An immunodominant NP105-113-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease.

Felce, Suet Ling 
Dong, Danning 
Mentzer, Alexander J  ORCID logo

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NP105-113-B07:02-specific CD8+ T cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP105-113-B07:02-specific T cell clones and single-cell sequencing were performed concurrently, with functional avidity and antiviral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with T cell receptor usage, transcriptome signature and disease severity (acute n = 77, convalescent n = 52). We demonstrated a beneficial association of NP105-113-B07:02-specific T cells in COVID-19 disease progression, linked with expansion of T cell precursors, high functional avidity and antiviral effector function. Broad immune memory pools were narrowed postinfection but NP105-113-B07:02-specific T cells were maintained 6 months after infection with preserved antiviral efficacy to the SARS-CoV-2 Victoria strain, as well as Alpha, Beta, Gamma and Delta variants. Our data show that NP105-113-B*07:02-specific T cell responses associate with mild disease and high antiviral efficacy, pointing to inclusion for future vaccine design.

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Aged, Amino Acid Sequence, Antibodies, Viral, Antibody Affinity, COVID-19, Cell Line, Transformed, Female, Gene Expression Profiling, HLA-B7 Antigen, Humans, Immunodominant Epitopes, Immunologic Memory, Male, Middle Aged, Nucleocapsid Proteins, Receptors, Antigen, T-Cell, SARS-CoV-2, Severity of Illness Index, T-Lymphocytes, Cytotoxic, Vaccinia virus
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Nat Immunol
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Springer Science and Business Media LLC