Development of a New Off-the-Shelf Plasmacytoid Dendritic Cell–Based Approach for the Expansion and Characterization of SARS-CoV-2–Specific T Cells - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Immunology Année : 2024

Development of a New Off-the-Shelf Plasmacytoid Dendritic Cell–Based Approach for the Expansion and Characterization of SARS-CoV-2–Specific T Cells

Résumé

Global vaccination against COVID-19 has been widely successful; however, there is a need for complementary immunotherapies in severe forms of the disease and in immunocompromised patients. Cytotoxic CD8+ T cells have a crucial role in disease control, but their function can be dysregulated in severe forms of the disease. We report here a cell-based approach using a plasmacytoid dendritic cell line (PDC*line) to expand in vitro specific CD8+ responses against COVID-19 Ags. We tested the immunogenicity of eight HLA-A*02:01 restricted peptides derived from diverse SARS-Cov-2 proteins, selected by bioinformatics analyses in unexposed and convalescent donors. Higher ex vivo frequencies of specific T cells against these peptides were found in convalescent donors compared with unexposed donors, suggesting in situ T cell expansion upon viral infection. The peptide-loaded PDC*line induced robust CD8+ responses with total amplification rates that led up to a 198-fold increase in peptide-specific CD8+ T cell frequencies for a single donor. Of note, six of eight selected peptides provided significant amplifications, all of which were conserved between SARS-CoV variants and derived from the membrane, the spike protein, the nucleoprotein, and the ORF1ab. Amplified and cloned antiviral CD8+ T cells secreted IFN-γ upon peptide-specific activation. Furthermore, specific TCR sequences were identified for two highly immunogenic Ags. Hence, PDC*line represents an efficient platform to identify immunogenic viral targets for future immunotherapies.
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jeudi 18 juillet 2024
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Dates et versions

hal-04402741 , version 1 (18-01-2024)

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Anthony Maino, Axelle Amen, Joël Plumas, Lucie Bouquet, Marina Deschamps, et al.. Development of a New Off-the-Shelf Plasmacytoid Dendritic Cell–Based Approach for the Expansion and Characterization of SARS-CoV-2–Specific T Cells. Journal of Immunology, 2024, 212 (5), pp.825-833. ⟨10.4049/jimmunol.2300704⟩. ⟨hal-04402741⟩
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