Abstract
T cell responses precede antibody and may provide early control of infection. We analyzed the clonal basis of this rapid response following SARS-COV-2 infection. We applied T cell receptor (TCR) sequencing to define the trajectories of individual T cell clones immediately. In SARS-COV-2 PCR+ individuals, a wave of TCRs strongly but transiently expand, frequently peaking the same week as the first positive PCR test. These expanding TCR CDR3s were enriched for sequences functionally annotated as SARS-COV-2 specific. Epitopes recognized by the expanding TCRs were highly conserved between SARS-COV-2 strains but not with circulating human coronaviruses. Many expanding CDR3s were present at high frequency in pre-pandemic repertoires. Early response TCRs specific for lymphocytic choriomeningitis virus epitopes were also found at high frequency in the preinfection naive repertoire. High-frequency naive precursors may allow the T cell response to respond rapidly during the crucial early phases of acute viral infection.
Original language | English |
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Article number | 106937 |
Journal | iScience |
Volume | 26 |
Issue number | 6 |
Early online date | 22 May 2023 |
DOIs | |
Publication status | Published - 16 Jun 2023 |
Funding
Funding Information: Funding for COVIDsortium was donated by individuals, charitable Trusts, and corporations, including Goldman Sachs, Kenneth C. Griffin, The Guy Foundation, GW Pharmaceuticals, Kusuma Trust, and Jagclif Charitable Trust, and enabled by Barts Charity with support from UCLH Charity. R.K.G. is funded by the National Institute for Health Research (DRF-2018-11-ST2-004). J.C.M. C.M. and T.A.T. are directly and indirectly supported by the University College London Hospitals NHS Foundation Trust NHS Foundation Trust (UCLH) and Barts NIHR Biomedical Research Centers and through the British Heart Foundation (BHF) Accelerator Award (AA/18/6/34223). MM is supported by a Cancer Research UK studentship. T.A.T. is funded by a BHF Intermediate Research Fellowship (FS/19/35/34374). M.N. is supported by the Wellcome Trust (207511/Z/17/Z) and by NIHR Biomedical Research Funding to UCL and UCLH. M.K.M. is supported by UKRI/NIHR UK-CIC and Wellcome Trust (214191/Z/18/Z). G.S.T. is supported by a UK Medical Research Council Clinician Scientist Fellowship (MR/N007727/1). R.J.B. and D.M.A. are supported by UKRI/MRC Newton (MR/S019553/1, MR/R02622X/1, MR/V036939/1, MR/W020610/1), NIHR Imperial Biomedical Research Center (BRC): ITMAT, Cystic Fibrosis Trust SRC (2019SRC015), NIHR EME Fast Track (NIHR134607), NIHR Long Covid (COV-LT2-0027), Innovate UK (SBRI 10008614), and Horizon 2020 Marie Skłodowska-Curie Innovative Training Network (ITN) European Training Network (no. 860325). A.M. is supported by Rosetrees Trust, The John Black Charitable Foundation, and Medical College of St Bartholomew's Hospital Trust. B.M.C. is supported by the Rosetrees Trust, the NIHR UCLH BRC, and the Wellcome Trust. Support was also provided by UK Medical Research Council (T.D, Y.P), Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS), China (grant number: 2018-I2M-2-002) (T.D, Y.P, X.Y, G.L, S.L.F), National Institutes of Health, National Key R&D Program of China (2020YFE0202400) (T.D), NIHR Oxford Biomedical Research Centre (J.C.K, A.J.M). Conceptualization: MN, BC, Data acquisition and analysis: MM, YP, CT, MM, GN, SB, AC, JR, MW, XY, GL, SLF, TR, Visualization: CT, MM, TP, Funding acquisition: JCM, MN, Project administration: CM, TT, JCM, Supervision: TD, FB, AMcK,CM, TT, MN, BC, EG, SR-Z, CP, JG, AS, TB, DMA, RJB, MKM, Writing – original draft: MM, MN, BC, Writing – review & editing: CP, AS, RB, EG, FB, CT, BC, MM, MN, MKM, AM. Authors declare that they have no competing interests. We support inclusive, diverse and equitable conduct of research. Publisher Copyright: © 2023 The Author(s)
All Science Journal Classification (ASJC) codes
- General