RT Journal Article
SR Electronic
T1 Protracted yet coordinated differentiation of long-lived SARS-CoV-2-specific CD8+ T cells during COVID-19 convalescence
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.04.28.441880
DO 10.1101/2021.04.28.441880
A1 Tongcui Ma
A1 Heeju Ryu
A1 Matthew McGregor
A1 Benjamin Babcock
A1 Jason Neidleman
A1 Guorui Xie
A1 Ashley F. George
A1 Julie Frouard
A1 Victoria Murray
A1 Gurjot Gill
A1 Eliver Ghosn
A1 Evan Newell
A1 Sulggi Lee
A1 Nadia R. Roan
YR 2021
UL http://biorxiv.org/content/early/2021/04/29/2021.04.28.441880.abstract
AB 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 Nuc322-331, 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 Nuc322-331-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 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 over a ∼6-month period of convalescence. 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, into a state characteristic of long-lived, self-renewing memory.Competing Interest StatementThe authors have declared no competing interest.