Human leukocyte antigen A*24:02–glycoprotein 100-intron 4 peptide complex (HLA-A*24:02–gp100-in4)

The HLA-A*24:02–glycoprotein 100-intron 4 peptide complex is a specific peptide-major histocompatibility complex (pMHC) presented on the surface of melanoma cells. It consists of the HLA-A*24:02 molecule, a common MHC class I allele in East Asian populations, and a 9-amino acid peptide (VYFFLPDHL) derived from the fourth intron of the PMEL (gp100) gene (Robbins et al., 1997, Journal of Experimental Medicine). This intron-derived peptide is a neoantigen-like product of alternative splicing or incomplete mRNA processing, which occurs more frequently in malignant cells than in healthy tissues. The complex serves as a target for adoptive cellular therapies, particularly T-cell receptor (TCR) engineered T-cells, which are designed to recognize and kill cells presenting this specific antigen (Shichijo et al., 1998, International Journal of Cancer). Because gp100 is a lineage-specific protein, the complex is also found to a lesser extent in normal melanocytes, leading to potential safety concerns such as vitiligo or uveitis. Clinical interest in this target is high for treating HLA-A*24:02-positive patients with advanced melanoma, providing a personalized immunotherapy approach.

Other names

HLA-A*24:02–PMEL-in4HLA-A24-gp100-in4gp100-in4/HLA-A*24:02 complexVYFFLPDHL-HLA-A*24:02 complex

T-cell receptor (TCR) binding to the peptide-MHC complex, inducing cytotoxic T-lymphocyte (CTL) activation and targeted lysis of melanoma cells (Robbins et al., 1997, Journal of Experimental Medicine).