gp100 peptide YLEPGPVTA-HLA-A*02:01 complex (gp100:HLA-A*02:01)

The gp100:YLEPGPVTA-HLA-A*02:01 peptide-MHC complex is a specific molecular target consisting of a 9-amino acid peptide derived from the glycoprotein 100 (gp100) protein presented by the Human Leukocyte Antigen (HLA) allele A*02:01. Gp100, also known as PMEL, is a lineage-specific protein involved in the formation of melanosomes and is highly expressed in melanocytes and melanoma cells (UniProt P17667). This specific peptide-MHC (pMHC) complex serves as a crucial epitope for immune recognition by T-cell receptors (TCRs). In the context of cancer immunotherapy, this complex is the primary target for Tebentafusp, a first-in-class bispecific T-cell engager known as an ImmTAC (Immune mobilizing monoclonal TCR Against Cancer). Tebentafusp utilizes a high-affinity TCR domain to bind the gp100:HLA-A*02:01 complex on tumor cells and an anti-CD3 domain to recruit and activate polyclonal T-cells, leading to direct tumor cell lysis (Nathan et al., NEJM 2021). This target is particularly significant in uveal melanoma, where it has provided a breakthrough therapeutic option for patients carrying the HLA-A*02:01 allele.

Other names

gp100(280-288) peptide-HLA-A*02:01 complexPMEL:YLEPGPVTA-HLA-A*02:01gp100-A2 complexgp100 peptide-MHC complex

T-cell redirection via a bispecific T-cell engager (ImmTAC) that binds the peptide-MHC complex with high affinity and recruits T-cells via CD3 binding.