SARS-CoV-2 spike protein-specific T-cell receptor (Spike-specific TCR)

The SARS-CoV-2 spike protein-specific T-cell receptor (TCR) is a heterodimeric surface protein found on CD8+ cytotoxic T cells that plays a critical role in the adaptive immune response against COVID-19 (Grifoni et al., Cell, 2020). It specifically recognizes viral peptides derived from the SARS-CoV-2 spike protein when they are presented by Major Histocompatibility Complex (MHC) class I molecules on the surface of infected or antigen-presenting cells (Dan et al., Science, 2021). Upon binding to the peptide-MHC complex, the TCR triggers a signaling cascade that leads to the activation of the T cell, resulting in the targeted destruction of infected cells through the secretion of perforins and granzymes. This mechanism is a primary target for COVID-19 vaccines, such as BNT162b2 and mRNA-1273, which aim to prime these T cells to provide long-term protection and reduce disease severity (Polack et al., NEJM, 2020). Additionally, engineered TCR-T cell therapies are being explored as potential treatments for severe or persistent infections. Understanding the diversity and longevity of these TCRs is essential for evaluating vaccine efficacy and developing next-generation immunotherapies. The specificity of these receptors ensures that the immune system can distinguish between infected and healthy cells, minimizing collateral damage. However, the emergence of viral variants with mutations in the spike protein can potentially impact the recognition efficiency of these TCRs. Research into the TCR repertoire has shown that a broad range of TCR sequences can recognize the same spike epitopes, providing a level of redundancy in the immune response. Overall, the spike-specific TCR is a cornerstone of cellular immunity and a key focus for both prophylactic and therapeutic interventions.

Other names

SARS-CoV-2 spike-reactive T-cell receptorSpike-specific CD8+ TCRSARS-CoV-2 S-specific TCR

Vaccines induce the production of spike protein, which is processed and presented on MHC class I molecules to prime and expand CD8+ T cells bearing spike-specific TCRs; these TCRs then recognize and eliminate SARS-CoV-2 infected cells (Sahin et al., Nature, 2020).