HLA-A*02:01-presented gp100 peptide epitopes (HLA-A*02:01/gp100)

The target consists of specific peptide fragments derived from the gp100 protein (also known as PMEL) presented by the HLA-A*02:01 molecule. gp100 is a transmembrane glycoprotein primarily expressed in melanocytes and is highly overexpressed in melanoma (UniProt P40967). The epitopes gp100:209-217 and gp100:280-288 are processed and presented on the cell surface, where they serve as targets for T-cell recognition. These complexes are critical for immunotherapeutic strategies, including peptide vaccines and T-cell receptor (TCR) based therapies. For example, the drug Tebentafusp is a bispecific T-cell engager that specifically recognizes the HLA-A*02:01/gp100:280-288 complex to treat uveal melanoma (Nathan et al., 2021, NEJM). The gp100:209-217 epitope, often modified to increase HLA affinity, has been used in clinical trials to stimulate anti-tumor immunity (Schwartzentruber et al., 2011, NEJM). Because gp100 is also expressed in normal melanocytes, targeting these epitopes can lead to on-target off-tumor toxicities such as vitiligo or uveitis. Overall, this peptide-MHC complex represents a validated target for redirecting the immune system against melanocytic tumors.

Other names

gp100:209-217gp100:280-288PMEL peptide-HLA complexHLA-A2/gp100Melanocyte protein PMEL epitopesgp100(209-217)gp100(280-288)

T-cell receptor (TCR) mediated recognition and redirection of T-cell cytotoxicity against cells presenting the gp100 peptide-HLA complex.