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

SK Saini, DS Hersby, T Tamhane, HR Povlsen… - Science …, 2021 - science.org
SK Saini, DS Hersby, T Tamhane, HR Povlsen, SPA Hernandez, M Nielsen, AO Gang…
Science immunology, 2021science.org
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 …
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.
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