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

The HLA-A*02:01-MART-1 peptide-MHC complex is a specific molecular assembly consisting of the Human Leukocyte Antigen (HLA) allele A*02:01 and a processed peptide fragment (typically the nonamer AAGIGILTV) derived from the MART-1 (Melan-A) protein [PMID: 8015814, 8127563]. This complex is presented on the cell surface of both malignant melanoma cells and normal melanocytes, where it serves as a ligand for specific T-cell receptors (TCRs) [PMID: 19386995]. As a lineage-specific differentiation antigen, MART-1 is expressed in the majority of cutaneous melanomas, making this pMHC complex a primary focus for immunotherapy development [PMID: 9290701]. Therapeutic strategies targeting this complex include TCR-engineered T-cell (TCR-T) therapies and bispecific T-cell engagers, which aim to induce a potent cytotoxic immune response against tumor cells [PMID: 24615736]. However, because the complex is also present on healthy melanocytes in the skin, eye, and inner ear, treatment can result in on-target, off-tumor toxicities such as vitiligo, uveitis, and hearing loss [PMID: 19386995]. Despite these challenges, the HLA-A*02:01-MART-1 complex remains a foundational model for understanding and developing antigen-specific cancer immunotherapies.

Other names

HLA-A*02:01-Melan-A complexMART-1/HLA-A2 complexMelan-A/HLA-A*02:01 complexA2/MART-1 pMHC

Redirection of cytotoxic T-lymphocytes to recognize and kill cells presenting the MART-1 peptide in the context of HLA-A*02:01 [PMID: 19386995].