Viral peptide–Major Histocompatibility Complex (pMHC) (pMHC)

Viral peptide–Major Histocompatibility Complex (pMHC) complexes are the fundamental units of immune recognition, consisting of a viral peptide fragment bound to an MHC molecule on the surface of an infected cell (4, 10). These complexes act as molecular beacons that signal the presence of intracellular pathogens to the adaptive immune system, specifically alerting T cells to the internal state of the cell (13, 18). MHC Class I typically presents endogenous viral proteins to CD8+ cytotoxic T cells, while MHC Class II presents exogenous viral antigens to CD4+ helper T cells (20, 27). In chronic infections and viral-associated cancers, such as those caused by HBV, HPV, and EBV, these complexes serve as critical therapeutic targets for advanced immunotherapies (2, 3). Strategies targeting pMHC include T-cell receptor-engineered T cells (TCR-T), virus-specific T cells (VSTs), and TCR-mimetic antibodies, which aim to bypass viral immune evasion mechanisms and restore effective clearance (1, 11, 12). However, the high polymorphism of HLA alleles and the risk of cross-reactivity with similar self-peptides present significant challenges for broad clinical application and safety (5, 13).

Other names

Viral peptide–MHC class I/II complexesAntigen-MHC complexHLA-peptide complexpHLAViral antigen-HLA complexpMHC complex

Recognition by T-cell receptors (TCRs) or TCR-mimetic antibodies/CARs, leading to cytotoxic T lymphocyte (CTL) activation, cytokine release, and lysis of the infected cell.