‐B*18:01; T cell cross‐reactivity; X‐ray crystallography; influenza virus.