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

The Human leukocyte antigen A*02:01 - Melanoma antigen recognized by T cells 1 complex is a peptide-major histocompatibility complex (pMHC) that serves as a critical target in melanoma immunotherapy (NIH, 1.2.1). It consists of the HLA-A*02:01 class I molecule presenting an immunodominant peptide derived from the MART-1 (Melan-A) protein, a differentiation antigen found in melanocytes and most melanoma cells (PubMed, 1.2.2). This complex is recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, which triggers an immune response against the tumor (NIH, 1.4.1). Therapeutic approaches targeting this epitope include TCR-engineered T-cell therapies and peptide-based vaccines, which aim to harness the immune system to eliminate melanoma cells (ClinicalTrials.gov, 1.1.4). Despite its high expression in tumors, MART-1 is also present in normal melanocytes in the skin, eyes, and inner ear, leading to potential on-target off-tumor toxicities such as vitiligo, uveitis, and hearing loss (NIH, 1.3.1). Clinical trials have shown that high-affinity TCRs can induce significant tumor regression but must be carefully managed to mitigate these adverse effects (NIH, 1.3.2). The complex remains a foundational model for understanding T-cell recognition and developing precision immunotherapies for solid tumors (NIH, 1.4.1).

Other names

MART-1/HLA-A*02:01Melan-A/HLA-A*02:01MART-1(26-35)/HLA-A*02:01MART-1(27-35)/HLA-A*02:01AAGIGILTV/HLA-A*02:01ELAGIGILTV/HLA-A*02:01HLA-A2/MART-1HLA-A*0201/MART-1

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex on the surface of target cells, leading to the activation of cytotoxic T lymphocytes and the subsequent release of perforins and granzymes to induce apoptosis in the antigen-presenting tumor cells.