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Human leukocyte antigen A*02:01–Human papillomavirus type 16 E6 (29-38) peptide complex (HLA-A*02:01–HPV16 E6 (29-38))

Target
HLA-A*02:01–HPV16 E6 (29-38)
Molecular classification
MHC class I protein complex, Antigen-presenting molecule, Peptide-MHC complex
01

Overview

The HLA-A*02:01–HPV16 E6 (29-38) peptide complex is a specific molecular target consisting of the Human Leukocyte Antigen (HLA) allele A*02:01 and a 10-amino acid epitope (TIHDIILECV) derived from the E6 oncoprotein of Human Papillomavirus type 16 (HPV16) [PMID: 32814747]. This complex is expressed on the surface of cells infected with HPV16 or transformed into malignant cells, serving as a critical signal for the adaptive immune system to recognize "non-self" viral antigens [PMID: 31515461]. In the context of cancer, the E6 protein is a primary driver of oncogenesis by facilitating the degradation of the p53 tumor suppressor protein, making this specific peptide-MHC (pMHC) complex an ideal tumor-specific target [PMID: 28923934]. Therapeutic interventions, such as TCR-engineered T-cell therapies and bispecific T-cell engagers, are designed to selectively bind this complex to trigger a potent cytotoxic T-cell response against HPV-associated malignancies like cervical and oropharyngeal cancers [PMID: 35110346]. Because the target is highly specific to HPV-infected cells, it offers a narrow therapeutic window aimed at minimizing damage to healthy tissues, although challenges such as HLA downregulation and potential cross-reactivity with similar human peptides remain significant considerations in drug development [PMID: 33461155].

Other names
HLA-A*02:01/HPV16 E6(29-38)MHC-HPV16 E6 complexpMHC complex (HPV16 E6 29-38)HLA-A2-E6(29-38)HLA-A*02:01-TIHDIILECV complex
02

Mechanism of action

Targeting of the peptide-MHC complex by engineered T-cell receptors (TCRs) or TCR-mimetic molecules to induce T-cell mediated lysis of HPV16-positive tumor cells.

03

Biological functions

Antigen presentationImmune responseT-cell activationCytotoxic T-cell recognition
04

Disease associations

Cervical cancerHead and neck squamous cell carcinomaAnal cancerVulvar cancerPenile cancerInfection (Human papillomavirus)
05

Safety considerations

Off-target cross-reactivity with self-peptidesCytokine release syndrome (CRS)On-target off-tumor toxicityImmune evasion via HLA downregulation
06

Interacting drugs

IMC-E6

3 more in the full profile.

07

Biomarkers

HLA-A*02:01 genotypeHPV16 DNA/RNA positivityE6 oncoprotein expressionT-cell receptor (TCR) clonality

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