| Autor: |
Saini, Sunil Kumar, Hersby, Ditte Stampe, Tamhane, Tripti, Povlsen, Helle Rus, Hernandez, Susana Patricia Amaya, Nielsen, Morten, Gang, Anne Ortved, Hadrup, Sine Reker |
| Zdroj: |
Science Immunology; 2021, Vol. 6 Issue 58, p1-15, 15p |
| Abstrakt: |
Mapping SARS-CoV-2 T cell recognition: Cellular immunity mediated by cytotoxic CD8+ T cells contributes to protection against viral infection, but the full spectrum of SARS-CoV-2 T cell recognition and role of preexisting T cell immunity remain incompletely understood. Saini et al. used DNA-barcoded peptide–MHC-I multimers to scan the SARS-CoV-2 genome for CD8+ T cell recognition in patients with COVID-19. Across 10 analyzed HLA molecules, 122 unique SARS-CoV-2 CD8+ T cell epitopes were detected, including 5 immunodominant epitopes primarily concentrated within ORF1. Healthy donors displayed broad T cell recognition of lower affinity and shared epitopes could be partially attributed to homology with seasonal human coronaviruses. The frequency and activation of SARS-CoV-2–specific CD8+ T cells were increased during severe compared with mild disease, highlighting differences in T cell responses associated with disease progression. 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 complex (MHC) class I–binding peptides covering the complete SARS-CoV-2 genome. Using DNA-barcoded peptide-MHC complex 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 patients with COVID-19, with up to 27% of all CD8+ lymphocytes interacting with SARS-CoV-2–derived epitopes. Most immunogenic regions were derived from open reading frame 1 (ORF1) 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 preexisting T cell recognition signature was partially overlapping with the epitope landscape observed in patients with COVID-19 and may drive the further expansion of T cell responses to SARS-CoV-2 infection. The phenotype of the SARS-CoV-2–specific CD8+ T cells revealed a strong T cell activation in patients with COVID-19, whereas 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 with 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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