Identification and characterization of a SARS-CoV-2 specific CD8+ T cell response with immunodominant features

Anastasia Gangaev, Steven L. C. Ketelaars, Olga I. Isaeva, Sanne Patiwael, Anna Dopler, Kelly Hoefakker, Sara Biasi, Lara Gibellini, Cristina Mussini, Giovanni Guaraldi, Massimo Girardis, Cami M. P. Talavera Ormeno, Paul J. M. Hekking, Neubury M. Lardy, Mireille Toebes, Robert Balderas, Ton N. Schumacher, Huib Ovaa, Andrea Cossarizza and Pia Kvistborg ()
Additional contact information
Anastasia Gangaev: The Netherlands Cancer Institute
Steven L. C. Ketelaars: The Netherlands Cancer Institute
Olga I. Isaeva: The Netherlands Cancer Institute
Sanne Patiwael: The Netherlands Cancer Institute
Anna Dopler: The Netherlands Cancer Institute
Kelly Hoefakker: The Netherlands Cancer Institute
Sara Biasi: University of Modena and Reggio Emilia School of Medicine
Lara Gibellini: University of Modena and Reggio Emilia School of Medicine
Cristina Mussini: University of Modena and Reggio Emilia School of Medicine
Giovanni Guaraldi: University of Modena and Reggio Emilia School of Medicine
Massimo Girardis: University of Modena and Reggio Emilia School of Medicine
Cami M. P. Talavera Ormeno: Leiden University Medical Center
Paul J. M. Hekking: Leiden University Medical Center
Neubury M. Lardy: Sanquin Diagnostics B.V.
Mireille Toebes: The Netherlands Cancer Institute
Robert Balderas: BD Biosciences
Ton N. Schumacher: The Netherlands Cancer Institute
Huib Ovaa: Leiden University Medical Center
Andrea Cossarizza: University of Modena and Reggio Emilia School of Medicine
Pia Kvistborg: The Netherlands Cancer Institute

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract The COVID-19 pandemic caused by SARS-CoV-2 is a continuous challenge worldwide, and there is an urgent need to map the landscape of immunogenic and immunodominant epitopes recognized by CD8+ T cells. Here, we analyze samples from 31 patients with COVID-19 for CD8+ T cell recognition of 500 peptide-HLA class I complexes, restricted by 10 common HLA alleles. We identify 18 CD8+ T cell recognized SARS-CoV-2 epitopes, including an epitope with immunodominant features derived from ORF1ab and restricted by HLA-A*01:01. In-depth characterization of SARS-CoV-2-specific CD8+ T cell responses of patients with acute critical and severe disease reveals high expression of NKG2A, lack of cytokine production and a gene expression profile inhibiting T cell re-activation and migration while sustaining survival. SARS-CoV-2-specific CD8+ T cell responses are detectable up to 5 months after recovery from critical and severe disease, and these responses convert from dysfunctional effector to functional memory CD8+ T cells during convalescence.

Date: 2021
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DOI: 10.1038/s41467-021-22811-y

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