Human papillomavirus type 16 E6 and E7 peptide-MHC class I complex (HPV16 E6/E7 pMHC)

Human papillomavirus type 16 (HPV16) E6 and E7 are constitutively expressed oncoproteins essential for the maintenance of the malignant phenotype in HPV-associated cancers (Hoppe-Seyler et al., 2018, PMID: 29115295). These proteins are processed intracellularly into short peptides and presented on the cell surface by Major Histocompatibility Complex (MHC) class I molecules, most notably HLA-A*02:01 (Draper et al., 2015, PMID: 26169152). This peptide-MHC (pMHC) complex serves as a highly specific target for the immune system, as these viral antigens are not expressed in healthy human tissues (Stevanović et al., 2015, PMID: 26249230). Therapeutic strategies targeting this complex include T-cell receptor (TCR) engineered T-cell therapies and bispecific molecules designed to redirect T-cells to kill HPV-positive tumor cells (Norberg et al., 2018, PMID: 29778621). Because E6 and E7 drive oncogenesis by inhibiting p53 and pRb respectively, their continued expression is required for tumor survival, making them ideal targets with a low risk of antigen loss (Moody & Laimins, 2010, PMID: 20651736). However, challenges include potential cross-reactivity with similar self-peptides and the downregulation of MHC molecules by tumors to evade immune detection (Garrido et al., 2016, PMID: 26514136).

Other names

HPV16 E6/E7-HLA complexHPV16 E6/E7 T-cell epitopesHPV16 E6/E7-MHC-IHPV16 E6/E7-derived peptides presented on MHC class I

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leads to the activation of cytotoxic T lymphocytes, which release perforins and granzymes to induce apoptosis in HPV-infected or transformed cells.