Melanocyte protein PMEL (gp100) peptide 209-217 (gp100:209-217)

The gp100:209-217 peptide is a specific 9-amino acid epitope derived from the melanocyte-lineage-specific protein PMEL (also known as gp100), which is highly expressed in most human melanomas (PubMed: 11210352). It is a well-characterized tumor-associated antigen that is presented to the immune system by the Human Leukocyte Antigen (HLA) A*02:01 allele. Because gp100 is largely restricted to melanocytes and melanoma cells, it serves as a precise target for cancer immunotherapy. Clinical strategies often utilize a modified version of this peptide, known as g209-2M (sequence IMDQVPFSV), which incorporates a methionine substitution at position 2 to enhance its binding affinity to the HLA molecule and improve its ability to stimulate CD8+ T cells (NIH: NCT00001625). In therapeutic contexts, the gp100:209-217 peptide is primarily used as a peptide vaccine to prime the patient's immune system against melanoma. Clinical trials have demonstrated that when this vaccine is administered alongside immune stimulants like Interleukin-2 or checkpoint inhibitors like Ipilimumab, it can significantly enhance objective response rates and progression-free survival in patients with advanced melanoma (PubMed: 21631324). However, the target is also associated with autoimmune side effects such as vitiligo, as the immune response can inadvertently target healthy pigment-producing cells. Monitoring for HLA-A*02:01 status is a prerequisite for patient selection for these peptide-based therapies.

Other names

gp100(209-217)g209-2MPMEL peptide 209-217Melanocyte-specific antigen gp100 fragmentSilver homolog peptidegp100:209-217(210M)

Induction of antigen-specific CD8+ cytotoxic T-lymphocyte (CTL) responses by presentation of the peptide epitope on HLA-A*02:01 molecules, resulting in the targeted destruction of melanoma cells expressing the gp100 protein.