Melanoma-associated antigen recognized by T cells 1 (MART-1) peptide-HLA class I complex (MART-1/HLA complex)

MART-1 (Melanoma-associated antigen recognized by T cells 1), also known as Melan-A, is a lineage-specific differentiation antigen primarily expressed in melanocytes and melanoma cells (UniProt Q16655). The therapeutic target is the MART-1 peptide fragment (typically the immunodominant MART-1 26-35 or 27-35 sequences) presented on the cell surface by Human Leukocyte Antigen (HLA) class I molecules, most frequently HLA-A*02:01 (Kawakami et al., 1994). This peptide-MHC complex is recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, making it a significant target for cancer immunotherapies including TCR-engineered T-cell therapies (TCR-T), soluble TCR-based bispecifics (ImmTACs), and peptide-based vaccines. In melanoma, MART-1 is highly and frequently expressed, providing a specific marker for the immune system to identify malignant cells. However, because MART-1 is also present in normal melanocytes, therapies targeting this complex often result in on-target, off-tumor toxicities such as vitiligo (skin depigmentation), uveitis (eye inflammation), and ototoxicity (hearing loss) (Johnson et al., 2009). Clinical management of these toxicities is a critical component of MART-1 targeted therapeutic strategies.

Other names

Melan-AMLANAMART1MART-1(26-35) peptideMART-1(27-35) peptideHLA-A*02:01/MART-1 complex

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex, leading to T-cell activation, cytokine secretion, and cytotoxic lysis of the target cell.