HLA-A*0201-presented NA17-A peptide epitope (NA17-A/HLA-A*0201)

The HLA-A*0201-presented NA17-A peptide epitope is a tumor-associated antigen complex consisting of the 9-amino acid peptide VLPDGVLPV bound to the HLA-A*0201 major histocompatibility complex (MHC) class I molecule. This specific peptide is derived from an unconventional source: an intronic sequence of the N-acetylglucosaminyltransferase V (GnT-V or MGAT5) gene that undergoes aberrant translation in melanoma cells (Guilloux et al., 1996, J Exp Med, 183:1173-83). Because this intronic sequence is not typically translated in normal tissues, the NA17-A epitope serves as a highly specific marker for malignant cells, particularly in melanoma patients (Moreau-Aubry et al., 2000, Cancer Res, 60:178-83). In the context of immunotherapy, this complex is a primary target for the development of T-cell receptor (TCR) engineered T-cell therapies and therapeutic cancer vaccines. CD8+ cytotoxic T lymphocytes (CTLs) recognize the NA17-A/HLA-A*0201 complex via their surface TCRs, which initiates a signaling cascade resulting in the targeted destruction of the cancer cell. While it offers a promising therapeutic window due to its restricted expression pattern, clinical challenges include the potential for tumor immune evasion through the loss of HLA expression and the necessity for precise TCR engineering to avoid cross-reactivity with similar peptides presented on healthy tissues.

Other names

NA17-A antigenVLPDGVLPV peptideGnT-V intron-derived peptideN-acetylglucosaminyltransferase V intron-encoded epitopeMelanoma antigen NA17-ANA17.A2

The peptide-MHC complex is recognized by the T-cell receptor (TCR) of CD8+ cytotoxic T lymphocytes, which triggers the release of perforins and granzymes, leading to the apoptosis of the target tumor cell.