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

MART-1 (Melanoma-associated antigen recognized by T cells 1), also known as Melan-A, is a lineage-specific differentiation antigen primarily expressed in melanocytes and the majority of malignant melanomas (Kawakami et al., 1994, PNAS). The MART-1 peptide-HLA-A*02:01 complex is a major target for cancer immunotherapy, consisting of an immunodominant peptide (such as MART-1 26-35) presented by the Human Leukocyte Antigen (HLA) class I molecule A*02:01 (Coulie et al., 1994, J. Exp. Med.). This complex is recognized by the T-cell receptors (TCRs) of cytotoxic T lymphocytes, making it a focal point for TCR-engineered T-cell therapies and peptide-based vaccines (Johnson et al., 2009, Blood). In clinical settings, targeting this complex has demonstrated the ability to induce significant tumor regression in patients with metastatic melanoma. However, because MART-1 is also expressed in normal melanocytes in the skin, eye, and inner ear, a significant safety concern is on-target, off-tumor toxicity. This toxicity can manifest as vitiligo, uveitis, or hearing loss, necessitating careful management of T-cell potency and specificity (Morgan et al., 2006, Science). Current research aims to optimize TCR affinity and develop next-generation therapies that can distinguish between high-density antigen presentation on tumor cells and lower-density presentation on healthy tissues. The complex remains a benchmark for validating new T-cell therapy platforms due to its well-characterized immunology and high prevalence in the patient population.

Other names

Melan-A peptide-HLA-A*02:01 complexMART-1(26-35)/HLA-A2MART-1(27-35)/HLA-A2AAGIGILTV/HLA-A*02:01ELAGIGILTV/HLA-A*02:01

T-cell receptor-mediated recognition of peptide-MHC complex leading to cytotoxic T-lymphocyte activation and tumor cell lysis