Using spectral flow cytometry combined with cellular indexing of transcriptomes and T cell receptor (TCR) sequencing we longitudinally characterize individual SARS-CoV-2-specific CD8+ T cells of COVID-19 patients from acute infection to one year into recovery and find a distinct signature identifying long-lived memory CD8+ T cells.
SARS-CoV-2-specific memory CD8+ T cells persisting one year after acute infection express CD45RA, interleukin-7 receptor α (CD127), and T cell factor-1 (TCF1), but they maintain low CCR7, thus resembling CD45RA+ effector-memory T (TEMRA) cells.
Tracking individual clones of SARS-CoV-2-specific CD8+ T cells, we reveal that an interferon signature marks clones giving rise to long-lived cells, whereas prolonged proliferation and mammalian target of rapamycin (mTOR) signaling are associated with clonal disappearance from the blood.
Collectively, we describe a transcriptional signature that marks long-lived, circulating human memory CD8+ T cells following an acute virus infection.
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