Human leukocyte antigen A*02:01–gp100 peptide complex (HLA-A*02:01–gp100)

The HLA-A*02:01–gp100 peptide complex is a specific peptide-major histocompatibility complex (pMHC) presented on the surface of melanocytes and melanoma cells (Source [1, 2]). It comprises the HLA-A*02:01 molecule, a common MHC Class I allele, and a processed peptide fragment derived from the glycoprotein 100 (gp100) protein, also known as PMEL (Source [5, 11]). This complex serves as a critical recognition element for the immune system, allowing T-cell receptors (TCRs) to identify and eliminate cells expressing the gp100 antigen (Source [2, 12]). In the context of oncology, this complex is a validated therapeutic target, particularly for uveal melanoma, where gp100 is highly and consistently expressed (Source [1, 4]). Drugs such as tebentafusp, a first-in-class bispecific T-cell engager (ImmTAC), are engineered to bind this complex with extremely high affinity to redirect T-cell cytotoxicity toward tumor cells (Source [2, 5]). Because gp100 is also present in normal melanocytes, therapies targeting this complex often result in on-target, off-tumor toxicities like skin rash and vitiligo (Source [3, 9]). Clinical use of these therapies is strictly limited to patients who carry the HLA-A*02:01 allele, making HLA genotyping a mandatory biomarker for treatment eligibility (Source [7, 9]).

Other names

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

T-cell redirection via bispecific T-cell engagers that bind the peptide-MHC complex and CD3 on T cells