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

Abstract

NP105-113-B*07:02-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-B*07:02-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-B*07:02-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-B*07:02-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.

• Authors: Yanchun Peng, Suet Ling Felce, Danning Dong, Frank Penkava, Alexander J Mentzer, Xuan Yao, Guihai Liu, Zixi Yin, Ji-Li Chen, Yongxu Lu, Dannielle Wellington, Peter A C Wing, Delaney C C Dominey-Foy, Chen Jin, Wenbo Wang, Megat Abd Hamid, Ricardo A Fernandes, Beibei Wang, Anastasia Fries, Xiaodong Zhuang, Neil Ashley, Timothy Rostron, Craig Waugh, Paul Sopp, Philip Hublitz, Ryan Beveridge, Tiong Kit Tan, Christina Dold, Andrew J Kwok, Charlotte Rich-Griffin, Wanwisa Dejnirattisa, Chang Liu, Prathiba Kurupati, Isar Nassiri, Robert A Watson, Orion Tong, Chelsea A Taylor, Piyush Kumar Sharma, Bo Sun, Fabiola Curion, Santiago Revale, Lucy C Garner, Kathrin Jansen, Ricardo C Ferreira, Moustafa Attar, Jeremy W Fry, Rebecca A Russell, COMBAT Consortium, Hans J Stauss, William James, Alain Townsend, Ling-Pei Ho, Paul Klenerman, Juthathip Mongkolsapaya, Gavin R Screaton, Calliope Dendrou, Stephen N Sansom, Rachael Bashford-Rogers, Benny Chain, Geoffrey L Smith, Jane A McKeating, Benjamin P Fairfax, Paul Bowness, Andrew J McMichael, Graham Ogg, Julian C Knight, Tao Dong
• Journal: Nature immunology (Nat Immunol) Vol. 23 Issue 1 Pg. 50-61 (01 2022) ISSN: 1529-2916 [Electronic] United States
• PMID: 34853448 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• Antibodies, Viral
• HLA-B*07:02 antigen
• HLA-B7 Antigen
• Immunodominant Epitopes
• Nucleocapsid Proteins
• Receptors, Antigen, T-Cell

Topics

• Aged
• Amino Acid Sequence
• Antibodies, Viral (immunology)
• Antibody Affinity (immunology)
• COVID-19 (immunology, pathology)
• Cell Line, Transformed
• Female
• Gene Expression Profiling
• HLA-B7 Antigen (immunology)
• Humans
• Immunodominant Epitopes (immunology)
• Immunologic Memory (immunology)
• Male
• Middle Aged
• Nucleocapsid Proteins (immunology)
• Receptors, Antigen, T-Cell (immunology)
• SARS-CoV-2 (immunology)
• Severity of Illness Index
• T-Lymphocytes, Cytotoxic (immunology)
• Vaccinia virus (genetics, immunology, metabolism)