Melanocyte protein PMEL (gp100) peptide-MHC class I complex (gp100-MHC)

The gp100 antigen, also known as Melanocyte protein PMEL, is a type I transmembrane glycoprotein primarily involved in the organization of melanosomes in melanocytes (UniProt P40967). In the context of oncology, gp100 is a well-characterized tumor-associated antigen (TAA) that is highly expressed in melanoma cells, including both cutaneous and uveal subtypes (Nathan et al., 2021). The therapeutic target is specifically the processed gp100 peptide (such as the gp100:209-217 epitope) presented on the cell surface by Major Histocompatibility Complex (MHC) Class I molecules, most commonly HLA-A*02:01 (Middleton et al., 2020). This peptide-MHC complex is recognized by T-cell receptors (TCRs), making it a prime candidate for TCR-based immunotherapies. Drugs like Tebentafusp, a bispecific gp100-peptide-HLA-directed T-cell engager, bind this complex with high affinity to redirect T-cell-mediated cytotoxicity against melanoma cells (FDA, 2022). Because gp100 is also expressed in healthy melanocytes, treatment often results in on-target, off-tumor effects such as vitiligo and skin rashes (Damato et al., 2023).

Other names

PMELPMEL17Silver locus protein homologgp100:209-217 peptide-HLA-A*02:01 complexMelanoma-associated antigen gp100ME20-M

T-cell redirection via a bispecific molecule consisting of a soluble T-cell receptor (TCR) fused to an anti-CD3 effector domain, which facilitates the formation of an immunological synapse between cytotoxic T cells and gp100-expressing tumor cells.