HLA-A*02:01-presented gp100 peptide (280-288) (HLA-A2/gp100(280-288))

The MHC class I presenting gp100:280-288 complex is a specific peptide-major histocompatibility complex (pMHC) found on the surface of melanocytes and melanoma cells. The gp100 protein, also known as PMEL or silver locus protein, is a lineage-specific antigen involved in the formation of melanosomes (UniProt P40967). The 280-288 epitope (sequence: YLEPGPVTA) is processed and presented by the HLA-A*02:01 allele, serving as a critical recognition site for the immune system (Kawakami et al., 1995, PMID: 7538026). Altered peptide variants, such as the 280-288(9V) heteroclitic peptide (YLEPGPVTV), are frequently utilized in therapeutic vaccines to enhance binding affinity to the HLA molecule and improve the activation of tumor-reactive T cells (Parkhurst et al., 1996, PMID: 8671470). This pMHC complex is the primary target for tebentafusp, a first-in-class bispecific T-cell engager (Immune Mobilizing Monoclonal TCR Against Cancer, ImmTAC) approved for the treatment of HLA-A*02:01-positive patients with unresectable or metastatic uveal melanoma (Nathan et al., 2021, PMID: 34551229). Because gp100 is expressed in normal melanocytes, therapies targeting this complex can lead to on-target off-tumor toxicities in the skin and eyes.

Other names

gp100:280-288PMEL:280-288HLA-A*02:01-YLEPGPVTAgp100(280-288) altered peptide ligandgp100:280-288(9V)YLEPGPVTVMelanocyte protein PMEL peptide-MHC complex

T-cell redirection via bispecific TCR-anti-CD3 fusion protein; Active immunization to induce peptide-specific cytotoxic T lymphocytes