Human leukocyte antigen A*0201-presented glycoprotein 100 (280-288) epitope (gp100:280-288/HLA-A*0201)

The HLA-A*0201-presented gp100:280-288 epitope is a specific peptide-major histocompatibility complex (pMHC) that serves as a critical target for T-cell-based immunotherapies in melanoma. It consists of a nine-amino acid peptide (YLEPGPVTA) derived from the melanocyte-specific protein glycoprotein 100 (gp100), also known as PMEL, which is presented on the cell surface by the HLA-A*02:01 MHC Class I molecule (PubMed: 7507011). This epitope is highly expressed in both cutaneous and uveal melanoma cells, making it a viable target for redirecting the immune system against these tumors. The most prominent therapeutic targeting this complex is Tebentafusp, a bispecific fusion protein that links a high-affinity T-cell receptor (TCR) specific for this pMHC to an anti-CD3 effector domain (Kim et al., NEJM 2021). By binding to this epitope, the drug facilitates the formation of an immunological synapse between T-cells and melanoma cells, leading to tumor cell lysis. However, because gp100 is also expressed in healthy melanocytes, treatment can result in on-target, off-tumor toxicities such as skin rash and uveitis.

Other names

gp100(280-288) peptideYLEPGPVTA epitopePMEL:280-288HLA-A2 restricted gp100 epitopegp100:280-288

T-cell receptor (TCR) mediated recognition and redirection of T-cell cytotoxicity.