T-cell receptor (TCR) recognizing peptide–MHC class I complex (TCR-pMHC-I)

The T-cell receptor (TCR) recognizing the peptide–major histocompatibility complex class I (pMHC-I) is a fundamental molecular interface of the adaptive immune system (Janeway et al., 2001). This heterodimeric receptor, typically composed of alpha and beta chains, specifically identifies short intracellularly derived peptides presented on the surface of nucleated cells by MHC class I molecules (Nature Reviews Immunology, 2019). Upon binding to a specific pMHC-I complex, the TCR initiates a signaling cascade through the CD3 complex, leading to the activation of CD8+ cytotoxic T lymphocytes (CTLs) and the subsequent destruction of infected or malignant cells (StatPearls, 2023). In therapeutic contexts, this interaction is exploited through TCR-engineered T-cell (TCR-T) therapies and soluble TCR-bispecific molecules, such as ImmTACs, which redirect T-cell specificity toward tumor-associated antigens like NY-ESO-1 or gp100 (NEJM, 2021). These therapies are highly specific but require patients to possess a matching HLA allele, such as HLA-A*02:01, to ensure proper recognition (Adaptimmune, 2024). Safety concerns primarily involve systemic inflammatory responses like cytokine release syndrome and potential cross-reactivity with healthy tissues expressing similar peptides (Journal of Clinical Oncology, 2022).

Other names

TCR-pMHC-I complexCD8+ T-cell receptorMHC-I restricted T-cell receptorPeptide-HLA class I complexAntigen-specific T-cell receptor

TCR-mediated recognition of specific peptide-HLA complexes on target cells, triggering T-cell activation and cytotoxic granule release.