Viral antigen-HLA class I peptide-MHC complex (pMHC class I)

Viral antigen-HLA class I peptide-MHC (pMHC) complexes are fundamental structures in the adaptive immune system, formed by the association of a viral-derived peptide with a Major Histocompatibility Complex (MHC) class I molecule (Nature Reviews Immunology, 2019). These complexes are presented on the surface of infected cells and are specifically recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, a process critical for the identification and elimination of intracellular pathogens (Janeway's Immunobiology, 9th ed.). In clinical development, these pMHC complexes are targeted by TCR-engineered T-cell (TCR-T) therapies and soluble TCR-based bispecifics to treat chronic viral infections and virus-associated cancers, such as those caused by Epstein-Barr Virus (EBV) or Human Papillomavirus (HPV) (Frontiers in Immunology, 2021). The therapeutic efficacy of targeting these complexes depends on the high affinity and specificity of the TCR for the unique peptide-HLA combination (Journal of Biomedical Science, 2022). However, the high diversity of HLA alleles across the human population and the ability of viruses to mutate their epitopes or downregulate HLA expression present significant challenges for broad therapeutic application (Cell, 2020).

Other names

peptide-MHC complexpHLAMHC-I-peptide complexAntigen-HLA complexViral pMHCpMHC-I

Recognition by engineered or endogenous T-cell receptors (TCRs) or TCR-mimetic antibodies, which triggers cytotoxic T-lymphocyte (CTL) activation and subsequent lysis of the infected or malignant target cell (Nature Reviews Drug Discovery, 2021).