Human leukocyte antigen A*02:01 presenting glycoprotein 100 peptide (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 cells, particularly melanocytes and melanoma cells (UniProt P40967, P01892). HLA-A*02:01 is a highly prevalent Class I human leukocyte antigen allele that presents endogenous peptides to CD8+ T cells (PubMed: 22561687). Glycoprotein 100 (gp100), also known as PMEL, is a protein essential for melanosome biogenesis and is highly expressed in melanoma (PubMed: 34554662). The specific peptide often targeted within this complex is the gp100(280-288) epitope, YLEPGPVTA (FDA: Kimmtrak Label). This complex serves as a critical therapeutic target for TCR-bispecific molecules like tebentafusp, which redirects T-cell activity against melanoma cells (NEJM: 10.1056/NEJMoa2103483). Because gp100 is also expressed in normal melanocytes, targeting this complex can lead to on-target, off-tumor effects such as skin toxicity and cytokine release syndrome (EMA: Kimmtrak EPAR). This target represents a significant advancement in the treatment of HLA-A*02:01-positive patients with metastatic uveal melanoma.

Other names

HLA-A2/gp100HLA-A*02:01/PMELgp100:280-288/HLA-A2 complexMHC-gp100 complexPMEL17/HLA-A*02:01gp100 peptide-MHC complex

Bispecific T-cell redirection via a high-affinity T-cell receptor (TCR) fused to an anti-CD3 effector domain