gp100-derived melanoma peptide-HLA-A*0201 complex (gp100/HLA-A*0201)

The gp100-derived melanoma peptide-HLA-A*0201 complex is a specific immunological target composed of peptides from the melanocyte protein PMEL (gp100) bound to the MHC Class I molecule HLA-A*0201 (UniProt: P40967). gp100 is a lineage-specific protein essential for the formation of melanosomes and is overexpressed in the majority of melanomas, making it a prominent tumor-associated antigen (PubMed: 11544351). When presented on the surface of autologous dendritic cells or tumor cells, these peptides are recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, triggering an immune response aimed at eliminating cells expressing the antigen. Therapeutic interventions, such as the bispecific TCR-anti-CD3 fusion protein tebentafusp, specifically bind this complex to redirect T cells to kill melanoma cells in HLA-A*02:01-positive patients (FDA: Kimmtrak). However, because gp100 is also expressed in normal melanocytes, treatment can result in on-target off-tumor toxicities like vitiligo or ocular inflammation (StatPearls: Melanoma Management). This target represents a cornerstone of peptide-based and cellular immunotherapy strategies for metastatic melanoma.

Other names

PMEL peptide-MHC complexgp100:HLA-A*02:01Melanocyte protein PMEL antigengp100(209-217) peptideg209-2M peptide complex

Activation of antigen-specific CD8+ T cells through T-cell receptor (TCR) recognition of the peptide-MHC complex, leading to targeted lysis of melanoma cells.