1. Identification and characterization of a SARS-CoV-2 specific CD8 + T cell response with immunodominant features.
- Author
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Gangaev A, Ketelaars SLC, Isaeva OI, Patiwael S, Dopler A, Hoefakker K, De Biasi S, Gibellini L, Mussini C, Guaraldi G, Girardis M, Ormeno CMPT, Hekking PJM, Lardy NM, Toebes M, Balderas R, Schumacher TN, Ovaa H, Cossarizza A, and Kvistborg P
- Subjects
- Adult, Aged, Aged, 80 and over, Alleles, CD8-Positive T-Lymphocytes pathology, COVID-19 pathology, Epitopes, T-Lymphocyte immunology, Female, Histocompatibility Antigens Class I genetics, Histocompatibility Antigens Class I immunology, Humans, Immunodominant Epitopes chemistry, Immunologic Memory, Lymphocyte Activation, Male, Middle Aged, Polyproteins immunology, Viral Proteins immunology, CD8-Positive T-Lymphocytes immunology, COVID-19 immunology, Immunodominant Epitopes immunology, SARS-CoV-2 immunology
- 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.- Published
- 2021
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