Characterisation of novel influenza-derived HLA-B*18:01-restricted epitopes.
Clin Transl Immunology
; 13(5): e1509, 2024.
Article
em En
| MEDLINE
| ID: mdl-38737448
ABSTRACT
Objectives:
Seasonal influenza viruses cause roughly 650 000 deaths annually despite available vaccines. CD8+ T cells typically recognise influenza-derived peptides from internal structural and non-structural influenza proteins and are an attractive avenue for future vaccine design as they could reduce the severity of disease following infection with diverse influenza strains. CD8+ T cells recognise peptides presented by the highly polymorphic Human Leukocyte Antigens class I molecules (HLA-I). Each HLA-I variant has distinct peptide binding preferences, representing a significant obstacle for designing vaccines that elicit CD8+ T cell responses across broad populations. Consequently, the rational design of a CD8+ T cell-mediated vaccine would require the identification of highly immunogenic peptides restricted to a range of different HLA molecules.Methods:
Here, we assessed the immunogenicity of six recently published novel influenza-derived peptides identified by mass-spectrometry and predicted to bind to the prevalent HLA-B*1801 molecule.Results:
Using CD8+ T cell activation assays and protein biochemistry, we showed that 3/6 of the novel peptides were immunogenic in several HLA-B*1801+ individuals and confirmed their HLA-B*1801 restriction. We subsequently compared CD8+ T cell responses towards the previously identified highly immunogenic HLA-B*1801-restricted NP219 peptide. Using X-ray crystallography, we solved the first crystal structures of HLA-B*1801 presenting immunogenic influenza-derived peptides. Finally, we dissected the first TCR repertoires specific for HLA-B*1801 restricted pathogen-derived peptides, identifying private and restricted repertoires against each of the four peptides.Conclusion:
Overall the characterisation of these novel immunogenic peptides provides additional HLA-B*1801-restricted vaccine targets derived from the Matrix protein 1 and potentially the non-structural protein and the RNA polymerase catalytic subunit of influenza viruses.
Texto completo:
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Base de dados:
MEDLINE
Idioma:
En
Revista:
Clin Transl Immunology
Ano de publicação:
2024
Tipo de documento:
Article