Melanocyte protein PMEL (gp100) peptide 209-217 presented by Human Leukocyte Antigen A*02:01 (gp100(209-217)/HLA-A*02:01)

The gp100 209–217 peptide bound to HLA-A*02:01 is a peptide-major histocompatibility complex (pMHC) that serves as a critical target for melanoma immunotherapy. The peptide is derived from the melanocyte differentiation antigen gp100 (also known as PMEL or SILV), which is highly expressed in both cutaneous and uveal melanoma cells (1.2.2, 1.4.1). When presented by the HLA-A*02:01 molecule, this specific epitope (sequence ITDQVPFSV) can be recognized by the T-cell receptors (TCRs) of cytotoxic CD8+ T lymphocytes, leading to an anti-tumor immune response (1.1.2, 1.3.1). A modified version of the peptide, gp100:209-217(210M), features a threonine-to-methionine substitution that enhances its binding affinity to HLA-A*02:01, making it a potent component of therapeutic cancer vaccines (1.1.3, 1.4.5). Beyond vaccines, this pMHC complex is a target for advanced cellular therapies, including TCR-engineered T cells (TCR-T) and TCR-like chimeric antigen receptor T cells (TCRm-CAR-T), which are designed to overcome natural immune tolerance (2.1.3, 2.4.4). Clinical challenges associated with targeting this complex include on-target off-tumor toxicities, such as vitiligo and skin rash, resulting from the presence of gp100 in normal melanocytes (1.3.2, 1.3.4).

Other names

gp100(209-217)-HLA-A2 complexPMEL(209-217)-HLA-A*02:01ITDQVPFSV-HLA-A*02:01IMDQVPFSV-HLA-A*02:01g209-2Mgp100:209-217(210M)Pmel17(209-217)/HLA-A*02:01

The target functions as a specific epitope for T-cell recognition; drugs targeting this complex either stimulate the expansion of endogenous antigen-specific CD8+ T cells (vaccines) or utilize engineered receptors (TCR-T or TCRm-CAR-T) to directly bind the peptide-MHC complex and trigger T-cell mediated cytotoxicity against tumor cells (1.4.1, 2.1.3, 2.4.4).