2. Academic Validation
  3. Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19

Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19

  • Nat Immunol. 2020 Nov;21(11):1336-1345. doi: 10.1038/s41590-020-0782-6.
Yanchun Peng # 1 2,  Alexander J Mentzer # 3 4 5,  Guihai Liu # 2 4 6,  Xuan Yao # 1 2 4,  Zixi Yin # 1 2,  Danning Dong # 2 4 7,  Wanwisa Dejnirattisai # 4,  Timothy Rostron 8,  Piyada Supasa 4,  Chang Liu 2 4,  César López-Camacho 3 4,  Jose Slon-Campos 4,  Yuguang Zhao 4,  David I Stuart 2 3 4 9,  Guido C Paesen 3,  Jonathan M Grimes 3 4 9,  Alfred A Antson 10,  Oliver W Bayfield 10,  Dorothy E D P Hawkins 10,  De-Sheng Ker 10,  Beibei Wang 2 4,  Lance Turtle 11 12,  Krishanthi Subramaniam 12,  Paul Thomson 12,  Ping Zhang 4,  Christina Dold 13 14,  Jeremy Ratcliff 4,  Peter Simmonds 4,  Thushan de Silva 15,  Paul Sopp 8,  Dannielle Wellington 1 2,  Ushani Rajapaksa 2 4,  Yi-Ling Chen 1,  Mariolina Salio 1,  Giorgio Napolitani 1,  Wayne Paes 4,  Persephone Borrow 4,  Benedikt M Kessler 2 4,  Jeremy W Fry 16,  Nikolai F Schwabe 16,  Malcolm G Semple 12 17,  J Kenneth Baillie 18,  Shona C Moore 12,  Peter J M Openshaw 19,  M Azim Ansari 4,  Susanna Dunachie 4 5,  Eleanor Barnes 4 5 20,  John Frater 4 5,  Georgina Kerr 4,  Philip Goulder 4 5,  Teresa Lockett 5,  Robert Levin 21,  Yonghong Zhang 2 6,  Ronghua Jing 6,  Ling-Pei Ho 1 2 4 20,  Oxford Immunology Network Covid-19 Response T cell Consortium,  ISARIC4C Investigators,  Richard J Cornall 1 4 5,  Christopher P Conlon 2 4 5,  Paul Klenerman 4 5 20,  Gavin R Screaton 4 5 20,  Juthathip Mongkolsapaya 2 4 20 22,  Andrew McMichael 2 4,  Julian C Knight 2 3 4 5,  Graham Ogg 1 2 5 20,  Tao Dong 23 24 25
Affiliations

Affiliations

  • 1 MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • 2 Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
  • 3 Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
  • 4 Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • 5 Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • 6 Beijing You'an Hospital, Capital Medical University, Beijing, China.
  • 7 CAMS Key Laboratory of Tumor Immunology and Radiation Therapy, Xinjiang Tumor Hospital, Xinjiang Medical University, Xinjiang, China.
  • 8 Sequencing and Flow Cytometry Facility, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • 9 Diamond Light Source, Didcot, UK.
  • 10 York Structural Biology Laboratory, Department of Chemistry, University of York, York, UK.
  • 11 Tropical and Infectious Diseases Unit, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.
  • 12 NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
  • 13 Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • 14 NIHR Oxford Biomedical Research Centre, Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford, UK.
  • 15 The Florey Institute for Host-Pathogen Interactions, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.
  • 16 ProImmune, Oxford, UK.
  • 17 Respiratory Medicine, Institute in The Park, Alder Hey Children's Hospital, Liverpool, UK.
  • 18 Anaesthesia, Critical Care and Pain Medicine Division of Health Sciences, University of Edinburgh, Edinburgh, UK.
  • 19 National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, UK.
  • 20 NIHR Oxford Biomedical Research Centre, Oxford, UK.
  • 21 Worthing Hospital, Worthing, UK.
  • 22 Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
  • 23 MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. tao.dong@imm.ox.ac.uk.
  • 24 Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. tao.dong@imm.ox.ac.uk.
  • 25 Nuffield Department of Medicine, University of Oxford, Oxford, UK. tao.dong@imm.ox.ac.uk.
  • # Contributed equally.
PMID: 32887977 DOI: 10.1038/s41590-020-0782-6
Abstract

The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and therapeutics will depend on understanding viral immunity. We studied T cell memory in 42 patients following recovery from COVID-19 (28 with mild disease and 14 with severe disease) and 16 unexposed donors, using interferon-γ-based assays with Peptides spanning SARS-CoV-2 except ORF1. The breadth and magnitude of T cell responses were significantly higher in severe as compared with mild cases. Total and spike-specific T cell responses correlated with spike-specific antibody responses. We identified 41 Peptides containing CD4+ and/or CD8+ epitopes, including six immunodominant regions. Six optimized CD8+ epitopes were defined, with peptide-MHC pentamer-positive cells displaying the central and effector memory phenotype. In mild cases, higher proportions of SARS-CoV-2-specific CD8+ T cells were observed. The identification of T cell responses associated with milder disease will support an understanding of protective immunity and highlights the potential of including non-spike proteins within future COVID-19 vaccine design.

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