Ex vivo detection of SARS-CoV-2-specific CD8+ T cells: rapid induction, prolonged contraction, and formation of functional memory

Schulien, I.; Kemming, J.; Oberhardt, V.; Wild, K.; Seidel, L. M.; Killmer, S.; Sagar,; Daul, F.; Salvat Lago, M.; Decker, A.; Luxenburger, H.; Binder, B.; Bettinger, D.; Sogukpinar, O.; Rieg, S.; Panning, M.; Huzly, D.; Schwemmle, M.; Kochs, G.; Waller, C. F.; Nieters, A.; Duerschmied, D.; Emmerich, F.; Mei, H.; Schulz, A.; Llewellyn-Lacey, S.; Price, D. A.; Boettler, T.; Bengsch, B.; Thimme, R.; Hofmann, M.; Neumann-Haefelin, C.

doi:10.1101/2020.08.13.249433

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bioRxiv · 10.1101/2020.08.13.249433

Ex vivo detection of SARS-CoV-2-specific CD8+ T cells: rapid induction, prolonged contraction, and formation of functional memory

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Abstract

CD8+ T cells are critical for the elimination and long-lasting protection of many viral infections, but their role in the current SARS-CoV-2 pandemic is unclear. Emerging data indicates that SARS-CoV-2-specific CD8+ T cells are detectable in the majority of individuals recovering from SARS-CoV-2 infection. However, optimal virus-specific epitopes, the role of pre-existing heterologous immunity as well as their kinetics and differentiation program during disease control have not been defined in detail. Here, we show that both pre-existing and newly induced SARS-CoV-2-specific CD8+ T-cell responses are potentially important determinants of immune protection in mild SARS-CoV-2 infection. In particular, our results can be summarized as follows: First, immunodominant SARS-CoV-2-specific CD8+ T-cell epitopes are targeted in the majority of individuals with convalescent SARS-CoV-2 infection. Second, MHC class I tetramer analyses revealed the emergence of phenotypically diverse and functionally competent pre-existing and newly induced SARS-CoV-2-specific memory CD8+ T cells that showed similar characteristics compared to influenza-specific CD8+ T cells. Third, SARS-CoV-2-specific CD8+ T-cell responses are more robustly detectable than antibodies against the SARS-CoV-2-spike protein. This was confirmed in a longitudinal analysis of acute-resolving infection that demonstrated rapid induction of the SARS-CoV-2-specific CD8+ T cells within a week followed by a prolonged contraction phase that outlasted the waning humoral immune response indicating that CD8+ T-cell responses might serve as a more precise correlate of antiviral immunity than antibody measurements after convalescence. Collectively, these data provide new insights into the fine specificity, heterogeneity, and dynamics of SARS-CoV-2-specific memory CD8+ T cells, potentially informing the rational development of a protective vaccine against SARS-CoV-2.

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Schulien, I., Kemming, J., Oberhardt, V., Wild, K., Seidel, L. M., Killmer, S., Sagar,, Daul, F., Salvat Lago, M., Decker, A., Luxenburger, H., Binder, B., Bettinger, D., Sogukpinar, O., Rieg, S., Panning, M., Huzly, D., Schwemmle, M., Kochs, G., Waller, C. F., Nieters, A., Duerschmied, D., Emmerich, F., Mei, H., Schulz, A., Llewellyn-Lacey, S., Price, D. A., Boettler, T., Bengsch, B., Thimme, R., Hofmann, M., Neumann-Haefelin, C.. 2020-08-14. Ex vivo detection of SARS-CoV-2-specific CD8+ T cells: rapid induction, prolonged contraction, and formation of functional memory. https://doi.org/10.1101/2020.08.13.249433

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