HLA-A*02:01-bound MART-1 peptide complex (HLA-A2/MART-1)

The HLA-A*02:01-bound MART-1 peptide complex is a specific peptide-major histocompatibility complex (pMHC) that serves as a critical target for melanoma immunotherapy (Kawakami et al., 1994, PMID: 8124719). MART-1 (Melanoma-associated Antigen Recognized by T cells 1), also known as Melan-A, is a protein primarily expressed in melanocytes and is highly prevalent in melanoma tumors (UniProt Q16655). The complex is formed when the MART-1(26-35) or MART-1(27-35) peptide is processed and presented on the cell surface by the HLA-A*02:01 molecule, the most common MHC Class I allele in many populations (Sliz et al., 2001, PMID: 11435473). This pMHC complex is recognized by specific T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes, triggering an immune response against the presenting cell. Therapeutic interventions targeting this complex include TCR-engineered T-cell therapies (e.g., KITE-753) and peptide vaccines designed to expand MART-1-specific T-cell populations (Johnson et al., 2009, PMID: 19386995). A significant challenge in targeting this complex is on-target, off-tumor toxicity, as MART-1 is also expressed in healthy melanocytes in the skin, eyes, and inner ear, potentially leading to vitiligo, uveitis, and hearing loss.

Other names

HLA-A*02:01/Melan-A complexMART-1(26-35) epitopeMART-1(27-35) epitopeMelan-A/HLA-A2 complexMART-1/HLA-A*02:01

Targeting of the peptide-MHC complex by engineered T-cell receptors (TCRs) or TCR-like antibodies to induce cytotoxic T-lymphocyte mediated lysis of tumor cells.