Human papillomavirus type 16 E7 oncoprotein peptide–MHC complex (HPV16 E7 pMHC)

The Human papillomavirus type 16 (HPV16) E7 oncoprotein is a critical driver of oncogenesis in HPV-associated cancers, such as cervical and oropharyngeal carcinomas (UniProt P03129). It functions primarily by binding to and inducing the degradation of the retinoblastoma protein (pRb), which releases E2F transcription factors and promotes aberrant S-phase entry (PubMed: 10482235). For therapeutic purposes, specific epitopes of the E7 protein, such as the E7 11-19 peptide, are processed and presented on the surface of tumor cells as peptide-MHC (pMHC) complexes, most commonly in association with HLA-A*02:01 (PubMed: 28350742). These pMHC complexes serve as highly specific targets for T-cell receptor (TCR)-engineered T cells and TCR-like antibodies, allowing the immune system to selectively identify and eliminate malignant cells while sparing healthy tissue (PubMed: 30530749). Targeting the HPV16 E7 pMHC complex is a major focus in the development of adoptive cell therapies, such as KITE-439 and P-HPV16-01, aimed at treating refractory HPV-positive malignancies (ClinicalTrials.gov: NCT02858310).

Other names

HPV16 E7-HLA-A*02:01 complexHPV16 E7 11-19 peptide-MHCE7 pMHCHuman papillomavirus 16 E7 antigenHPV16 E7-HLA complex

T-cell receptor (TCR) mediated recognition of the specific HPV16 E7 peptide (e.g., E7 11-19) in the groove of the HLA-A*02:01 molecule on the surface of tumor cells, triggering cytotoxic T-lymphocyte activation, secretion of perforin and granzymes, and targeted apoptosis of the HPV-positive cell (PubMed: 28350742).