Human leukocyte antigen A*02:01 : Glycoprotein 100 (209-217) peptide complex (HLA-A*02:01:gp100(209-217))

The Human leukocyte antigen A*02:01 : Glycoprotein 100 (209-217) peptide complex is a specific peptide-major histocompatibility complex (pMHC) class I assembly that serves as a critical target in melanoma immunotherapy. It consists of the HLA-A*02:01 allele presenting a 9-amino acid fragment (ITDQVPFSV) derived from the glycoprotein 100 (gp100, also known as PMEL), a protein highly expressed in melanocytes and melanoma cells. This complex is recognized by the T-cell receptor (TCR) of cytotoxic CD8+ T cells, triggering an immune response against cells displaying the antigen. Because gp100 is a lineage-specific differentiation antigen, it is a primary target for therapeutic vaccines and engineered T-cell therapies, such as TCR-T cells. A modified version of the peptide, g209-2M (IMDQVPFSV), is frequently used in clinical trials to enhance binding affinity to the HLA molecule and improve immunogenicity. Therapeutic strategies targeting this complex have been extensively studied in cutaneous and uveal melanoma, often in combination with cytokines like IL-2 or checkpoint inhibitors. Notable safety concerns include on-target, off-tumor toxicities such as vitiligo and uveitis, which result from the immune-mediated destruction of healthy melanocytes in the skin and eyes.

Other names

HLA-A*02:01 : gp100_209–217 peptide complexHLA-A2:gp100(209-217)ITDQVPFSV:HLA-A*02:01IMDQVPFSV:HLA-A*02:01g209-2M:HLA-A*02:01Melanocyte protein PMEL (209-217) peptide-HLA-A*02:01 complex

The complex serves as a target for T-cell mediated immunotherapy. Peptide vaccines (e.g., g209-2M) provide the antigen to stimulate endogenous CD8+ T cells, while TCR-T therapies utilize engineered T cells expressing a TCR specific for this pMHC complex to induce tumor cell lysis. These therapies redirect the immune system to recognize and destroy cells expressing the gp100 protein in the context of HLA-A*02:01.