Melanoma antigen recognized by T cells 1 (MART-1) peptide presented by Human Leukocyte Antigen A2 (HLA-A2) (Melan-A/MART-1:HLA-A2)

The Melan-A/MART-1 peptide presented by HLA-A2 is a major melanoma-associated antigen complex and a critical target in the field of cancer immunotherapy. It consists of an immunodominant peptide fragment (typically residues 26-35 or 27-35) derived from the Melan-A/MART-1 protein, which is a lineage-specific differentiation antigen expressed in normal melanocytes and over 80-95% of melanoma tumors (NIH, 2014; NIH, 2022). This peptide is presented on the cell surface by the Human Leukocyte Antigen A2 (HLA-A2), specifically the HLA-A*02:01 allele, where it can be recognized by the T-cell receptors (TCRs) of cytotoxic CD8+ T cells (NCI Drug Dictionary). Therapeutic strategies targeting this complex include adoptive cell transfer using TCR-engineered T cells (TCR-T) and various peptide-based vaccines designed to enhance the body's natural anti-tumor immunity. While these therapies have demonstrated the ability to induce significant tumor regression, they are frequently associated with 'on-target, off-tumor' toxicities because MART-1 is also expressed in healthy melanocytes located in the skin, eyes, and inner ear (Liv Hospital, 2026; NIH, 2022). Consequently, patients may experience side effects such as vitiligo, uveitis, and hearing impairment. Despite these challenges, the MART-1:HLA-A2 complex remains a foundational target for developing precision immunotherapies for metastatic and uveal melanoma.

Other names

MART-1:HLA-A2 complexMelan-A:HLA-A2 complexMART-1(26-35):HLA-A*02:01MART-1(27-35):HLA-A*02:01MLANA:HLA-A2Melanoma antigen recognized by T cells 1Antigen LB39-AAAntigen SK29-AAProtein Melan-A

Drugs targeting this complex typically utilize engineered T-cell receptors (TCR-T) or vaccines to induce a cytotoxic T-lymphocyte (CTL) response. TCR-T cells are modified to express a high-affinity receptor that specifically recognizes the MART-1 peptide within the HLA-A2 binding groove, leading to T-cell activation, cytokine release (e.g., IFN-gamma), and direct lysis of the target tumor cells (NIH, 2022; NCI Drug Dictionary).