HLA-A*02:01-presented Melanocyte protein PMEL (gp100) peptide epitope (HLA-A*02:01/gp100)

The HLA-A*02:01-presented gp100 peptide epitope is a molecular complex consisting of the human leukocyte antigen (HLA) allele A*02:01 and a specific peptide fragment derived from the Melanocyte Protein PMEL, also known as gp100 (Source: UniProt P40967). gp100 is a transmembrane glycoprotein primarily expressed in melanocytes and is highly prevalent in melanoma cells, making it a significant target for immunotherapy (Source: PubMed: 10359807). This specific peptide-MHC complex is recognized by the T-cell receptor (TCR), facilitating the identification and destruction of tumor cells by cytotoxic T lymphocytes. Therapeutic interventions targeting this complex include the bispecific TCR-anti-CD3 fusion protein Tebentafusp, which redirects T cells to kill gp100-expressing melanoma cells (Source: FDA Label for Kimmtrak). Additionally, synthetic peptide vaccines like gp100:209-217(210M) are used to prime and expand the patient's own T-cell population against this epitope (Source: PubMed: 15150594). Because gp100 is also present in healthy melanocytes, common safety concerns include autoimmune-related skin toxicities such as vitiligo and systemic issues like cytokine release syndrome. Clinical efficacy is strictly dependent on the patient's HLA genotype, requiring HLA-A*02:01 positivity for treatment eligibility.

Other names

gp100 peptidePMEL peptideHLA-A*02:01/gp100(209-217)gp100:209-217Melanocyte protein PMELSilver locus protein homologg209-2M

The target is a specific peptide-MHC complex recognized by T-cell receptors (TCRs). Therapeutic agents either act as vaccines to stimulate endogenous T-cell expansion against this epitope or as bispecific molecules (ImmTACs) that bridge the peptide-MHC complex on tumor cells with CD3 on T-cells, leading to direct tumor cell lysis.