MART-1-derived peptide–HLA-A*02:01 complex (MART-1/HLA-A2 complex)

The MART-1-derived peptide–HLA-A*02:01 complex is a specific molecular assembly consisting of a peptide fragment from the Melanoma Antigen Recognized by T cells 1 (MART-1), also known as Melan-A, presented by the Human Leukocyte Antigen (HLA) class I molecule A*02:01 (UniProt: Q16655). MART-1 is a melanocyte differentiation antigen that is highly and frequently expressed in most human melanomas, making it a prominent target for cancer immunotherapy (Kawakami et al., 1994, PNAS). The complex is recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, which triggers an immune response against the presenting cell (Slansky et al., 2000, Immunity). Therapeutic strategies targeting this complex include TCR-engineered T-cell therapies (TCR-T), such as BPX-701, and various TCR-like antibodies or bispecific molecules designed to mimic natural T-cell recognition. However, because MART-1 is also expressed in normal melanocytes in the skin, eye, and inner ear, clinical applications have been associated with on-target, off-tumor toxicities including vitiligo, uveitis, and hearing loss (Johnson et al., 2009, Blood).

Other names

Melan-A peptide-MHC complexMART-1(26-35)/HLA-A*02:01MART-1(27-35)/HLA-A*02:01Melan-A/HLA-A2 complexMART-1/MHC class I complex

T-cell receptor (TCR) binding and subsequent T-cell mediated cytotoxicity