Human papillomavirus type 18 E6 peptide-MHC class I complex (HPV-18 E6/MHC-I)

The Human papillomavirus type 18 (HPV-18) E6 peptide-MHC class I complex is a tumor-specific antigen found on the surface of cells infected with HPV-18 that have undergone malignant transformation [1, 4]. HPV-18 E6 is an early oncoprotein essential for viral replication and oncogenesis, primarily acting by inducing the ubiquitin-mediated degradation of the host tumor suppressor protein p53 [1]. In cancerous cells, processed fragments (epitopes) of the E6 protein are loaded onto Major Histocompatibility Complex (MHC) class I molecules and transported to the cell membrane [2]. This complex serves as a critical target for the adaptive immune system, specifically CD8+ cytotoxic T lymphocytes, which recognize the specific peptide-MHC (pMHC) combination via their T-cell receptors (TCRs) [2]. Because E6 expression is restricted to HPV-infected and transformed cells, it is considered an ideal target for immunotherapy, minimizing off-target effects on healthy tissues [4]. Therapeutic strategies targeting this complex include TCR-engineered T-cell therapies (e.g., KITE-439) and therapeutic vaccines (e.g., VGX-3100) designed to elicit a robust T-cell response against HPV-18 positive tumors such as cervical and oropharyngeal carcinomas [3, 4]. These therapies aim to overcome the immune evasion tactics of the virus, such as the downregulation of MHC molecules, to achieve durable clinical responses [2, 3].

Other names

HPV18 E6 peptide-HLA complexHPV-18 E6 oncoprotein epitopesHLA-presented HPV-18 E6 peptidesHPV-18 E6-specific pMHCHPV-18 E6/HLA-A*02:01 complex

T-cell receptor (TCR) mediated recognition and cytotoxic killing of tumor cells