Human leukocyte antigen A*02:01-presented melanoma antigen recognized by T cells 1 (MART-1) epitope (HLA-A2/MART-1)

The HLA-A*02:01-presented MART-1 epitope is a peptide-major histocompatibility complex (pMHC) that serves as a primary target for T-cell-based immunotherapies in melanoma [12, 14]. MART-1 (Melanoma Antigen Recognized by T cells 1), also known as Melan-A, is a melanocyte differentiation antigen that is highly expressed in over 80% of melanoma cases [3, 13]. The immunodominant epitope consists of a nonamer (AAGIGILTV) or decamer (EAAGIGILTV) peptide derived from the MART-1 protein, which is processed and presented on the cell surface by the HLA-A*02:01 allele [9, 21]. This complex is specifically recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, initiating a cascade that leads to the destruction of the target cell [15, 18]. Therapeutic interventions targeting this complex include TCR-engineered T-cell (TCR-T) therapies, such as those utilizing the DMF5 or 1D3 TCRs, as well as peptide-based vaccines and bispecific T-cell engagers [3, 4, 11]. A significant challenge in targeting this epitope is on-target, off-tumor toxicity, as MART-1 is also expressed in normal melanocytes found in the skin, eyes, and inner ear, potentially leading to vitiligo, uveitis, and hearing loss [4, 5, 13].

Other names

MART-1/HLA-A*02:01 complexMelan-A/HLA-A*02:01 complexMART-1(26-35) epitopeMART-1(27-35) epitopepMHC complex (MART-1/HLA-A2)

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex, leading to T-cell activation, redirection, and cytotoxic lysis of MART-1-expressing cells.