SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8+ T cell activation in COVID-19 patients

Autor: Morten Nielsen, Susana Patricia Amaya Hernandez, Anne Ortved Gang, Helle Rus Povlsen, Ditte Stampe Hersby, Tripti Tamhane, Sunil Kumar Saini, Sine Reker Hadrup
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Saini, S K, Hersby, D S, Tamhane, T, Povlsen, H R, Amaya Hernandez, S P, Nielsen, M, Gang, A O & Hadrup, S R 2021, ' SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8 + T cell activation in COVID-19 patients ', Science immunology, vol. 6, no. 58, eabf7550, pp. 1-16 . https://doi.org/10.1126/sciimmunol.abf7550
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Consejo Nacional de Investigaciones Científicas y Técnicas
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Saini, S K, Hersby, D S, Tamhane, T, Povlsen, H R, Amaya Hernandez, S P, Nielsen, M, Gang, A O & Hadrup, S R 2021, ' SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8 + T cell activation in COVID-19 patients ', Science immunology, vol. 6, no. 58, eabf7550 . https://doi.org/10.1126/sciimmunol.abf7550
Popis: T cells are important for effective viral clearance, elimination of virus-infected cells and long-term disease protection. To examine the full-spectrum of CD8+ T cell immunity in COVID-19, we experimentally evaluated 3141 major histocompatibility (MHC) class I-binding peptides covering the complete SARS-CoV-2 genome. Using DNA-barcoded peptide-MHC complex (pMHC) multimers combined with a T cell phenotype panel, we report a comprehensive list of 122 immunogenic and a subset of immunodominant SARS-CoV-2 T cell epitopes. Substantial CD8+ T cell recognition was observed in COVID-19 patients, with up to 27% of all CD8+ lymphocytes interacting with SARS-CoV-2-derived epitopes. Most immunogenic regions were derived from open reading frame (ORF) 1 and ORF3, with ORF1 containing most of the immunodominant epitopes. CD8+ T cell recognition of lower affinity was also observed in healthy donors toward SARS-CoV-2-derived epitopes. This pre-existing T cell recognition signature was partially overlapping with the epitope landscape observed in COVID-19 patients and may drive the further expansion of T cell responses to SARS-CoV-2 infection. Importantly the phenotype of the SARS-CoV-2-specific CD8+ T cells, revealed a strong T cell activation in COVID-19 patients, while minimal T cell activation was seen in healthy individuals. We found that patients with severe disease displayed significantly larger SARS-CoV-2-specific T cell populations compared to patients with mild diseases and these T cells displayed a robust activation profile. These results further our understanding of T cell immunity to SARS-CoV-2 infection and hypothesize that strong antigen-specific T cell responses are associated with different disease outcomes. Fil: Saini, Sunil Kumar. Technical University of Denmark; Dinamarca Fil: Hersby, Ditte Stampe. Copenhagen University Hospital; Dinamarca Fil: Tamhane, Tripti. Technical University of Denmark; Dinamarca Fil: Povlsen, Helle Rus. Technical University of Denmark; Dinamarca Fil: Amaya Hernandez, Susana Patricia. Technical University of Denmark; Dinamarca Fil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina Fil: Gang, Anne Ortved. Copenhagen University Hospital; Dinamarca Fil: Hadrup, Sine Reker. Technical University of Denmark; Dinamarca
Databáze: OpenAIRE
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