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

Autor:	Saini SK; Department of Health Technology, Section of Experimental and Translational Immunology, Technical University of Denmark, Kongens Lyngby, Denmark. sirha@dtu.dk sukusa@dtu.dk., Hersby DS; Department of Haematology, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark., Tamhane T; Department of Health Technology, Section of Experimental and Translational Immunology, Technical University of Denmark, Kongens Lyngby, Denmark., Povlsen HR; Department of Health Technology, Section of Bioinformatics, Technical University of Denmark, Kongens Lyngby, Denmark., Amaya Hernandez SP; Department of Health Technology, Section of Experimental and Translational Immunology, Technical University of Denmark, Kongens Lyngby, Denmark., Nielsen M; Department of Health Technology, Section of Bioinformatics, Technical University of Denmark, Kongens Lyngby, Denmark., Gang AO; Department of Haematology, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark., Hadrup SR; Department of Health Technology, Section of Experimental and Translational Immunology, Technical University of Denmark, Kongens Lyngby, Denmark. sirha@dtu.dk sukusa@dtu.dk.
Jazyk:	angličtina
Zdroj:	Science immunology [Sci Immunol] 2021 Apr 14; Vol. 6 (58).
DOI:	10.1126/sciimmunol.abf7550
Abstrakt:	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. (Copyright © 2021, American Association for the Advancement of Science.)
Databáze:	MEDLINE
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