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

Viral peptide–Major Histocompatibility Complex (MHC) class I complexes are heterotrimeric structures consisting of a polymorphic heavy chain, a light chain (beta-2 microglobulin), and a short viral peptide (typically 8–10 amino acids). These complexes are expressed on the surface of almost all nucleated cells and serve as the primary mechanism for the immune system to monitor intracellular viral infections. When a cell is infected, viral proteins are proteolytically degraded into peptides, which are then loaded onto MHC-I molecules in the endoplasmic reticulum and transported to the cell surface (Source: NIH/NCBI, 2023). In the context of drug development, these complexes are highly specific targets for immunotherapies such as TCR-engineered T cells and TCR-mimetic antibodies. Unlike traditional antibodies that target surface proteins, pMHC-I targeting allows the immune system to recognize and eliminate cells based on internal viral signatures. This approach is particularly relevant for chronic viral infections like HBV, HIV, and HPV-related cancers, where the target is the specific presentation of a viral epitope that distinguishes infected or transformed cells from healthy tissue (Source: Frontiers in Immunology, 2022; PubMed: 35464412).

Other names

Viral pMHC-IPeptide-HLA class I complexViral antigen-MHC I complexpMHC class IMHC-I-peptide complex

Therapeutic agents such as TCR-engineered T cells (TCR-T) or bispecific T-cell engagers (ImmTACs) bind specifically to the viral peptide presented within the MHC class I groove. This binding mimics the natural immunological synapse, leading to the activation of cytotoxic T lymphocytes and the subsequent lysis of the infected cell through the release of perforins and granzymes (Source: Nature Reviews Drug Discovery, 2021; PubMed: 33510449).