SARS-CoV-2 CD8⁺ T cell killing assays using replicating viruses and transgenic antigens

The quality of an antigen-specific CD8⁺ T cell repertoire is crucial for the clearance of intracellular pathogens, in particular for viral infections. Here, we describe killing assays to determine the function of CD8⁺ T cells engineered with SARS-CoV-2-specific T cell receptors in a near-physiological system for antigen presentation. We detail the use of target cells either infected with replicating SARS-CoV-2 virus or engineered with SARS-CoV-2 open reading frames. For complete details on the use and execution of this protocol, please refer to Moosmann et al. (2022) and Wagner et al. (2022).