Melanocyte protein PMEL (gp100) peptide-HLA-A*0201 complex (gp100/HLA-A*0201)

The gp100-derived HLA-A*0201-restricted epitope is a peptide-major histocompatibility complex (pMHC) presented on the surface of cells, consisting of a specific peptide fragment from the Melanocyte protein PMEL (also known as gp100) bound to the Human Leukocyte Antigen (HLA) allele A*02:01 (UniProt, 2024). This epitope is a primary target in melanoma immunotherapy because gp100 is highly overexpressed in malignant melanoma cells compared to most normal tissues (PubMed, 2021). In healthy individuals, gp100 expression is primarily restricted to melanocytes in the skin, eye, and inner ear, where it plays a critical role in the formation of melanosomes (NCBI, 2023). Therapeutic strategies targeting this epitope include tebentafusp, a first-in-class bispecific T-cell engager that redirects T cells to kill gp100-expressing tumor cells by binding the pMHC with high affinity (FDA, 2022). Additionally, peptide vaccines such as gp100:209-217(210M) have been developed to stimulate endogenous T-cell responses against this specific complex (Journal of Clinical Oncology, 2011). Because the target is restricted to the HLA-A*02:01 allele, patient selection via genetic typing is mandatory for these therapies (Nathan et al., 2021). Safety concerns often involve on-target off-tumor effects, such as vitiligo and skin rashes, resulting from the destruction of healthy melanocytes (StatPearls, 2023).

Other names

gp100:209-217gp100:280-288gp100:154-162PMEL-derived HLA-A2 epitopegp100-MHC complexgp100 peptide-HLA-A*02:01

Binding of a soluble T-cell receptor (TCR) to the peptide-MHC complex, which then recruits T cells via an anti-CD3 effector domain to induce tumor cell lysis.