Solute carrier family 45 member 2-derived peptide–HLA-A*02:01 or HLA-A*24:02 complex (SLC45A2-HLA complex)

The SLC45A2-derived peptide–HLA complex is a highly specific tumor-associated antigen target primarily found on the surface of melanoma cells. SLC45A2 (also known as Membrane-Associated Transporter Protein or MATP) is a protein involved in melanin synthesis and is overexpressed in the majority of melanoma cases, including uveal melanoma. Intracellular SLC45A2 is processed by the proteasome into short peptides, such as the immunodominant SLC45A2_284-292 fragment, which are then transported to the cell surface and presented by Human Leukocyte Antigen (HLA) alleles, specifically HLA-A*02:01 or HLA-A*24:02. This peptide-MHC complex serves as a critical recognition site for the immune system, particularly for cytotoxic T lymphocytes. Because SLC45A2 expression is largely restricted to the melanocytic lineage, this complex is an attractive target for TCR-engineered T-cell therapies and TCR-like bispecific molecules. However, therapeutic development must account for potential 'on-target, off-tumor' effects in normal pigmented tissues such as the skin and the retinal pigment epithelium of the eye.

Other names

SLC45A2-MHC class I complexMATP-derived peptide-HLA complexSLC45A2-HLA-A2 complexSLC45A2-HLA-A24 complexMelanoma-associated antigen SLC45A2 peptide-HLA complex

Therapeutic agents such as TCR-engineered T cells (TCR-T) or TCR-like antibodies recognize the specific SLC45A2 peptide fragment presented within the groove of the HLA-A*02:01 or HLA-A*24:02 molecule, triggering T-cell mediated lysis of the tumor cell.