An immunodominant NP105–113-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease
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 Dominey-Foy, Jin Chen, 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 Kwok, Charlotte Rich‐Griffin, Wanwisa Dejnirattisa, Chang Liu, Prathiba Kurupati, Isar Nassiri, Robert Watson, Orion Tong, Chelsea Taylor, Piyush Kumar Sharma, Bo Sun, Fabiola Curion, Santiago Revale, Lucy C. Garner, Kathrin Jansen, Ricardo C. Ferreira, Moustafa Attar, Jeremy Fry, Rebecca A Russell, Hans J. Stauss, William James, Alain Townsend, Ling‐Pei Ho, Paul Klenerman, Juthathip Mongkolsapaya, Gavin Screaton, Calliope A. Dendrou, Stephen N. Sansom, Rachael Bashford-Rogers, Benny Chain, Geoffrey L. Smith, Jane A. McKeating, Benjamin P. Fairfax, Paul Bowness, Andrew J. McMichael, Graham S. Ogg, Julian C. Knight, Tao Dong
Abstract
Abstract NP 105–113 -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 NP 105–113 -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 NP 105–113 -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 NP 105–113 -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 NP 105–113 -B*07:02-specific T cell responses associate with mild disease and high antiviral efficacy, pointing to inclusion for future vaccine design.