Protocol to quantify and phenotype SARS-CoV-2-specific T cell response using a rapid flow-cytometry-based whole blood assay

Monitoring antigen-specific T cell frequency, function, and phenotype is essential to assess the host immune response to pathogens or novel vaccines. Here, we describe a rapid and simple ex vivo whole blood assay to detect and phenotype the SARS-CoV-2-specific T cell response. We detail steps for whole blood stimulation with SARS-CoV-2 spike peptide and subsequent cell fixation and cryopreservation. We further describe thawing and cell staining steps for flow cytometry analysis. This approach minimizes sample manipulation and has a quick turnaround time. For complete details on the use and execution of this protocol, please refer to Riou et al. (2021).