Glycoprotein 100 peptide–human leukocyte antigen A*02:01 complex (gp100-HLA-A*02:01 complex)

The gp100-HLA-A*02:01 complex is a molecular structure formed when a peptide fragment derived from glycoprotein 100 (gp100, a melanoma-associated antigen) is presented on the surface of cells by the human leukocyte antigen A*02:01 (HLA-A*02:01), a major histocompatibility complex (MHC) class I molecule. This complex is recognized by certain T cells and by engineered immune-recruiting agents such as tebentafusp. Targeting the gp100-HLA-A*02:01 complex allows for specific immune recognition and destruction of cancer cells, particularly in uveal melanoma, while sparing cells that do not display this complex. The interaction forms the basis for a class of bispecific molecules that re-direct T lymphocytes to kill tumor cells by linking the T cell CD3 receptor to the tumor-specific complex. Eligibility for such therapies requires both tumor expression of gp100 and a positive HLA-A*02:01 genotype.

Other names

gp100/HLA-A*02:01gp100 pHLA complexgp100-derived peptide–HLA-A*02:01YLEPGPVTA-HLA-A*02:01 complex

T cell–redirecting engagement: Tebentafusp binds to the gp100-HLA-A*02:01 complex on melanoma cells and recruits/activates cytotoxic T cells via CD3 engagement, leading to immune-mediated killing of the melanoma cell.