SARS-CoV-2 spike protein-specific T-cell receptor (MHC class II restricted) (Spike-specific TCR (MHC II))

T-cell receptors (TCRs) recognizing spike-derived peptides on MHC class II are specialized protein complexes found on the surface of CD4+ T-helper cells that play a pivotal role in the adaptive immune response to SARS-CoV-2 (Grifoni et al., 2020, Cell). These receptors specifically identify and bind to fragments of the viral spike protein that have been processed and presented by Major Histocompatibility Complex (MHC) class II molecules on professional antigen-presenting cells like dendritic cells and B-cells. This recognition event is the primary trigger for CD4+ T-cell activation, which subsequently coordinates the production of high-affinity antibodies by B-cells and supports the development of cytotoxic CD8+ T-cell responses (Sette & Crotty, 2021, Cell). In clinical practice, these TCRs are central to the efficacy of COVID-19 vaccines, which aim to prime the immune system to recognize these specific viral epitopes. Furthermore, they are being investigated as therapeutic targets in TCR-engineered T-cell (TCR-T) therapies for immunocompromised individuals and serve as critical biomarkers for assessing the breadth and longevity of protective immunity (Low et al., 2021, Nature Communications). Challenges in targeting these receptors include the high degree of HLA polymorphism in the human population and the potential for viral mutations to escape TCR recognition.

Other names

SARS-CoV-2 spike-reactive TCRCD4+ T-cell receptor for spike proteinSpike-specific TCRMHC II-restricted spike TCRSARS-CoV-2 S-specific TCR

Recognition of specific SARS-CoV-2 spike protein peptides presented by Major Histocompatibility Complex (MHC) class II molecules on antigen-presenting cells, triggering CD4+ T-cell activation and subsequent immune coordination (Mateus et al., 2020, Science).