gp100 peptide–HLA-A*0201 complex (gp100/HLA-A*02:01)

The gp100 peptide–HLA-A*0201 complex is a specific cell-surface antigen consisting of a peptide fragment derived from the glycoprotein 100 (gp100, also known as PMEL) protein presented by the Human Leukocyte Antigen (HLA) allele A*02:01. gp100 is a lineage-specific protein essential for the maturation of melanosomes and is highly overexpressed in both cutaneous and uveal melanoma cells (Nathan et al., 2021, NEJM). These complexes are recognized by the immune system as a signal for the presence of melanocytic cells, making them a prime target for T-cell-based immunotherapies. Drugs such as Tebentafusp, a bispecific gp100-directed T-cell receptor (TCR) fusion protein, specifically bind to these complexes to redirect T-cells to attack and lyse melanoma cells (Damato et al., 2023, J. Hematol. Oncol.). Because gp100 is also expressed in healthy melanocytes in the skin and eye, therapeutic targeting can lead to off-tumor toxicities like vitiligo and inflammatory skin reactions. This target is particularly clinically relevant in uveal melanoma, where it has provided a significant survival benefit for patients carrying the HLA-A*02:01 allele.

Other names

PMEL peptide-MHC complexgp100(280-288)/HLA-A2gp100:HLA-A*02:01Glycoprotein 100 peptide-HLA-A*0201 complexMelanocyte protein PMEL peptide-MHC

T-cell redirection via bispecific T-cell receptor (TCR) fusion protein (ImmTAC), which binds the gp100/HLA complex on tumor cells and recruits T-cells via an anti-CD3 effector domain.