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Characterization of pre-existing and induced SARS-CoV-2-specific CD8+ T cells

Schulien, Isabel, Kemming, Janine, Oberhardt, Valerie, Wild, Katharina, Seidel, Lea M., Killmer, Saskia, Sagar, Daul, Franziska, Salvat Lago, Marilyn, Decker, Annegrit, Luxenburger, Hendrik, Binder, Benedikt, Bettinger, Dominik, Sogukpinar, Oezlem, Rieg, Siegbert, Panning, Marcus, Huzly, Daniela, Schwemmle, Martin, Kochs, Georg, Waller, Cornelius F., Nieters, Alexandra, Duerschmied, Daniel, Emmerich, Florian, Mei, Henrik E., Schulz, Axel Ronald, Llewellyn-Lacey, Sian, Price, David A., Boettler, Tobias, Bengsch, Bertram, Thimme, Robert, Hofmann, Maike and Neumann-Haefelin, Christoph 2021. Characterization of pre-existing and induced SARS-CoV-2-specific CD8+ T cells. Nature Medicine 27 (1) 10.1038/s41591-020-01143-2

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Abstract

Emerging data indicate that SARS-CoV-2-specific CD8+ T cells targeting different viral proteins are detectable in up to 70% of convalescent individuals1,2,3,4,5. However, very little information is currently available about the abundance, phenotype, functional capacity and fate of pre-existing and induced SARS-CoV-2-specific CD8+ T cell responses during the natural course of SARS-CoV-2 infection. Here, we define a set of optimal and dominant SARS-CoV-2-specific CD8+ T cell epitopes. We also perform a high-resolution ex vivo analysis of pre-existing and induced SARS-CoV-2-specific CD8+ T cells, applying peptide-loaded major histocompatibility complex class I (pMHCI) tetramer technology. We observe rapid induction, prolonged contraction and emergence of heterogeneous and functionally competent cross-reactive and induced memory CD8+ T cell responses in cross-sectionally analyzed individuals with mild disease following SARS-CoV-2 infection and three individuals longitudinally assessed for their T cells pre- and post-SARS-CoV-2 infection. SARS-CoV-2-specific memory CD8+ T cells exhibited functional characteristics comparable to influenza-specific CD8+ T cells and were detectable in SARS-CoV-2 convalescent individuals who were seronegative for anti-SARS-CoV-2 antibodies targeting spike (S) and nucleoprotein (N). These results define cross-reactive and induced SARS-CoV-2-specific CD8+ T cell responses as potentially important determinants of immune protection in mild SARS-CoV-2 infection.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Nature Research
ISSN: 1078-8956
Date of First Compliant Deposit: 21 January 2022
Date of Acceptance: 22 October 2021
Last Modified: 27 Jan 2022 11:58
URI: https://orca.cardiff.ac.uk/id/eprint/146828

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