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Large clones of pre-existing T cells drive early immunity against SARS-COV-2 and LCMV infection.
Milighetti, Martina; Peng, Yanchun; Tan, Cedric; Mark, Michal; Nageswaran, Gayathri; Byrne, Suzanne; Ronel, Tahel; Peacock, Tom; Mayer, Andreas; Chandran, Aneesh; Rosenheim, Joshua; Whelan, Matthew; Yao, Xuan; Liu, Guihai; Felce, Suet Ling; Dong, Tao; Mentzer, Alexander J; Knight, Julian C; Balloux, Francois; Greenstein, Erez; Reich-Zeliger, Shlomit; Pade, Corinna; Gibbons, Joseph M; Semper, Amanda; Brooks, Tim; Otter, Ashley; Altmann, Daniel M; Boyton, Rosemary J; Maini, Mala K; McKnight, Aine; Manisty, Charlotte; Treibel, Thomas A; Moon, James C; Noursadeghi, Mahdad; Chain, Benny.
  • Milighetti M; Division of Infection and Immunity, University College London, London WC1E 6BT, UK.
  • Peng Y; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Tan C; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
  • Mark M; UCL Genetics Institute, University College London, London WC1E 6BT, UK.
  • Nageswaran G; Department of Systems Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Byrne S; Division of Infection and Immunity, University College London, London WC1E 6BT, UK.
  • Ronel T; Division of Infection and Immunity, University College London, London WC1E 6BT, UK.
  • Peacock T; Division of Infection and Immunity, University College London, London WC1E 6BT, UK.
  • Mayer A; Division of Infection and Immunity, University College London, London WC1E 6BT, UK.
  • Chandran A; Division of Infection and Immunity, University College London, London WC1E 6BT, UK.
  • Rosenheim J; Division of Infection and Immunity, University College London, London WC1E 6BT, UK.
  • Whelan M; Division of Infection and Immunity, University College London, London WC1E 6BT, UK.
  • Yao X; Division of Infection and Immunity, University College London, London WC1E 6BT, UK.
  • Liu G; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
  • Felce SL; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
  • Dong T; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
  • Mentzer AJ; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Knight JC; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
  • Balloux F; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Greenstein E; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
  • Reich-Zeliger S; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Pade C; UCL Genetics Institute, University College London, London WC1E 6BT, UK.
  • Gibbons JM; Department of Systems Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Semper A; Department of Systems Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Brooks T; Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 4NS, UK.
  • Otter A; Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 4NS, UK.
  • Altmann DM; UK Health Security Agency, Porton Down, Salisbury SP4 0JG, UK.
  • Boyton RJ; UK Health Security Agency, Porton Down, Salisbury SP4 0JG, UK.
  • Maini MK; UK Health Security Agency, Porton Down, Salisbury SP4 0JG, UK.
  • McKnight A; Department of Immunology and Inflammation, Imperial College London, London SW7 2BX, UK.
  • Manisty C; Department of Infectious Disease, Imperial College London, London W12 0NN, UK.
  • Treibel TA; Lung Division, Royal Brompton Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.
  • Moon JC; Division of Infection and Immunity, University College London, London WC1E 6BT, UK.
  • Noursadeghi M; Institute of Cardiovascular Sciences, University College London, London WC1E 6BT, UK.
  • Chain B; Institute of Cardiovascular Sciences, University College London, London WC1E 6BT, UK.
iScience ; 26(6): 106937, 2023 Jun 16.
Article in English | MEDLINE | ID: covidwho-2324945
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.
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Full text: Available Collection: International databases Database: MEDLINE Language: English Journal: IScience Year: 2023 Document Type: Article Affiliation country: J.isci.2023.106937

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Full text: Available Collection: International databases Database: MEDLINE Language: English Journal: IScience Year: 2023 Document Type: Article Affiliation country: J.isci.2023.106937