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

The HLA-A*02:01 presenting MART-1 epitope is a peptide-major histocompatibility complex (pMHC) that serves as a primary target for T-cell-based immunotherapies in melanoma (UniProt: Q16655; IMGT/HLA). MART-1, also known as Melan-A, is a protein specifically expressed in melanocytes and is highly prevalent in melanoma cells, making it a classic tumor-associated antigen (UniProt: Q16655). The HLA-A*02:01 allele is the most common MHC Class I molecule in Caucasian populations, providing a widely applicable scaffold for presenting the MART-1 peptide to the immune system (IMGT/HLA). Therapeutic agents, such as TCR-engineered T cells and bispecific T-cell engagers like ImmTACs (e.g., IMC-F10V), are engineered to recognize this specific pMHC complex with high affinity (PubMed: 19234140; Immunocore). When these drugs bind the target, they facilitate the directed lysis of melanoma cells by cytotoxic CD8+ T lymphocytes (PubMed: 19234140). Despite its efficacy in targeting tumors, MART-1 is also present in normal melanocytes found in the skin, eyes, and ears (UniProt: Q16655). Consequently, therapies targeting this complex often result in on-target, off-tumor toxicities, including vitiligo, uveitis, and hearing loss (PubMed: 19234140).

Other names

HLA-A*02:01/Melan-AHLA-A2/MART-1HLA-A*02:01/MLANAHLA-A*02:01/ELAGIGILTVMART-1/HLA-A2 complex

T-cell receptor (TCR) binding and T-cell redirection