Human leukocyte antigen A*02:01 presenting the gp100 (PMEL) 209–217 epitope (HLA-A*02:01/gp100(209-217))

The HLA-A*02:01 presenting the gp100/PMEL 209–217 epitope is a specific peptide-major histocompatibility complex (pMHC) found on the surface of melanocytes and melanoma cells (UniProt P40967). The gp100 protein, also known as PMEL, is a lineage-specific antigen involved in melanosome biogenesis, and its 209–217 peptide fragment (ITDQVPFSV) is processed and presented by the HLA-A*02:01 allele to CD8+ T-cells (PubMed: 10449770). This complex serves as a critical target for cancer immunotherapy, particularly in patients with uveal and cutaneous melanoma who are HLA-A*02:01 positive (PubMed: 34554662). Therapeutic strategies targeting this pMHC include bispecific T-cell engagers like tebentafusp, which utilize a high-affinity T-cell receptor (TCR) to recognize the complex and a CD3 effector domain to activate polyclonal T-cells against the tumor (FDA: Kimmtrak Label). Because gp100 is also expressed in normal melanocytes, treatment can lead to on-target, off-tumor effects such as vitiligo or skin rashes (PubMed: 30135175). Monitoring for cytokine release syndrome is essential during the administration of drugs targeting this complex (PubMed: 34554662).

Other names

HLA-A*02:01/PMEL(209-217)HLA-A2/gp100(209-217)gp100:209-217 peptide-MHC complexITDQVPFSV-HLA-A*02:01PMEL209-217/HLA-A*02:01

Bispecific T-cell engager (ImmTAC) consisting of a high-affinity T-cell receptor (TCR) fused to an anti-CD3 single-chain variable fragment (scFv), which redirects T-cells to recognize and kill cells presenting the specific peptide-MHC complex.