Human leukocyte antigen A*02:01-restricted glycoprotein 100 peptide (209-217) (HLA-A*02:01/gp100(209-217))

The HLA-A*02:01-presented gp100:209-217 epitope is a specific peptide-major histocompatibility complex (pMHC) found on the surface of melanoma cells. It consists of a nine-amino acid fragment (ITDQVPFSV) derived from the glycoprotein 100 (gp100 or PMEL), a protein involved in melanosome maturation, which is presented by the HLA-A*02:01 allele (PMID: 10427028, 34614322). This complex serves as a critical target for cancer immunotherapies because gp100 is highly overexpressed in both cutaneous and uveal melanoma compared to normal tissues (PMID: 23550014). Drugs like Tebentafusp, a bispecific TCR-anti-CD3 fusion protein, specifically bind this pMHC to redirect T-cells to kill melanoma cells (PMID: 34551227). Therapeutic strategies also include peptide vaccines, often using a modified 'g209-2M' version of the peptide to enhance binding affinity and immunogenicity (PMID: 15150594). While effective, targeting this epitope can lead to inflammatory side effects in healthy melanocytes, resulting in conditions such as vitiligo or uveitis (PMID: 35235776).

Other names

gp100:209-217PMEL epitope 209-217ITDQVPFSV peptideg209HLA-A2/gp100(209-217)Melanocyte lineage-specific antigen gp100 epitope

T-cell redirection via bispecific T-cell receptor (TCR) fusion proteins, active immunization to induce peptide-specific CD8+ T-cell responses, and adoptive cell transfer of TCR-engineered T-cells.