Melanoma antigen recognized by T cells 1 peptide–Human leukocyte antigen-A*02:01 complex (MART-1/HLA-A*02:01)

The MART-1 peptide–HLA-A*02:01 complex is a specific peptide-major histocompatibility complex (pMHC) that plays a central role in the immune system's recognition of melanoma (PMID: 9430393). It is formed when the MART-1 protein (also known as MLANA, UniProt Q16655) is processed into short peptides, typically the immunodominant MART-1(26-35) or MART-1(27-35) fragments, and loaded onto the HLA-A*02:01 molecule for presentation on the cell surface (PMID: 16861295). This complex is highly expressed in the majority of melanomas and is also found in normal melanocytes, making it a differentiation antigen (PMID: 8162019). In the context of immunotherapy, this complex is targeted by engineered T-cell receptor (TCR) therapies and bispecific T-cell engagers designed to redirect the immune system to kill cells displaying the antigen (PMID: 16946036). Clinical trials have demonstrated that targeting this complex can lead to significant tumor shrinkage in metastatic melanoma patients (PMID: 19380867). However, because the target is also present in healthy melanocytes, safety concerns include autoimmune-like reactions such as vitiligo, uveitis, and hearing loss (PMID: 19380867).

Other names

MLANA peptide–HLA-A*02:01 complexMART-1(26-35)/HLA-A2Melan-A peptide–MHC complexMART-1/A2 complexMART-1(27-35)/HLA-A*02:01

The complex acts as a ligand for specific T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes, triggering T-cell activation and subsequent lysis of the target cell (PMID: 16946036).