T cell receptor recognizing SARS-CoV-2 spike-derived peptide–MHC complexes (SARS-CoV-2 Spike-specific TCR)

The T cell receptor (TCR) recognizing SARS-CoV-2 spike-derived peptide–MHC complexes is a critical component of the adaptive immune response against COVID-19. These TCRs, typically composed of alpha and beta chains, specifically bind to viral epitopes—such as the immunodominant YLQPRTFLL peptide—when presented by Major Histocompatibility Complex (MHC) molecules, most commonly HLA-A*02:01. This interaction is the primary mechanism by which CD8+ cytotoxic T cells identify and destroy cells infected with the SARS-CoV-2 virus. In a therapeutic context, these TCRs are being utilized in the development of TCR-engineered T cell (TCR-T) therapies, where a patient's T cells are modified to express high-affinity receptors targeting the spike protein. While highly effective at clearing viral loads, challenges include the requirement for specific HLA matching and the potential for 'off-target' reactivity if the TCR cross-reacts with similar human protein sequences. Monitoring these TCR-pMHC interactions is also vital for assessing vaccine efficacy and long-term immunity.

Other names

Spike-reactive T cell receptorSARS-CoV-2 spike-specific TCRTCR-pMHC complex (Spike)Anti-SARS-CoV-2 TCR

Engineered or endogenous T cell receptors bind specifically to SARS-CoV-2 spike protein fragments (peptides) presented on the surface of infected cells by Major Histocompatibility Complex (MHC) molecules. This binding triggers T cell activation, leading to the release of cytotoxic granules (perforin/granzyme) and pro-inflammatory cytokines to eliminate the virus-infected cells.