Melanocyte protein PMEL peptide–HLA-A*02:01 complex (gp100–HLA-A*02:01)

The gp100-derived peptide–HLA-A*02:01 complex is a specific peptide-major histocompatibility complex (pMHC) presented on the surface of melanocytes and melanoma cells. It consists of a processed fragment of the melanocyte-specific protein PMEL (also known as gp100) bound to the human leukocyte antigen (HLA) allele A*02:01 (UniProt P40967). This complex serves as a critical target for cancer immunotherapy, particularly in patients with uveal melanoma. The therapeutic relevance of this target is highlighted by tebentafusp, a first-in-class bispecific T-cell engager that utilizes a high-affinity T-cell receptor (TCR) domain to recognize this specific pMHC and an anti-CD3 domain to recruit T cells (FDA, 2022). Because gp100 is also expressed in normal melanocytes, targeting this complex can lead to on-target, off-tumor toxicities such as vitiligo or rash (Nathan et al., 2021; PubMed PMID: 34551229). Its clinical application is restricted to patients who carry the HLA-A*02:01 allele, making HLA typing a prerequisite for therapy. The complex is a key mediator in the immune system's ability to recognize and destroy malignant melanocytes.

Other names

gp100 peptide–HLA-A*02:01 complexPMEL–HLA-A*02:01gp100:209-217–HLA-A*02:01gp100:280-288–HLA-A*02:01Melanoma-associated antigen gp100–MHC complex

T-cell redirection via bispecific T-cell engagers or activation of antigen-specific T-cells via peptide vaccination.