Cytotoxic T lymphocytes targeting a conserved SARS-CoV-2 spike epitope are efficient serial killers.

Understanding immune response to infections and vaccines lags understanding humoral responses. While neutralizing antibody responses wane over time, T cells are instrumental in long-term immunity. We apply machine learning and time-lapse imaging microscopy in nanowell grids (TIMING) to study thousands of videos of T cells with specificity for SARS-CoV-2 eliminating targets bearing spike protein as a surrogate for viral infection. The data on effector functions, including cytokine secretion and cytotoxicity, provide the first direct evidence that cytotoxic T lymphocytes from a convalescent patient targeting an epitope conserved across all known variants of concern are serial killers capable of eliminating multiple infected target cells. These data have implications for vaccine development and for the recovery and monitoring of infected individuals.