We conducted 38-parameter cytometry by time of flight on tetramer-identified Nuc322–331–specific CD8+ T cells and on CD4+ and CD8+ T cells recognizing the entire nucleocapsid and spike proteins, and took 32 serological measurements. 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. Five longitudinal specimens were collected from acute COVID-19infected individuals, the first within 31 d of symptom onset or SARS-CoV-2 exposure (week 0, baseline visit), followed by collections at 1, 3, 10, and 24 wk from baseline visit.
