Melanoma antigen recognized by T cells 1 peptide–HLA-A*02:01 complex (MART-1/HLA-A2)

The MART-1 peptide–MHC class I complex is a prominent therapeutic target in oncology, specifically for the treatment of metastatic melanoma. It consists of an immunodominant peptide derived from the Melan-A (MART-1) protein, typically the 26-35 or 27-35 amino acid sequence, presented on the cell surface by the Major Histocompatibility Complex (MHC) class I molecule HLA-A*02:01 (Kawakami et al., 1994, PubMed: 8145820). MART-1 is a melanocyte differentiation antigen that is highly expressed in most melanoma tumors but has restricted expression in normal tissues, primarily limited to melanocytes in the skin, retina, and inner ear (UniProt: Q16655). This complex is specifically recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, making it a primary candidate for TCR-engineered T-cell (TCR-T) therapies and bispecific T-cell engagers (Morgan et al., 2006, PubMed: 16946075). Clinical trials targeting this complex have demonstrated the ability to induce significant tumor regression in patients with advanced melanoma. However, because the target is also present on normal melanocytes, therapeutic intervention can lead to on-target, off-tumor toxicities, including vitiligo, uveitis, and hearing loss (Johnson et al., 2009, PubMed: 19147751).

Other names

Melan-A peptide-MHC complexMART-1:HLA-A*02:01MART-1(26-35)/HLA-A2MLANA/HLA-A2 complexMART-1 peptide-MHC class I complex

T-cell receptor (TCR) binding to the peptide-MHC complex, triggering T-cell activation and cytotoxic destruction of the target cell.