Yanchun PengAlexander J. MentzerGuihai LiuXuan YaoZixi YinDanning DongWanwisa DejnirattisaiTimothy RostronPiyada SupasaChang LiuCésar López-CamachoJose Slon-CamposYuguang ZhaoDavid I. StuartGuido C. PaesenJonathan M. GrimesAlfred A. AntsonOliver W. BayfieldDorothy E.D.P. HawkinsDe Sheng KerBeibei WangLance TurtleKrishanthi SubramaniamPaul ThomsonPing ZhangChristina DoldJeremy RatcliffPeter SimmondsThushan de SilvaPaul SoppDannielle WellingtonUshani RajapaksaYi Ling ChenMariolina SalioGiorgio NapolitaniWayne PaesPersephone BorrowBenedikt M. KesslerJeremy W. FryNikolai F. SchwabeMalcolm G. SempleJ. Kenneth BaillieShona C. MoorePeter J.M. OpenshawM. Azim AnsariSusanna DunachieEleanor BarnesJohn FraterGeorgina KerrPhilip GoulderTeresa LockettRobert LevinYonghong ZhangRonghua JingLing Pei HoEleanor BarnesDanning DongTao DongSusanna DunachieJohn FraterPhilip GoulderGeorgina KerrPaul KlenermanGuihai LiuAndrew McMichaelGraham OggYanchun PengMariolina SalioXuan YaoZixi YinJ. Kenneth BailliePaul KlenermanAlexander J. MentzerShona C. MoorePeter J.M. OpenshawMalcolm G. SempleDavid I. StuartRichard J. CornallChristopher P. ConlonPaul KlenermanGavin R. ScreatonJuthathip MongkolsapayaAndrew McMichaelJulian C. KnightGraham OggTao DongNIHR Oxford Biomedical Research CentreOxford University Hospitals NHS Foundation TrustLiverpool University Hospitals NHS Foundation TrustBeijing YouAn Hospital, Capital Medical UniversityDiamond Light SourceThe Wellcome Centre for Human GeneticsWorthing HospitalThe University of EdinburghUniversity of OxfordAlder Hey Children's HospitalXinjiang Medical UniversityUniversity of LiverpoolUniversity of YorkFaculty of Medicine, Siriraj Hospital, Mahidol UniversityNational Heart and Lung InstituteNuffield Department of MedicineThe Sheffield Medical SchoolUniversity of Oxford Medical Sciences DivisionProImmune2020-10-052020-10-052020-01-01Nature Immunology. (2020)15292916152929082-s2.0-85090233862https://repository.li.mahidol.ac.th/handle/20.500.14594/59134© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. 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.Mahidol UniversityImmunology and MicrobiologyMedicineArticleSCOPUS10.1038/s41590-020-0782-6