Characterization of pre-existing and induced SARS-CoV-2-specific CD8+ T cells
Open Access
- 12 November 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Medicine
- Vol. 27 (1), 78-85
- https://doi.org/10.1038/s41591-020-01143-2
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.Keywords
Funding Information
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg
This publication has 25 references indexed in Scilit:
- TCF1+ hepatitis C virus-specific CD8+ T cells are maintained after cessation of chronic antigen stimulationNature Communications, 2017
- Memory T cell responses targeting the SARS coronavirus persist up to 11 years post-infectionVaccine, 2016
- Human Influenza A Virus–Specific CD8+ T-Cell Response Is Long-livedThe Journal of Infectious Diseases, 2015
- Single-Cell Trajectory Detection Uncovers Progression and Regulatory Coordination in Human B Cell DevelopmentCell, 2014
- Fast, scalable generation of high‐quality protein multiple sequence alignments using Clustal OmegaMolecular Systems Biology, 2011
- Enumeration of human antigen–specific naive CD8+ T cells reveals conserved precursor frequenciesBlood, 2010
- Disappearance of Antibodies to SARS-Associated Coronavirus after RecoveryThe New England Journal of Medicine, 2007
- Avidity for antigen shapes clonal dominance in CD8+ T cell populations specific for persistent DNA virusesThe Journal of Experimental Medicine, 2005
- Heterologous T cell immunity in severe hepatitis C virus infectionThe Journal of Experimental Medicine, 2005
- Reliable prediction of T‐cell epitopes using neural networks with novel sequence representationsProtein Science, 2003