CD8 + T cell recognition is detected throughout the SARS-CoV-2 genome and is associated with COVID-19 disease severity. 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.
【초록키워드】 COVID-19, SARS-CoV-2, Immunity, T cells, SARS-COV-2 infection, disease severity, peptide, CD8, viral clearance, Population, outcomes, lymphocyte, Epitopes, T cell, Region, SARS-CoV-2 genome, Patient, phenotype, epitope, disease, MHC, T cell response, immunodominant epitopes, COVID-19 patients, T cell activation, severe disease, COVID-19 patient, T cell epitopes, overlapping, ORF3, Activation, Frame, complex, immunogenic, T cell phenotype, ORF1, MOST, immunodominant, Complete, effective, healthy donor, robust, significantly, evaluated, ORF, subset, virus-infected cell, in healthy individuals, the SARS-CoV-2 genome, with COVID-19, with mild disease, 【제목키워드】 SARS-CoV-2, CD8, T cell, epitope mapping, immunodominance, COVID-19 patient, Activation, reveal,