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

A Gangaev, SLC Ketelaars, OI Isaeva… - Nature …, 2021 - nature.com
A Gangaev, SLC Ketelaars, OI Isaeva, S Patiwael, A Dopler, K Hoefakker, S De Biasi
Nature Communications, 2021nature.com
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 …
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.
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