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

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...

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Bibliographic Details
Published in:Nature communications Vol. 12; no. 1; pp. 2593 - 14
Main Authors: Gangaev, Anastasia, Ketelaars, Steven L. C., Isaeva, Olga I., Patiwael, Sanne, Dopler, Anna, Hoefakker, Kelly, De Biasi, Sara, Gibellini, Lara, Mussini, Cristina, Guaraldi, Giovanni, Girardis, Massimo, Ormeno, Cami M. P. Talavera, Hekking, Paul J. M., Lardy, Neubury M., Toebes, Mireille, Balderas, Robert, Schumacher, Ton N., Ovaa, Huib, Cossarizza, Andrea, Kvistborg, Pia
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 10.05.2021
Nature Publishing Group
Nature Portfolio
Subjects:
38/1
38/91
49/31
631/250/1619/554/1834
631/250/2152
631/250/255
Adult
Aged
Aged, 80 and over
Alleles
Antigens
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - pathology
Cell activation
Cell migration
Cell recognition
Convalescence
Coronaviruses
COVID-19
COVID-19 - immunology
COVID-19 - pathology
Cytokines
Epitopes
Epitopes, T-Lymphocyte - immunology
Female
Gene expression
Histocompatibility antigen HLA
Histocompatibility Antigens Class I - genetics
Histocompatibility Antigens Class I - immunology
Humanities and Social Sciences
Humans
Immune response
Immunodominance
Immunodominant Epitopes - chemistry
Immunodominant Epitopes - immunology
Immunogenicity
Immunologic Memory
Immunological memory
Lymphocyte Activation
Lymphocytes
Lymphocytes T
Male
Memory cells
Middle Aged
multidisciplinary
Pandemics
Polyproteins - immunology
SARS-CoV-2 - immunology
Science
Science (multidisciplinary)
Severe acute respiratory syndrome coronavirus 2
Viral diseases
Viral Proteins - immunology
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary: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. Many viral antigens have been identified in patients with COVID-19 patients, but which of these result in meaningful immune responses is unclear. Here the authors identify a range of SARS-CoV-2 CD8 + T cell responses across patients including a response targeting an epitope of ORF1ab with immunodominant properties.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-021-22811-y