HLA-A*02:01-restricted Premelanosome protein (gp100) peptide 280-288 (HLA-A*02:01/gp100:280-288)

The HLA-A*02:01-restricted PMEL/gp100:280-288 epitope is a specific peptide-major histocompatibility complex (pMHC) found on the surface of melanocytes and melanoma cells. It consists of the nine-amino acid peptide YLEPGPVTA, derived from the premelanosome protein (PMEL/gp100), presented by the HLA-A*02:01 allele (UniProt P17667). This complex serves as a critical target for immunotherapy, particularly in uveal and cutaneous melanoma, where gp100 is frequently overexpressed (PubMed: 11485911). Drugs like Tebentafusp, a bispecific T-cell engager, are designed to bind this pMHC with high affinity, redirecting T-cells to eliminate tumor cells (PubMed: 31548345). Because gp100 is also expressed in healthy melanocytes, treatment can lead to on-target, off-tumor effects such as vitiligo or skin rashes (FDA: Kimmtrak Label). Monitoring for HLA-A*02:01 status is essential for patient selection, as the therapy is only effective in individuals carrying this specific HLA type.

Other names

gp100:280-288YLEPGPVTA peptidePMEL:280-288HLA-A*02:01/PMELgp100(280)Melanocyte lineage-specific antigen gp100 epitope

T-cell redirection via bispecific T-cell engager (ImmTAC) or TCR-engineered T-cell therapy