Melanocyte protein PMEL peptide (YLEPGPVTV) presented by HLA-A*02:01 (gp100(280-288)/HLA-A*02:01)

The Melanocyte protein PMEL peptide (YLEPGPVTV) presented by HLA-A*02:01 is a specific peptide-major histocompatibility complex (pMHC) that serves as a therapeutic target in oncology, particularly for melanoma. PMEL, commonly known as gp100, is a transmembrane glycoprotein essential for the maturation of melanosomes in melanocytes (UniProt: P40967). The YLEPGPVTV epitope, corresponding to residues 280-288 of the gp100 protein, is processed and displayed on the cell surface by the HLA-A*02:01 molecule, a common Class I Human Leukocyte Antigen (PubMed: 22561687). This pMHC complex is highly expressed in uveal and cutaneous melanoma cells, making it an ideal target for T-cell receptor (TCR)-based therapies. The drug tebentafusp is a first-in-class bispecific protein that binds this specific complex with high affinity through its TCR domain while recruiting T cells via an anti-CD3 domain (FDA: Kimmtrak Label). Because gp100 is also present in healthy melanocytes in the skin, eye, and ear, targeting this complex can lead to on-target, off-tumor toxicities such as vitiligo and rash (PubMed: 34551227). Clinical efficacy is strictly dependent on the patient's HLA-A*02:01 genotype, which acts as a mandatory companion diagnostic biomarker.

Other names

gp100 peptide (280-288)PMEL peptide (280-288)gp100:280-288YLEPGPVTV-HLA-A2 complexMelanocyte protein PMEL (280-288)

T-cell redirection and activation via a bispecific T-cell receptor (TCR)-anti-CD3 fusion protein