4.8 Article

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

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NATURE MEDICINE
卷 27, 期 1, 页码 78-+

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NATURE PORTFOLIO
DOI: 10.1038/s41591-020-01143-2

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资金

  1. Medical Faculty - Federal Ministry of Education and Research [01KI1722]
  2. COVID-19 research grant of the Ministry of Science, Research and Art, State of Baden-Wuerttemberg [CRC 1160-Project A02, CRC/TRR 179-Project 02, CRC 1160-Project A06, CRC/TRR 179-Project 04, BE-5496/5-1]
  3. German Research Foundation (DFG) [272983813, CRC 1160, 256073931]
  4. Margarete von Wrangell fellowship (State of Baden-Wuerttemberg)
  5. Berta-Ottenstein Programme, Faculty of Medicine, University of Freiburg
  6. DFG [ME3644/5-1, 324736178]
  7. Wellcome Trust Senior Investigator Award [100326/Z/12/Z]

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The study found that SARS-CoV-2 infection induces and forms functionally competent memory CD8(+) T cell responses, which can persist in some SARS-CoV-2 convalescent individuals. Even in the absence of virus-specific antibodies, these virus epitope-specific CD8(+) T cell responses are induced following infection.
Emerging data indicate that SARS-CoV-2-specific CD8(+) T cells targeting different viral proteins are detectable in up to 70% of convalescent individuals(1-5). 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. Functionally competent memory CD8(+) T cells specific for different viral epitopes are induced by SARS-CoV-2 infection and can be detected in the absence of virus-specific antibodies.

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