Human papillomavirus type 16 E6 and E7 oncoproteins presented on MHC class I (HPV16 E6/E7-MHC-I)

Human papillomavirus type 16 (HPV16) E6 and E7 are the primary oncoproteins responsible for the development and maintenance of HPV-associated malignancies, including cervical and oropharyngeal cancers (PMID: 29113301). These proteins function by inactivating key tumor suppressors; E6 promotes the ubiquitin-mediated degradation of p53, while E7 binds and neutralizes the retinoblastoma protein (pRb), collectively leading to uncontrolled cell proliferation and evasion of apoptosis (PMID: 30205116). Because these are viral proteins, they are processed into peptides and presented on the cell surface by Major Histocompatibility Complex (MHC) class I molecules, most commonly HLA-A*02:01, which allows them to be recognized by the immune system as non-self (PMID: 25108347). This peptide-MHC complex serves as a highly specific therapeutic target for TCR-engineered T-cell therapies and therapeutic vaccines, such as ISA101 and VGX-3100, which aim to induce or enhance a cytotoxic T-cell response against infected cells (PMID: 33024110). While these targets offer high specificity due to the absence of E6 and E7 in healthy human tissue, therapeutic challenges include tumor-mediated HLA downregulation and the highly immunosuppressive nature of the tumor microenvironment (PMID: 28603918).

Other names

HPV16 E6/E7 antigensHPV16 E6/E7 peptide-HLA complexesHPV16 E6/E7-MHC class I complexHPV16 E6/E7-HLA-A*02:01 complex

Recognition of the HPV16 E6 or E7 peptide-MHC class I complex by specific T-cell receptors (TCRs) to trigger cytotoxic T-lymphocyte (CTL) activation and subsequent lysis of tumor cells (PMID: 33024110).