Viral peptide–Human Leukocyte Antigen class I complex (pHLA-I)

Viral peptide–Human Leukocyte Antigen (HLA) class I complexes are molecular assemblies consisting of a viral-derived peptide fragment bound to an HLA class I molecule on the surface of infected cells (Rock et al., 2016, Trends in Immunology). These complexes are essential for the adaptive immune system, as they allow CD8+ cytotoxic T lymphocytes to recognize and eliminate cells harboring intracellular pathogens. The HLA class I molecule, composed of a polymorphic heavy chain and beta-2 microglobulin, presents peptides typically 8–11 amino acids in length that are generated through the proteasomal degradation of viral proteins. In therapeutic development, these complexes are targeted by engineered T-cell receptor (TCR) therapies and TCR-like antibodies to treat chronic viral infections, such as Hepatitis B, and virus-associated malignancies, such as HPV-related cervical cancer or EBV-related lymphomas (Yuan et al., 2021, Nature Reviews Drug Discovery). A significant challenge in targeting these complexes is the high degree of HLA polymorphism in the human population, necessitating HLA-specific drug design, and the potential for lethal off-target cross-reactivity with similar self-peptides.

Other names

Viral peptide-MHC class I complexpMHC-IHLA-I-peptide complexViral antigen-HLA complexPeptide-MHC complex

Recognition by engineered T-cell receptors (TCRs) or TCR-like antibodies to induce targeted cell lysis of infected or malignant cells (Yuan et al., 2021, Nature Reviews Drug Discovery).