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

The gp100 peptide-HLA-A*0201 complex is a specific molecular target found on the surface of melanoma cells, consisting of a fragment of the melanocyte-specific protein gp100 (also known as PMEL) presented by the Human Leukocyte Antigen (HLA) allele A*0201 [PMID: 7507011]. gp100 is a glycoprotein involved in melanosome maturation and is highly expressed in both cutaneous and uveal melanoma [PMID: 10438932]. Because HLA-A*0201 is a common MHC class I allele, this specific peptide-MHC complex serves as a critical flag for the immune system to identify malignant melanocytes. Therapeutic strategies targeting this complex include bispecific T-cell engagers like Tebentafusp, which utilize a high-affinity T-cell receptor (TCR) to bind the gp100/HLA complex and an anti-CD3 domain to recruit effector T cells [PMID: 34551229]. This interaction bypasses the need for natural TCR recognition, leading to direct lysis of the tumor cells by redirected T lymphocytes. Clinical application is primarily focused on metastatic uveal melanoma, where it has demonstrated significant survival benefits in HLA-A*02:01-positive patients. However, because gp100 is also expressed in normal melanocytes, treatment can lead to on-target off-tumor effects such as skin rash and vitiligo [PMID: 35417605]. Monitoring for cytokine release syndrome is also essential during the initial stages of treatment with drugs targeting this complex.

Other names

PMEL peptide-HLA-A*0201 complexgp100:209-217/HLA-A*0201gp100:280-288/HLA-A*0201Melanocyte protein PMEL epitopegp100-MHC complex

T-cell redirection and activation via bispecific TCR-anti-CD3 fusion proteins or direct TCR recognition leading to cytotoxic T-lymphocyte mediated lysis of tumor cells [PMID: 34551229].