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Protracted yet Coordinated Differentiation of Long-Lived SARS-CoV-2-Specific CD8⁺ T Cells during Convalescence.

ABSTRACT: CD8⁺ T cells can potentiate long-lived immunity against COVID-19. We screened longitudinally-sampled convalescent human donors against SARS-CoV-2 tetramers and identified a participant with an immunodominant response against residues 322 to 311 of nucleocapsid (Nuc_322-331), a peptide conserved in all variants of concern reported to date. We conducted 38-parameter cytometry by time of flight on tetramer-identified Nuc_322-331-specific CD8⁺ T cells and on CD4⁺ and CD8⁺ T cells recognizing the entire nucleocapsid and spike proteins, and took 32 serological measurements. We discovered a coordination of the Nuc_322-331-specific CD8⁺ T response with both the CD4⁺ T cell and Ab pillars of adaptive immunity. Over the approximately six month period of convalescence monitored, we observed a slow and progressive decrease in the activation state and polyfunctionality of Nuc_322-331-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.

SUBMITTER: Ma T

PROVIDER: S-EPMC8763019 | biostudies-literature |

REPOSITORIES: biostudies-literature

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

Project description: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 Nuc 322-331 , 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 Nuc 322-331 -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 Nuc 322-331 -specific CD8+ T response with both the CD4+ T cell and antibody pillars of adaptive immunity. Nuc 322-331 -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 Nuc 322-331 -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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