Melanocyte protein PMEL peptide–HLA-A*02:01 complex (gp100-HLA-A2) (gp100-HLA-A2)

The Melanocyte protein PMEL peptide–HLA-A*02:01 complex (gp100-HLA-A2) is a specific molecular target formed by the presentation of a peptide derived from the melanocyte-differentiation antigen gp100 (also known as PMEL) by the Human Leukocyte Antigen (HLA) allele A*02:01 [1]. This complex is highly expressed on the surface of melanoma cells, including uveal and cutaneous melanoma, making it a critical target for T-cell-mediated immunotherapy [3]. The recognition of this complex by T-cell receptors (TCRs) triggers an immune response against the tumor cells. Therapeutic intervention, such as the bispecific fusion protein Tebentafusp, utilizes a high-affinity TCR domain to bind the gp100-HLA complex and an anti-CD3 domain to recruit and activate polyclonal T cells [2]. This redirection of T cells bypasses the need for natural TCR recognition, leading to the direct lysis of melanoma cells [4]. However, because gp100 is also expressed in normal melanocytes, treatment can lead to off-tumor side effects like skin toxicity and systemic cytokine release [2, 3].

Other names

gp100-MHC complexPMEL-HLA-A*02:01Melanocyte protein PMEL peptide-MHCgp100 antigenSilver locus protein homologgp100-HLA-A2

Tebentafusp is a bispecific gp100 peptide-HLA-directed T-cell receptor fusion protein that redirects T cells to target and lyse gp100-expressing tumor cells via the CD3 receptor [2, 3].