Melanoma-associated antigen recognized by T cells 1 peptide presented by Human Leukocyte Antigen A*02:01 (MART-1/HLA-A*02:01)

MART-1 (Melanoma-associated antigen recognized by T cells 1), also known as Melan-A, is a melanocyte differentiation antigen that is highly expressed in most melanomas (UniProt: Q16655). The specific target "MART-1 peptide presented by HLA-A*02:01" refers to the immunodominant peptide fragment (often MART-1 26-35) bound to the Human Leukocyte Antigen A*02:01 molecule on the cell surface (PubMed: 8175769). This peptide-MHC (pMHC) complex is recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, making it a primary target for cancer immunotherapies such as TCR-engineered T-cell (TCR-T) therapy and peptide vaccines (PubMed: 15150594). While MART-1 is a potent target for inducing anti-tumor immunity, its expression in normal melanocytes located in the skin, eye, and inner ear presents significant therapeutic challenges. Clinical trials have demonstrated that targeting this complex can lead to "on-target, off-tumor" toxicities, including vitiligo, uveitis, and hearing loss, due to the destruction of healthy melanocytes (PubMed: 19244159). Consequently, patient selection requires screening for both the HLA-A*02:01 genotype and MART-1 expression in tumor tissue. Therapeutic strategies aim to exploit the high expression of MART-1 in melanoma to direct immune-mediated destruction of tumor cells. Despite the risk of autoimmunity, MART-1 remains a foundational target in the development of adoptive cell therapies for metastatic melanoma.

Other names

Melan-A/HLA-A*02:01MART-1(26-35)/HLA-A2MLANA/HLA-A*02:01MART-1/HLA-A2

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to cytotoxic T-lymphocyte activation and lysis of tumor cells (PubMed: 19244159).