T-cell receptor-Major Histocompatibility Complex (TCR-MHC)

The T-cell receptor-Major Histocompatibility Complex (TCR-MHC) is the fundamental molecular interaction driving adaptive immunity (Nature Reviews Immunology, 2010). It consists of a T-cell receptor binding to a peptide fragment presented by a Major Histocompatibility Complex molecule, known as Human Leukocyte Antigen (HLA) in humans (StatPearls, 2023). This interaction allows T cells to monitor the internal proteome of cells, identifying pathogens or mutations that are processed into peptides (Frontiers in Immunology, 2021). In oncology, this complex is targeted by TCR-engineered T-cell (TCR-T) therapies and bispecific T-cell engagers to induce potent anti-tumor responses (Journal of Hematology & Oncology, 2021). Drugs like Afamitresgene autoleucel and Tebentafusp specifically target these complexes to treat synovial sarcoma and uveal melanoma, respectively (FDA, 2022; FDA, 2024). Unlike CAR-T therapies that target surface proteins, TCR-MHC targeting enables the recognition of intracellular antigens, greatly expanding the pool of therapeutic targets (Nature Reviews Drug Discovery, 2023). However, the requirement for specific HLA alleles limits these therapies to subsets of the population (Molecular Cancer, 2022). Safety concerns include cytokine release syndrome and potential off-target cross-reactivity with healthy tissues (Journal for ImmunoTherapy of Cancer, 2020).

Other names

TCR-pMHC complexT-cell receptor-peptide-MHC complexTCR-HLA complexAntigen-MHC complex

Engineered T-cell therapy (TCR-T) and bispecific T-cell engagers (ImmTACs) that redirect T-cell cytotoxicity toward specific peptide-MHC complexes on target cells.