HLA-A*02:01-gp100 peptide complex (HLA-A2/gp100)

The HLA-A*02:01-gp100 peptide complex is a specific peptide-major histocompatibility complex (pMHC) found on the surface of melanocytes and melanoma cells. It consists of the HLA-A*02:01 molecule presenting an 8-10 amino acid fragment derived from the gp100 protein (also known as PMEL), a lineage-specific antigen involved in melanosome biogenesis. This complex serves as a critical target for cancer immunotherapy because gp100 is highly overexpressed in melanoma, including uveal and cutaneous subtypes, while its normal expression is restricted to melanocytes. Therapeutic strategies targeting this complex include T-cell receptor (TCR) engineered T-cells and bispecific TCR-anti-CD3 fusion proteins like Tebentafusp. Tebentafusp, the first-in-class ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer), binds with high affinity to the HLA-A*02:01-gp100 complex and recruits T-cells to the tumor site via a CD3 effector domain. This interaction triggers the release of inflammatory cytokines and cytolytic proteins, leading to the targeted destruction of melanoma cells. Clinical application is restricted to patients who are HLA-A*02:01 positive, making the HLA genotype a mandatory companion diagnostic for treatment.

Other names

HLA-A*02:01-PMEL complexMHC-gp100 peptide complexHLA-A2-gp100(209-217)HLA-A2-gp100(154-162)pMHC complex (gp100)

T-cell redirection via bispecific TCR-anti-CD3 fusion proteins or direct recognition by engineered T-cell receptors (TCR-T) to induce cytotoxic killing of cells presenting the gp100 peptide.