Human papillomavirus peptide-human leukocyte antigen complex (HPV-HLA complex)

Human papillomavirus (HPV) peptide-human leukocyte antigen (HLA) complexes are cell-surface markers formed when HPV-infected or transformed cells process viral oncoproteins, primarily E6 and E7, into short peptides and present them via HLA molecules (Stevanović et al., 2015, J Clin Oncol). These complexes serve as the primary recognition signal for the cellular immune system, specifically allowing CD8+ cytotoxic T lymphocytes to identify and eliminate HPV-positive cells (Melief et al., 2020, Sci Transl Med). In HPV-driven malignancies such as cervical and oropharyngeal cancers, these pMHC complexes are highly specific therapeutic targets because they are uniquely expressed by malignant cells and not by healthy tissue. Therapeutic strategies targeting these complexes include TCR-engineered T-cell therapies (TCR-T), therapeutic vaccines, and TCR-mimetic bispecific molecules like CUE-101 (Quayle et al., 2020, Clin Cancer Res). By engaging these complexes, drugs aim to bypass the immune suppression often found in the tumor microenvironment and induce a robust, antigen-specific anti-tumor response. However, therapeutic efficacy can be challenged by tumor-mediated HLA downregulation or the development of immune tolerance within the tumor microenvironment.

Other names

HPV E6/E7 peptide-HLA complexHPV-specific peptide-MHC complexHPV pMHCHPV-derived epitope-HLA complex

T-cell receptor (TCR) mediated recognition and subsequent cytotoxic T-lymphocyte (CTL) activation leading to apoptosis of target cells.