HLA-A*02:01-presented MART-1 (27-35) peptide complex (HLA-A2/MART-1(27-35))

The HLA-A*02:01-presented MART-1 (27-35) peptide complex is a specific antigen-MHC assembly that plays a pivotal role in the immune system's ability to recognize melanoma cells (Kawakami et al., 1994). MART-1 (Melanoma 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 specific peptide fragment spanning residues 27-35 (AAGIGILTV) is processed intracellularly and loaded onto the HLA-A*02:01 molecule for presentation on the cell surface. This complex is specifically recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, making it a primary target for various immunotherapeutic strategies, including TCR-engineered T-cell (TCR-T) therapies and cancer vaccines (Johnson et al., 2009). While highly effective at inducing tumor regression in clinical trials, therapeutic targeting of this complex can lead to "on-target, off-tumor" toxicities because MART-1 is also expressed in healthy melanocytes located in the skin, eyes, and inner ear. These toxicities can manifest as vitiligo, uveitis, or hearing loss, presenting a significant therapeutic challenge (Johnson et al., 2009). Despite these concerns, the high specificity and prevalence of the MART-1/HLA-A2 complex continue to make it a cornerstone of adoptive cell therapy research in oncology.

Other names

Melan-A (27-35)/HLA-A*02:01MART-1/A2 complexAAGIGILTV-HLA-A*02:01 complexMART-1(27-35)-HLA-A*02:01HLA-A*02:01-MART-1(27-35)

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex triggers cytotoxic T-lymphocyte activation and tumor cell lysis.