Melanocyte protein PMEL-derived peptide epitopes presented on MHC class I (gp100/MHC I)

Melanocyte protein PMEL (gp100) is a lineage-specific glycoprotein involved in the formation of melanosomes within melanocytes (UniProt: P40967). In melanoma, gp100 is often overexpressed, and its degradation products are presented as peptide epitopes on the cell surface by Major Histocompatibility Complex (MHC) class I molecules, particularly HLA-A*02:01 (PubMed: 21631324). These peptide-MHC complexes are recognized by the T-cell receptor (TCR) of CD8+ cytotoxic T-lymphocytes, making them ideal targets for immunotherapy. Therapeutic interventions such as Tebentafusp, a bispecific TCR-anti-CD3 fusion protein, leverage this recognition to redirect T-cells to kill melanoma cells (FDA: Kimmtrak Prescribing Information). Additionally, gp100-derived peptide vaccines have been extensively studied to boost the body's natural immune response against tumors (PubMed: 21631324). However, because gp100 is also present in normal melanocytes in the skin, eye, and inner ear, targeting this complex can result in on-target off-tumor toxicities like vitiligo and uveitis (PubMed: 34534464).

Other names

gp100 peptide-MHC complexPMEL17-derived epitopesgp100:209-217gp100:280-288gp100:270-279Melanocyte protein PMEL epitopesPMEL

T-cell redirection and activation through bispecific T-cell receptor (TCR) fusion proteins or peptide-based vaccination to stimulate specific cytotoxic T-lymphocyte (CTL) responses (FDA: Kimmtrak; PubMed: 21631324).