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

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.