Melanoma antigen recognized by T cells 1 (27-35) peptide presented on HLA-A*0201 (MART-1(27-35)/HLA-A*0201)

The MART-1:27-35 peptide presented on HLA-A*0201 is a prominent peptide-major histocompatibility complex (pMHC) target in melanoma immunotherapy (Kawakami et al., 1994, PubMed: 7522230). MART-1, or Melan-A, is a differentiation antigen expressed specifically in melanocytes and melanoma cells (UniProt: Q16655). The AAGIGILTV peptide (residues 27-35) is the immunodominant epitope recognized by CD8+ T cells when bound to the HLA-A*0201 molecule, which is the most frequent MHC Class I allele in many populations (Johnson et al., 2009, PubMed: 19139330). Therapeutic interventions targeting this complex include TCR-engineered T-cell therapies and soluble TCR-based bispecifics like IMC-F10V. Clinical application of these therapies has demonstrated significant anti-tumor activity but is often associated with on-target, off-tumor toxicities due to MART-1 expression in normal melanocytes located in the skin, eyes, and inner ear (Chodon et al., 2014, PubMed: 24619560). Consequently, patients may experience vitiligo, uveitis, or hearing loss following treatment. Despite these safety concerns, the MART-1/HLA-A*0201 complex remains a critical benchmark for the development of high-affinity TCR-based medicines.

Other names

Melan-A (27-35)/HLA-A*0201MART-1:27-35/HLA-A2AAGIGILTV/HLA-A*02:01 complexMelanoma antigen recognized by T cells 1 (27-35)/HLA-A*0201

T-cell receptor (TCR) binding to the peptide-MHC complex, leading to T-cell activation and directed cytotoxicity against cells expressing the antigen.