CD8+ T cell responses in convalescent COVID-19 individuals target epitopes from the entire SARS-CoV-2 proteome and show kinetics of early differentiation.


Journal

bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187

Informations de publication

Date de publication:
08 Oct 2020
Historique:
pubmed: 15 10 2020
medline: 15 10 2020
entrez: 14 10 2020
Statut: epublish

Résumé

Characterization of the T cell response in individuals who recover from SARS-CoV-2 infection is critical to understanding its contribution to protective immunity. A multiplexed peptide-MHC tetramer approach was used to screen 408 SARS-CoV-2 candidate epitopes for CD8+ T cell recognition in a cross-sectional sample of 30 COVID-19 convalescent individuals. T cells were evaluated using a 28-marker phenotypic panel, and findings were modelled against time from diagnosis, humoral and inflammatory responses. 132 distinct SARS-CoV-2-specific CD8+ T cell epitope responses across six different HLAs were detected, corresponding to 52 unique reactivities. T cell responses were directed against several structural and non-structural virus proteins. Modelling demonstrated a coordinated and dynamic immune response characterized by a decrease in inflammation, increase in neutralizing antibody titer, and differentiation of a specific CD8+ T cell response. Overall, T cells exhibited distinct differentiation into stem-cell and transitional memory states, subsets, which may be key to developing durable protection.

Identifiants

pubmed: 33052343
doi: 10.1101/2020.10.08.330688
pmc: PMC7553170
pii:
doi:

Types de publication

Preprint

Langues

eng

Subventions

Organisme : NHLBI NIH HHS
ID : K23 HL151826
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI120938
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI128779
Pays : United States

Déclaration de conflit d'intérêts

Competing interests: H.K., H.S., F.K., D.C., B.A., A.N., E.W.N., and M.F. are shareholders and/or employees of ImmunoScape Pte Ltd. A.N. is a Board Director of ImmunoScape Pte Ltd.

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Auteurs

Hassen Kared (H)

ImmunoScape Pte Ltd, Singapore.

Andrew D Redd (AD)

Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Evan M Bloch (EM)

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Tania S Bonny (TS)

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Hermi Sumatoh (H)

ImmunoScape Pte Ltd, Singapore.

Faris Kairi (F)

ImmunoScape Pte Ltd, Singapore.

Daniel Carbajo (D)

ImmunoScape Pte Ltd, Singapore.

Brian Abel (B)

ImmunoScape Pte Ltd, Singapore.

Evan W Newell (EW)

ImmunoScape Pte Ltd, Singapore.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Maria P Bettinotti (MP)

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Sarah E Benner (SE)

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Eshan U Patel (EU)

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Kirsten Littlefield (K)

Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Oliver Laeyendecker (O)

Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Shmuel Shoham (S)

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

David Sullivan (D)

Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Arturo Casadevall (A)

Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Andrew Pekosz (A)

Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Alessandra Nardin (A)

ImmunoScape Pte Ltd, Singapore.

Michael Fehlings (M)

ImmunoScape Pte Ltd, Singapore.

Aaron Ar Tobian (AA)

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Thomas C Quinn (TC)

Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Classifications MeSH