HLA-A*02:01-gp100(209-217) complex (HLA-A*02:01/gp100(209-217))

The HLA-A*02:01-gp100(209-217) complex is a specific peptide-major histocompatibility complex (pMHC) class I molecule that serves as a critical therapeutic target in immuno-oncology [1, 4]. It consists of the HLA-A*02:01 allele presenting a 9-amino acid peptide derived from the melanocyte-specific protein gp100, also known as PMEL [3, 13]. This complex is predominantly expressed on the surface of uveal and cutaneous melanoma cells, as well as normal melanocytes [1, 10]. The biological function of this complex is to present intracellular antigens to the immune system for recognition by CD8+ T-cells via their T-cell receptors (TCRs) [14, 17]. Tebentafusp, the first FDA-approved bispecific T-cell engager for solid tumors, specifically targets this pMHC complex to redirect and activate polyclonal T-cells against melanoma cells [5, 8]. Because the target is HLA-restricted, therapeutic efficacy is limited to patients with the HLA-A*02:01 genotype [10, 15]. Common safety concerns associated with targeting this complex include cytokine release syndrome and on-target, off-tumor skin toxicities due to the presence of gp100 on healthy melanocytes [1, 20].

Other names

HLA-A2/gp100(209-217)HLA-A*02:01-ITDQVPFSVHLA-A*02:01-IMDQVPFSVgp100:209-217 peptide-MHC complexPMEL:209-217/HLA-A*02:01gp100(209-217)-HLA-A*02:01

T-cell redirection and activation through bispecific T-cell receptor (TCR) engagement with the peptide-MHC complex