Protracted yet coordinated differentiation of long-lived SARS-CoV-2-specific CD8+ T cells during COVID-19 convalescence

Ma, T.; Ryu, H.; McGregor, M.; Babcock, B.; Neidleman, J.; Xie, G.; George, A. F.; Frouard, J.; Murray, V.; Gill, G.; Ghosn, E.; Newell, E.; Lee, S.; Roan, N.

doi:10.1101/2021.04.28.441880

bioRxiv · 10.1101/2021.04.28.441880

Protracted yet coordinated differentiation of long-lived SARS-CoV-2-specific CD8+ T cells during COVID-19 convalescence

Ma, T.·Ryu, H.·McGregor, M.·Babcock, B.·Neidleman, J.·Xie, G.·George, A. F.·Frouard, J.·Murray, V.·Gill, G.·Ghosn, E.·Newell, E.·Lee, S.·Roan, N.

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Abstract

CD8+ T cells are important antiviral effectors that can potentiate long-lived immunity against COVID-19, but a detailed characterization of these cells has been hampered by technical challenges. We screened 21 well-characterized, longitudinally-sampled convalescent donors that recovered from mild COVID-19 against a collection of SARS-CoV-2 tetramers, and identified one participant with an immunodominant response against Nuc322-331, a peptide that is conserved in all the SARS-CoV-2 variants-of-concern reported to date. We conducted 38- parameter CyTOF phenotyping on tetramer-identified Nuc322-331-specific CD8+ T cells, and on CD4+ and CD8+ T cells recognizing the entire nucleocapsid and spike proteins from SARS- CoV-2, and took 32 serological measurements on longitudinal specimens from this participant. We discovered a coordination of the Nuc322-331-specific CD8+ T response with both the CD4+ T cell and antibody pillars of adaptive immunity. Nuc322-331-specific CD8+ T cells were predominantly central memory T cells, but continually evolved over a [~]6-month period of convalescence. We observed a slow and progressive decrease in the activation state and polyfunctionality of the Nuc322-331-specific CD8+ T cells, accompanied by an increase in their lymph-node homing and homeostatic proliferation potential. These results suggest that following a typical case of mild COVID-19, SARS-CoV-2-specific CD8+ T cells not only persist but continuously differentiate in a coordinated fashion well into convalescence, into a state characteristic of long-lived, self-renewing memory.

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Ma, T., Ryu, H., McGregor, M., Babcock, B., Neidleman, J., Xie, G., George, A. F., Frouard, J., Murray, V., Gill, G., Ghosn, E., Newell, E., Lee, S., Roan, N.. 2021-04-29. Protracted yet coordinated differentiation of long-lived SARS-CoV-2-specific CD8+ T cells during COVID-19 convalescence. https://doi.org/10.1101/2021.04.28.441880

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