Melanoma antigen recognized by T cells 1 (MART-1) peptide-HLA-A*0201 complex (MART-1/HLA-A*0201)

Melanoma antigen recognized by T cells 1 (MART-1), also known as Melan-A, is a lineage-specific protein primarily expressed in the melanosomes of normal melanocytes and the majority of melanoma cells (UniProt: Q16655). The MART-1 peptide-HLA-A*0201 complex is formed when the immunodominant MART-1 peptide (typically the 26-35 or 27-35 sequence) is processed and presented on the cell surface by the Human Leukocyte Antigen (HLA)-A*0201 molecule (PubMed: 8164633). This complex serves as a critical target for cancer immunotherapies, including TCR-engineered T cells and peptide vaccines, which aim to induce a cytotoxic T-lymphocyte response against melanoma (PubMed: 10426997). Because MART-1 is also expressed in healthy melanocytes, therapeutic targeting of this complex can lead to on-target, off-tumor toxicities such as vitiligo, uveitis, and hearing loss due to the destruction of melanocytes in the skin, eyes, and inner ear (PubMed: 19147751). Despite these challenges, it remains one of the most extensively studied targets in the development of cellular therapies for metastatic melanoma.

Other names

Melan-AMLANAMART1MART-1:26-35MART-1:27-35HLA-A2/MART-1 complex

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to cytotoxic T-lymphocyte (CTL) activation and tumor cell lysis.