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

The HLA-A*02:01-presented MART-1 (27-35) epitope is a prominent tumor-associated antigen complex consisting of a peptide fragment from the Melan-A protein bound to the Human Leukocyte Antigen (HLA) A*02:01 molecule. MART-1 is a lineage-specific differentiation antigen primarily expressed in melanocytes and melanoma cells, making its HLA-presented epitopes ideal targets for cancer immunotherapy (Kawakami et al., 1994). The specific nonamer sequence AAGIGILTV (or its optimized analogue ELAGIGILTV) is recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, triggering an immune response against the presenting cell (Cole et al., 2007). This complex is a major target for various therapeutic modalities, including TCR-engineered T-cell (TCR-T) therapies, bispecific TCR molecules, and cancer vaccines. Clinical applications focus on treating metastatic melanoma, where MART-1 expression is high. However, because MART-1 is also present in healthy melanocytes, therapeutic targeting can result in on-target, off-tumor toxicities such as vitiligo, uveitis, and hearing loss (Johnson et al., 2009). Despite these risks, the HLA-A2/MART-1 complex remains a foundational model in the field of T-cell immunology and immunotherapy development.

Other names

Melan-A (27-35) epitopeMART-1 (27-35) peptideAAGIGILTV peptideHLA-A*02:01/Melan-A complexMART1-A2

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to T-cell activation and targeted lysis of MART-1 expressing cells.