T cell receptor specific for NA17-A peptide presented by HLA-A*02:01 (NA17-A TCR)

The T cell receptor (TCR) on NA17.A2-specific CD8+ T cells is a specialized immune receptor that recognizes the NA17-A antigen, a peptide derived from an intron of the N-acetylglucosaminyltransferase V (GnT-V or MGAT5) gene. This TCR specifically binds to the nonapeptide VLPDVFIRC when it is presented by the Human Leukocyte Antigen (HLA)-A*02:01 molecule on the surface of cells. NA17-A is a tumor-associated antigen (TAA) that is frequently overexpressed in melanoma due to the activation of a cryptic promoter, but it is not expressed at significant levels in normal adult tissues. The interaction between this TCR and the NA17-A/HLA-A2 complex triggers the activation of cytotoxic CD8+ T cells, leading to the release of effector molecules like interferon-gamma and granzymes that destroy the target tumor cells. In therapeutic development, this TCR is a key component of TCR-engineered T cell (TCR-T) therapies and has been the focus of clinical trials involving peptide-pulsed dendritic cell vaccines. Monitoring for this TCR and its cognate antigen is essential for patient selection in personalized immunotherapy for metastatic melanoma.

Other names

NA17-A-specific T cell receptorGnT-V-specific T cell receptorN-acetylglucosaminyltransferase V-specific TCRVLPDVFIRC-specific TCRNA17.A2-specific TCRNA17-A2 TCR

The TCR specifically recognizes the NA17-A peptide (VLPDVFIRC) presented by HLA-A*02:01 on the surface of tumor cells. Upon binding, the TCR-CD3 complex initiates intracellular signaling through ITAM phosphorylation, leading to T cell proliferation, cytokine production (e.g., IFN-gamma), and directed lysis of the target cell via perforin and granzymes.