HLA-A*02:01-gp100 (209-217, 210M) peptide complex (HLA-A*02:01/gp100(210M))

The HLA-A*02:01 presenting gp100 209–217 210M peptide is a specific peptide-major histocompatibility complex (pMHC) that serves as a target for immunotherapy in melanoma. The gp100 protein, encoded by the PMEL gene, is a transmembrane glycoprotein involved in melanosome biogenesis and is highly expressed in melanocytes and melanoma cells (UniProt P40967). The 209-217 peptide sequence is a naturally occurring epitope; however, the 210M variant (IMDQVPFSV) is a synthetic, anchor-modified heteroclitic peptide where threonine is replaced by methionine at position 2 to increase binding affinity to the HLA-A*02:01 molecule (PubMed: 9633062). This increased stability enhances the activation of T-cells, making it a potent target for vaccines and T-cell receptor (TCR) based therapies. Tebentafusp (Kimmtrak) is a first-in-class bispecific protein that targets this specific pMHC complex to redirect T-cells to attack uveal melanoma cells (FDA: Kimmtrak Label). Clinical use of drugs targeting this complex requires patients to be HLA-A*02:01 positive, as the drug's efficacy is restricted to this specific MHC allele. Potential safety concerns include cytokine release syndrome and on-target off-tumor effects on healthy melanocytes in the skin and uvea.

Other names

gp100:209-217(210M) HLA-A2 complexIMDQVPFSV-HLA-A*02:01g209-2M peptide-MHC complexPMEL-HLA-A*02:01 complexgp100(209-217) 210M-HLA-A*02:01

T-cell receptor (TCR) mediated recognition and redirection of T-cells to target cells expressing the specific peptide-MHC complex.