Human leukocyte antigen A*02:01 presenting Premelanosome protein (gp100) peptide (HLA-A*02:01/gp100)

The HLA-A*02:01 presenting PMEL/gp100 peptide is a specific peptide-major histocompatibility complex (pMHC) found on the surface of melanocytes and melanoma cells. PMEL, also known as gp100, is a transmembrane glycoprotein essential for melanosome maturation, and its processed peptides are presented by the HLA-A*02:01 allele to the immune system (UniProt P40967). This complex is a validated therapeutic target in melanoma, particularly uveal melanoma, where it is recognized by engineered T-cell receptors and bispecific molecules (PMID: 34554117). The most prominent drug targeting this complex is Tebentafusp, an ImmTAC (Immune mobilizing monoclonal TCR Against Cancer) that redirects T cells to kill cells presenting the gp100 peptide YLEPGPVTA (FDA Label: Kimmtrak). Because gp100 is a lineage-specific antigen, its expression is largely restricted to melanocytic cells, providing a window for therapeutic targeting. However, since normal melanocytes also present this complex, treatment can lead to on-target off-tumor toxicities such as vitiligo and ocular inflammation. Patient selection for these therapies requires screening for the HLA-A*02:01 genotype and confirmation of gp100 expression.

Other names

HLA-A*02:01/PMELHLA-A2/gp100gp100:280-288/HLA-A*02:01gp100:209-217/HLA-A*02:01Melanocyte-specific gp100/HLA-A2 complex

T-cell redirection via bispecific fusion proteins or T-cell receptor-engineered T-cells (TCR-T) to induce cytotoxic lysis of cells presenting the specific peptide-MHC complex.