gp100 peptide (YLEPGPVTA) presented by HLA-A*02:01 (gp100/HLA-A*02:01)

The gp100 peptide (YLEPGPVTA) presented by HLA-A*02:01 is a specific peptide-major histocompatibility complex (pMHC) target found on the surface of melanocytes and melanoma cells (UniProt P40967). The peptide is derived from the glycoprotein 100 (gp100), also known as PMEL, which is a protein involved in the maturation of melanosomes. This specific epitope, spanning amino acids 280 to 288, is processed intracellularly and presented by the HLA-A*02:01 allele, a common MHC class I molecule. This complex is a validated therapeutic target for T-cell redirection therapies, such as the bispecific fusion protein tebentafusp (FDA Kimmtrak Label, 2022). Tebentafusp binds the pMHC with high affinity via a TCR domain and recruits T-cells through a CD3-binding domain to induce tumor cell lysis (Nathan et al., 2021, NEJM). Because gp100 is a lineage-specific antigen, it is expressed in both malignant melanoma cells and healthy melanocytes. Consequently, therapies targeting this complex can cause on-target, off-tumor toxicities, including skin-related adverse events and cytokine release syndrome. This target is particularly significant in uveal melanoma, where traditional checkpoint inhibitors have shown limited efficacy.

Other names

gp100(280-288)/HLA-A*02:01PMEL peptide/HLA-A*02:01gp100:280-288YLEPGPVTA-HLA-A2 complex

T-cell redirection and activation via bispecific T-cell receptor (TCR) fusion protein