gp100 peptide–HLA-A*02:01 complex (gp100/HLA-A*02:01)

The gp100 peptide–HLA-A*02:01 complex is a specific peptide-major histocompatibility complex (pMHC) consisting of a fragment of the glycoprotein 100 (gp100, also known as PMEL17) presented by the Human Leukocyte Antigen (HLA) allele A*02:01. gp100 is a lineage-specific protein involved in the formation of melanosomes and is highly expressed in melanocytes and melanoma cells (UniProt P40967). In the context of cancer, these intracellular proteins are processed into short peptides and displayed on the cell surface by HLA molecules for recognition by T-cell receptors (TCRs). This specific complex is a validated therapeutic target for immunotherapies, most notably for the drug Tebentafusp, which is a bispecific protein that redirects T cells to kill gp100-expressing melanoma cells (FDA Label: Kimmtrak). Because HLA-A*02:01 is the most common HLA allele in many populations, this complex serves as a critical gateway for TCR-based interventions in both uveal and cutaneous melanoma. Therapeutic success depends on the patient possessing the HLA-A*02:01 genotype and the tumor expressing the gp100 protein (PubMed: 34554482).

Other names

PMEL peptide-MHC complexgp100(280-288)/HLA-A2gp100(209-217)/HLA-A2Melanocyte protein PMEL complexSilver locus protein homolog complexpMHC gp100:HLA-A*02:01

T-cell redirection via bispecific TCR-CD3 fusion, T-cell receptor binding, and immune-mediated cytotoxicity.