Abstract
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.
Highlights
IntroductionThe COVID-19 (coronavirus disease 2019) pandemic caused by the highly infectious SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has challenged public health at an unprecedented scale, causing the death of more than 2 million people worldwide so far [1]
The COVID-19 pandemic caused by the highly infectious SARS-CoV-2 has challenged public health at an unprecedented scale, causing the death of more than 2 million people worldwide so far [1]
We show a full spectrum of T cell recognition toward SARS-CoV-2– derived peptides in healthy donors; this is detected at low frequency and shows characteristics of low-avidity interaction based on the staining index of the pMHC multimer interaction
Summary
The COVID-19 (coronavirus disease 2019) pandemic caused by the highly infectious SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has challenged public health at an unprecedented scale, causing the death of more than 2 million people worldwide so far [1]. Characteristics from the ongoing pandemic suggest that T cell recognition will be critical to mediate long-term protection against SARS-CoV-2 [2], because the antibody-mediated response seems to decline in a follow-up evaluation of convalescent patients, it is not yet understood how this affects the risk of reinfection and what antibody levels are required for disease protection [3,4,5]. Studies of the closely related SARS-CoV infection show persistent memory CD8+ T cell responses even after 11 years in SARS recovered patients without B cell responses [6, 7], emphasizing the potential role of CD8+ memory T cells in long-term protection from coronaviruses. The influence of such preexisting immunity to the T cell recognition associated with COVID-19 disease is poorly understood
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