T-cell receptor recognizing SARS-CoV-2 spike peptide–MHC complex (TCR-spike-pMHC)

T-cell receptors (TCRs) recognizing SARS-CoV-2 spike peptide–MHC complexes are specialized proteins on the surface of T lymphocytes that play a central role in the adaptive immune response to COVID-19. These receptors identify specific fragments of the viral spike protein that are processed and presented by Major Histocompatibility Complex (MHC) molecules on infected cells (Shomuradova et al., 2020). Upon recognition, the TCR initiates a signaling cascade that activates CD8+ cytotoxic T cells to destroy infected cells or CD4+ helper T cells to orchestrate the immune response (Saini et al., 2021). These receptors are the primary targets of vaccine-induced cellular immunity, which provides long-term protection against severe disease even when antibody neutralization wanes (Minervina et al., 2021). In therapeutic development, researchers are exploring TCR-engineered T-cell (TCR-T) therapies that utilize high-affinity TCRs to treat persistent or severe SARS-CoV-2 infections (Panagioti et al., 2022). However, the effectiveness of these TCRs can be challenged by viral evolution, as mutations in the spike protein may alter peptide presentation and allow the virus to escape T-cell recognition (Naranbhai et al., 2022). Understanding the structural and genetic landscape of these TCRs is essential for designing next-generation vaccines and immunotherapies that are resilient to emerging viral variants.

Other names

SARS-CoV-2 spike-specific T-cell receptorSpike-reactive T-cell receptorAnti-spike TCRSARS-CoV-2 spike-specific TCRSpike peptide-MHC-specific T-cell receptor

The T-cell receptor (TCR) specifically recognizes and binds to SARS-CoV-2 spike protein-derived peptides presented by Major Histocompatibility Complex (MHC) Class I or Class II molecules on the surface of infected cells or antigen-presenting cells. This binding event triggers intracellular signaling through the CD3 complex, leading to T-cell activation, clonal expansion, and the deployment of effector functions such as the release of perforins and granzymes to kill infected cells or the secretion of cytokines like IFN-gamma to coordinate the broader immune response (Shomuradova et al., 2020; Saini et al., 2021).