HLA-A*02:01-restricted gp100 peptide (209-217) complex (HLA-A*02:01/gp100(209-217))

The HLA-A*02:01-restricted gp100 (209-217) complex is a specific peptide-major histocompatibility complex (pMHC) that serves as a critical target for cancer immunotherapy, particularly in melanoma. Gp100, also known as PMEL, is a melanocyte-differentiation antigen highly expressed in melanocytes and melanoma cells. The specific epitope spanning amino acids 209-217 is processed and presented on the cell surface by the HLA-A*02:01 allele, making it recognizable by CD8+ T-cell receptors (TCRs). Because HLA-A*02:01 is a prevalent allele in many populations, this complex is a widely studied target for vaccines and TCR-based therapies. Tebentafusp, a first-in-class bispecific T-cell engager, specifically binds this pMHC complex to redirect T cells to kill melanoma cells. Therapeutic engagement of this target can lead to significant clinical responses in uveal melanoma, which historically had limited treatment options. However, targeting this complex is often associated with immune-related adverse events like cytokine release syndrome and skin-related toxicities due to gp100 expression in normal melanocytes.

Other names

gp100:209-217g209-2MPMEL:209-217HLA-A2/gp100 complexMelanocyte protein PMEL peptide 209-217ITDQVPFSV peptideIMDQVPFSV peptide

T-cell redirection via bispecific T-cell engagers (TCR-CD3 fusion) or active immunization to induce peptide-specific cytotoxic T-lymphocyte responses.