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Prolonged and coordinated differentiation of long-lived SARS-CoV-2-specific CD8+ T cells during convalescence

Citation

Roan, Nadia (2021), Prolonged and coordinated differentiation of long-lived SARS-CoV-2-specific CD8+ T cells during convalescence, Dryad, Dataset, https://doi.org/10.7272/Q6D21VVD

Abstract

CD8+ T cells are important antiviral effectors that can potentiate long-lived immunity against COVID-19, but to what extent these cells coordinate with other adaptive immune processes and change during convalescence is not clear. We screened 21 well-characterized convalescent donors that recovered from mild COVID-19 against a collection of SARS-CoV-2 tetramers, to identify 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. By conducting 38-parameter CyTOF phenotyping on tetramer-identified Nuc322-331-specific CD8+ T cells in conjunction with CyTOF phenotyping of CD4+ and CD8+ T cells recognizing peptides spanning the entire Nucleocapsid and Spike proteins from SARS-CoV-2, in addition to 32 serological measurements, we discover 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 during the ~6-month period of convalescence assessed. 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.