Human papillomavirus-derived antigenic peptides presented on human leukocyte antigen class I (HPV-HLA-I) (HPV-HLA-I)

Human papillomavirus (HPV)-derived antigenic peptides presented on human leukocyte antigen (HLA) class I molecules are critical targets for the immunotherapy of HPV-associated malignancies, such as cervical and oropharyngeal cancers. These complexes consist of short peptide fragments, predominantly from the viral oncoproteins E6 and E7, which are processed and displayed on the cell surface by HLA class I molecules (Stevanović et al., 2015). The recognition of these peptide-MHC (pMHC) complexes by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes is essential for the immune-mediated destruction of virally transformed cells (National Cancer Institute, 2023). Since E6 and E7 expression is restricted to HPV-infected and cancerous cells, these pMHC complexes serve as highly specific tumor-associated antigens (Draper et al., 2015). Therapeutic strategies targeting this complex include TCR-engineered T-cell (TCR-T) therapies, therapeutic vaccines, and bispecific molecules like ImmTACs (Cue Biopharma, 2024). However, clinical challenges include tumor-mediated HLA downregulation and the potential for off-target toxicity due to TCR cross-reactivity with similar self-peptides (PubMed, 2022).

Other names

HPV E6/E7 pMHCHPV-specific peptide-HLA complexesHPV-HLA-A*02:01 complexesHPV-derived T-cell epitopesHPV-specific pMHC

T-cell receptor binding, T-cell activation, and cytotoxic T lymphocyte-mediated lysis