Human papillomavirus type 16 E6 oncoprotein-derived peptides presented on MHC class I (HPV16 E6/MHC-I)

Human papillomavirus type 16 (HPV16) E6 oncoprotein-derived peptides presented on MHC class I molecules are critical targets for immunotherapy in HPV-associated cancers (UniProt P03126). The E6 protein is a primary viral oncogene that facilitates malignant transformation by targeting the p53 tumor suppressor for proteasomal degradation, thereby inhibiting apoptosis and promoting genomic instability (PubMed: 26351617). In infected cells, E6 is processed into short peptides, such as the immunodominant E6 29-38 epitope, which are then presented on the cell surface by MHC class I molecules, particularly HLA-A*02:01 (PubMed: 25833062). These complexes serve as highly specific markers for viral infection and oncogenic activity, as they are absent in healthy, non-infected human tissues. Therapeutic interventions targeting this complex include T-cell receptor (TCR) engineered T-cell therapies, such as KITE-439, which are designed to recognize and eliminate cells displaying these viral peptides (ClinicalTrials.gov: NCT03578406). Other modalities include therapeutic vaccines like ISA101 and fusion proteins like CUE-101, which aim to activate or expand the endogenous pool of E6-specific CD8+ T cells (PubMed: 32943572). The clinical utility of this target is primarily focused on treating advanced cervical, anal, and oropharyngeal squamous cell carcinomas. Challenges in targeting this complex include the potential for tumor immune escape through the downregulation of MHC class I expression. Additionally, ensuring the specificity of engineered TCRs is paramount to avoid cross-reactivity with similar self-peptides. Overall, the E6/MHC-I complex remains one of the most promising neoantigen targets for precision oncology in virus-driven malignancies.

Other names

HPV16 E6 peptide-HLA complexHPV16 E6 T-cell epitopeHPV16 E6/HLA-A*02:01 complexHuman papillomavirus 16 E6 antigen

Therapeutic agents target this complex by providing or eliciting T-cell receptors (TCRs) that specifically recognize the viral peptide in the context of MHC class I, leading to the selective destruction of HPV-infected or transformed cells.