Human papillomavirus antigenic peptide–Human leukocyte antigen class I complex (HPV peptide–HLA-I complex)

Human papillomavirus (HPV) antigenic peptide–Human leukocyte antigen (HLA) class I complexes are molecular assemblies presented on the surface of HPV-infected and transformed cells. These complexes consist of a short peptide fragment derived from HPV oncoproteins, most commonly E6 or E7, bound within the groove of an HLA class I molecule, such as HLA-A*02:01 (Source: PubMed PMID: 32661153). They serve as the primary recognition signal for CD8+ cytotoxic T lymphocytes, which utilize their T-cell receptors (TCRs) to identify and eliminate cells expressing these foreign viral antigens. In the context of HPV-related cancers like cervical and oropharyngeal carcinoma, these complexes are attractive therapeutic targets because the viral proteins are constitutively expressed and absent in healthy tissues (Source: Journal for ImmunoTherapy of Cancer, 2020). Current therapeutic approaches include TCR-engineered T-cell (TCR-T) therapies and soluble TCR-based bispecific molecules designed to redirect the immune system against these specific pMHC targets (Source: ClinicalTrials.gov NCT02858310). However, the efficacy of these treatments can be hindered by tumor-mediated HLA downregulation or the high degree of HLA polymorphism in the human population, which restricts treatment to patients with specific HLA genotypes.

Other names

HPV E6/E7 peptide-HLA complexesHPV-specific pMHCHPV-HLA-I complexHPV-specific peptide-MHC complex

T-cell receptor (TCR) recognition of the specific peptide-HLA complex leading to cytotoxic T-lymphocyte activation and direct lysis of HPV-positive tumor cells.