Human leukocyte antigen A*02:01 presenting gp100 (280–288) peptide (HLA-A*02:01/gp100(280-288))

The HLA-A*02:01 presenting gp100 (280–288) peptide complex is a specific peptide-major histocompatibility complex (pMHC) expressed on the surface of melanocytes and melanoma cells (PMID: 35081293). The gp100 protein, also known as PMEL, is a transmembrane glycoprotein essential for the formation of stage II melanosomes (UniProt: P40967). The specific epitope spanning amino acids 280–288 (sequence: YLEPGPVTA) is a highly immunogenic peptide presented by the HLA-A*02:01 allele, making it a prime target for T-cell receptor (TCR) based therapies (PMID: 23838270). Tebentafusp (Kimmtrak) is a first-in-class bispecific T-cell engager that targets this complex to treat metastatic uveal melanoma in HLA-A*02:01-positive patients (FDA, 2022). By binding both the pMHC on tumor cells and the CD3 receptor on T-cells, these therapies induce direct cytotoxic activity against the cancer (PMID: 35081293). However, because gp100 is also expressed in normal melanocytes, safety concerns include on-target off-tumor toxicities such as skin rashes and pigment changes (PMID: 31512061). Therapeutic efficacy is strictly dependent on the patient's HLA genotype, as the drug only recognizes the peptide when presented by the A*02:01 isoform.

Other names

HLA-A*02:01/YLEPGPVTAgp100:280-288/HLA-A2 complexMHC-peptide complex HLA-A*02:01:gp100_280-288gp100 peptide-HLA-A*02:01

T-cell redirection via bispecific T-cell receptor (TCR) fusion protein binding to the peptide-MHC complex and CD3 on T-cells.