Premelanosome protein (gp100) peptide ITDQVPFSV presented by HLA-A*02:01 (gp100:209-217/HLA-A*02:01)

The PMEL peptide ITDQVPFSV presented by HLA-A*02:01 is a specific peptide-major histocompatibility complex (pMHC) that serves as a critical target for melanoma immunotherapy (UniProt: P40967). PMEL, also known as gp100, is a lineage-specific glycoprotein involved in melanosome maturation and is highly expressed in melanocytes and melanoma cells (PubMed: 10426997). The ITDQVPFSV sequence represents a specific epitope (residues 209-217) that is processed and presented on the cell surface by the HLA-A*02:01 allele. This complex is recognized by specific T-cell receptors (TCRs), making it a focal point for developing TCR-based therapeutics like tebentafusp. Tebentafusp is a first-in-class bispecific TCR-anti-CD3 fusion protein that specifically binds to this pMHC complex to redirect T cells to kill melanoma cells (FDA: Kimmtrak Prescribing Information). Because gp100 is also expressed in normal melanocytes, treatment targeting this complex can lead to on-target off-tumor effects in the skin and eyes.

Other names

gp100:209-217PMEL:209-217HLA-A*02:01-gp100 complexMelanocyte-specific gp100 peptideITDQVPFSV-HLA-A*02:01gp100(209-217)

T-cell redirection via a bispecific T-cell receptor (TCR) fusion protein that binds the pMHC complex and the CD3 receptor on T cells (PubMed: 34554650).