Viral peptide–Major Histocompatibility Complex class I (viral pMHC-I)

The viral peptide–Major Histocompatibility Complex (MHC) class I complex is a molecular assembly on the surface of infected cells that signals the presence of intracellular pathogens to the immune system (Source: Janeway's Immunobiology). It consists of a viral protein fragment, typically 8-10 amino acids long, bound to the groove of an MHC class I molecule, which is then recognized by the T-cell receptor (TCR) of CD8+ cytotoxic T lymphocytes (Source: Nature Reviews Immunology, 2019). This recognition is a cornerstone of adaptive immunity, leading to the targeted destruction of infected cells through the release of cytotoxic granules (Source: UniProt). In drug development, these complexes are targeted by TCR-engineered T cells (TCR-T) and TCR-like antibodies (TCRm) to treat chronic viral infections such as HBV, HIV, and EBV (Source: Frontiers in Immunology, 2020). For instance, SCG101 is a TCR-T therapy designed to target HBV-specific peptide-MHC complexes on hepatocytes (Source: Journal of Hepatology, 2022). However, therapeutic success is often hindered by viral strategies to downregulate MHC expression and the risk of cross-reactivity with similar human self-peptides (Source: Trends in Pharmacological Sciences, 2021).

Other names

Viral pMHCHLA-peptide complexMHC-I-restricted viral antigenPeptide-MHC class I complex

Engineered TCRs or TCR-mimetic molecules bind the viral peptide-MHC complex, facilitating the formation of an immunological synapse and subsequent cytotoxic killing of the infected cell (Source: Nature Reviews Drug Discovery, 2021).