Glycoprotein 100 (gp100) (gp100)

Glycoprotein 100 (gp100), also known as PMEL, is a type I transmembrane glycoprotein primarily expressed in melanocytes and highly overexpressed in melanoma (UniProt P40967). It plays a critical role in the maturation of melanosomes by forming the fibrous matrix necessary for melanin sequestration (PubMed: 11544038). In the context of cancer immunotherapy, gp100-derived peptides are processed and presented by Human Leukocyte Antigen (HLA) molecules, such as HLA-A1 or HLA-A2, on the surface of cells. When these peptides are presented by autologous dendritic cells, they act as potent stimuli for the activation and expansion of antigen-specific CD8+ cytotoxic T lymphocytes (PubMed: 9605929). This immune recognition leads to the targeted destruction of melanoma cells expressing the gp100 antigen. Therapeutic approaches targeting this complex include peptide-based vaccines and TCR-bispecific molecules like tebentafusp, which specifically binds the gp100 peptide-HLA-A*02:01 complex to redirect T cells (FDA: Kimmtrak Label). Common side effects of these therapies include vitiligo, resulting from the autoimmune destruction of healthy melanocytes that also express gp100. Clinical monitoring often involves assessing HLA-A2 status and gp100 expression levels in tumor biopsies to ensure patient eligibility.

Other names

PMELPMEL17SILVSilver locus protein homologMelanocyte protein PMELME20Melanocyte lineage-specific antigen GP100

Presentation of gp100-derived epitopes by HLA-A1 or HLA-A2 molecules to activate antigen-specific CD8+ T cells.