HLA-A*02:01-restricted Melanoma-associated antigen recognized by T cells 1 (MART-1) peptide epitope (HLA-A*02:01/MART-1)

The HLA-A*02:01-presented MART-1 peptide epitope is a molecular complex consisting of a peptide fragment derived from the Melanoma-associated antigen recognized by T cells 1 (MART-1/Melan-A) bound to the Human Leukocyte Antigen (HLA) A*02:01 molecule. MART-1 is a melanocyte differentiation antigen that is highly and frequently expressed in malignant melanoma, but its expression in normal tissues is restricted to melanocytes in the skin, eye, and inner ear (UniProt: Q16655). This peptide-MHC complex serves as a critical target for the immune system, specifically for CD8+ cytotoxic T lymphocytes which recognize the epitope via their T-cell receptors (TCRs) (PubMed: 8146140). Therapeutic interventions targeting this epitope include TCR-engineered T-cell therapies, peptide vaccines, and soluble TCR-based bispecifics designed to redirect T-cell cytotoxicity against melanoma cells (PubMed: 19139349). While effective in inducing tumor regression, targeting this epitope often results in on-target off-tumor toxicities, such as vitiligo, uveitis, and hearing loss, due to the destruction of healthy melanocytes (PubMed: 21300927). Consequently, it remains a benchmark target for developing and testing high-affinity TCR therapies in the context of solid tumors.

Other names

Melan-A peptideMART-1(26-35) epitopeMART-1(27-35) epitopeHLA-A2/MART-1 complexMLANA peptide

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex on the surface of tumor cells, leading to cytotoxic T-lymphocyte activation and subsequent lysis of the target cell (PubMed: 8146140).