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Peng, Y.* ; Felce, S.L.* ; Dong, D.* ; Penkava, F.* ; Mentzer, A.J.* ; Yao, X.* ; Liu, G.* ; Yin, Z.* ; Chen, J.L.* ; Lu, Y.* ; Wellington, D.* ; Wing, P.A.C.* ; Dominey-Foy, D.C.C.* ; Jin, C.* ; Wang, W.* ; Hamid, M.A.* ; Fernandes, R.A.* ; Wang, B.* ; Fries, A.* ; Zhuang, X.* ; Ashley, N.* ; Rostron, T.* ; Waugh, C.* ; Sopp, P.* ; Hublitz, P.* ; Beveridge, R.* ; Tan, T.K.* ; Dold, C.* ; Kwok, A.J.* ; Rich-Griffin, C.* ; Dejnirattisa, W.* ; Liu, C.* ; Kurupati, P.* ; Nassiri, I.* ; Watson, R.A.* ; Tong, O.* ; Taylor, C.A.* ; Kumar Sharma, P.* ; Sun, B.* ; Curion, F. ; Revale, S.* ; Garner, L.C.* ; Jansen, K.* ; Ferreira, R.C.* ; Attar, M.* ; Fry, J.W.* ; Russell, R.A.* ; COMBAT Consortium* ; Stauss, H.J.* ; James, W.* ; Townsend, A.J.* ; Ho, J.-P.* ; Klenerman, P.* ; Mongkolsapaya, J.* ; Screaton, G.R.* ; Dendrou, C.* ; Sansom, S.N.* ; Bashford-Rogers, R.* ; Chain, B.* ; Smith, G.L.* ; McKeating, J.A.* ; Fairfax, B.P.* ; Bowness, P.* ; McMichael, A.J.* ; Ogg, G.* ; Knight, J.C.* ; Dong, T.*

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

Nat. Immunol., DOI: 10.1038/s41590-021-01084-z (2021)
Publ. Version/Full Text DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Rna-seq; Sars-cov-2; Recombinant
ISSN (print) / ISBN 1529-2908
e-ISSN 1529-2916
Publisher Nature Publishing Group
Publishing Place Heidelberger Platz 3, Berlin, 14197, Germany
Reviewing status Peer reviewed
Grants Cancer Research UK
UK Medical Research Council (MRC)
Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS), China
National Institutes of Health, National Key R&D Program of China
China Scholarship Council
NIHR Oxford Biomedical Research Centre
Schmidt Futures
National Institute for Health Research (NIHR) (UKRIDHSC COVID-19 Rapid Response Rolling Call)
Huo Family Foundation
UK-CIC
DHSC (PITCH)
Wellcome Investigator Award
UK MRC
Oxford Biomedical Research Centre
UK RI