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 (TCRs) 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; Wagner et al., 2022).