Protracted yet Coordinated Differentiation of Long-Lived SARS-CoV-2-Specific CD8+ T Cells during Convalescence
Tongcui Ma, Heeju Ryu, Matthew McGregor, Benjamin Babcock, Jason Neidleman, Guorui Xie, Ashley F. George, Julie Frouard, Victoria Murray, Gurjot Gill, Eliver Ghosn, Evan W. Newell, Sulggi A. Lee, Nadia R. Roan
Abstract
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 (Nuc322–331), a peptide conserved in all variants of concern reported to date. 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. We discovered a coordination of the Nuc322–331–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 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.