gp100 peptide–human leukocyte antigen complex (gp100–HLA complex)

The gp100 peptide–HLA complex consists of a peptide epitope derived from the gp100 protein, a melanocyte lineage antigen (also known as PMEL or melanoma antigen recognized by T cells 1), presented on the surface of cells by MHC molecules such as HLA-A*02:01 (MHC class I) or HLA-DR4 (MHC class II). This complex is essential for immune recognition of melanoma cells by cytotoxic T lymphocytes and is a validated target for various immunotherapeutic strategies, including TCR gene therapy, peptide vaccines, and T cell–engaging bispecific molecules such as tebentafusp. The most clinically relevant epitope is the nonamer YLEPGPVTA presented by HLA-A*02:01[8][9]. Recognition of this complex drives T cell activation and cytotoxicity against melanoma cells, making it central to both preclinical and approved therapies for melanoma. The structural and functional features of the gp100 peptide–HLA complex have also facilitated the design of altered peptide ligands to optimize therapeutic immune responses and improve the efficacy of cancer vaccines[6][7].

Other names

gp100/HLA-A*02:01 complexYLEPGPVTA–HLA-A*02:01 complexgp100 peptide–MHC complexHLA-DR4–gp100:44–59 complex

T cell redirection (Tebentafusp binds the gp100 peptide-HLA-A*02:01 complex on tumor cells and engages CD3 on T cells, triggering immune-mediated tumor cell killing) Cancer vaccine target (Altered peptide ligands and vaccines engage T cells to enhance anti-tumor immunity)