iScience (Jun 2023)
Large clones of pre-existing T cells drive early immunity against SARS-COV-2 and LCMV infection
- Martina Milighetti,
- Yanchun Peng,
- Cedric Tan,
- Michal Mark,
- Gayathri Nageswaran,
- Suzanne Byrne,
- Tahel Ronel,
- Tom Peacock,
- Andreas Mayer,
- Aneesh Chandran,
- Joshua Rosenheim,
- Matthew Whelan,
- Xuan Yao,
- Guihai Liu,
- Suet Ling Felce,
- Tao Dong,
- Alexander J. Mentzer,
- Julian C. Knight,
- Francois Balloux,
- Erez Greenstein,
- Shlomit Reich-Zeliger,
- Corinna Pade,
- Joseph M. Gibbons,
- Amanda Semper,
- Tim Brooks,
- Ashley Otter,
- Daniel M. Altmann,
- Rosemary J. Boyton,
- Mala K. Maini,
- Aine McKnight,
- Charlotte Manisty,
- Thomas A. Treibel,
- James C. Moon,
- Mahdad Noursadeghi,
- Benny Chain
Affiliations
- Martina Milighetti
- Division of Infection and Immunity, University College London, London WC1E 6BT, UK
- Yanchun Peng
- MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK
- Cedric Tan
- UCL Genetics Institute, University College London, London WC1E 6BT, UK
- Michal Mark
- Department of Systems Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel
- Gayathri Nageswaran
- Division of Infection and Immunity, University College London, London WC1E 6BT, UK
- Suzanne Byrne
- Division of Infection and Immunity, University College London, London WC1E 6BT, UK
- Tahel Ronel
- Division of Infection and Immunity, University College London, London WC1E 6BT, UK
- Tom Peacock
- Division of Infection and Immunity, University College London, London WC1E 6BT, UK
- Andreas Mayer
- Division of Infection and Immunity, University College London, London WC1E 6BT, UK
- Aneesh Chandran
- Division of Infection and Immunity, University College London, London WC1E 6BT, UK
- Joshua Rosenheim
- Division of Infection and Immunity, University College London, London WC1E 6BT, UK
- Matthew Whelan
- Division of Infection and Immunity, University College London, London WC1E 6BT, UK
- Xuan Yao
- Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK
- Guihai Liu
- Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK
- Suet Ling Felce
- Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK
- Tao Dong
- MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK
- Alexander J. Mentzer
- Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK
- Julian C. Knight
- Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK
- Francois Balloux
- UCL Genetics Institute, University College London, London WC1E 6BT, UK
- Erez Greenstein
- Department of Systems Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel
- Shlomit Reich-Zeliger
- Department of Systems Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel
- Corinna Pade
- Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 4NS, UK
- Joseph M. Gibbons
- Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 4NS, UK
- Amanda Semper
- UK Health Security Agency, Porton Down, Salisbury SP4 0JG, UK
- Tim Brooks
- UK Health Security Agency, Porton Down, Salisbury SP4 0JG, UK
- Ashley Otter
- UK Health Security Agency, Porton Down, Salisbury SP4 0JG, UK
- Daniel M. Altmann
- Department of Immunology and Inflammation, Imperial College London, London SW7 2BX, UK
- Rosemary J. Boyton
- Department of Infectious Disease, Imperial College London, London W12 0NN, UK; Lung Division, Royal Brompton Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, UK
- Mala K. Maini
- Division of Infection and Immunity, University College London, London WC1E 6BT, UK
- Aine McKnight
- Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 4NS, UK
- Charlotte Manisty
- Institute of Cardiovascular Sciences, University College London, London WC1E 6BT, UK
- Thomas A. Treibel
- Institute of Cardiovascular Sciences, University College London, London WC1E 6BT, UK
- James C. Moon
- Institute of Cardiovascular Sciences, University College London, London WC1E 6BT, UK
- Mahdad Noursadeghi
- Division of Infection and Immunity, University College London, London WC1E 6BT, UK
- Benny Chain
- Division of Infection and Immunity, University College London, London WC1E 6BT, UK; Corresponding author
- Journal volume & issue
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Vol. 26,
no. 6
p. 106937
Abstract
Summary: 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.
