Human leukocyte antigen A*02:01 presenting glycoprotein 100 (280-288) epitope (HLA-A*02:01/gp100(280-288))

The HLA-A*02:01 presenting gp100 (280-288) epitope is a specific peptide-major histocompatibility complex (pMHC) that serves as a critical molecular target for immunotherapy in melanoma. The complex consists of the HLA-A*02:01 molecule, a common MHC class I allele, and a 9-amino acid peptide (YLEPGPVTA) derived from the glycoprotein 100 (gp100/PMEL) protein (UniProt: P40967). gp100 is a transmembrane glycoprotein primarily expressed in melanocytes and is highly overexpressed in melanoma cells (PubMed: 10426997). This pMHC complex is the specific target of tebentafusp (Kimmtrak), a first-in-class bispecific T-cell receptor (TCR) fusion protein approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma (FDA, 2022). By binding to this specific epitope, tebentafusp redirects T cells to lyse melanoma cells regardless of their endogenous TCR specificity. Therapeutic challenges include on-target, off-tumor toxicities such as vitiligo and skin rash due to gp100 expression in healthy melanocytes, as well as systemic cytokine release syndrome (Nathan et al., NEJM 2021).

Other names

HLA-A*02:01/gp100(280-288) complexgp100:280-288 peptide-MHC complexPMEL epitopeYLEPGPVTA-HLA-A*02:01gp100(280-288)

T-cell redirection via bispecific T-cell receptor (TCR) fusion proteins or activation of cytotoxic T lymphocytes through vaccination.