Melanoma antigen recognized by T cells 1 peptide–Major Histocompatibility Complex (MART-1 peptide–MHC complex) (MART-1–MHC)

The MART-1 peptide–MHC complex is a critical immunological target in the treatment of melanoma. MART-1 (Melanoma Antigen Recognized by T cells 1), also known as Melan-A, is a protein specifically expressed in melanocytes and the majority of melanoma tumors (UniProt Q16655). When processed, MART-1 peptides (most notably the MART-1 26-35 or 27-35 epitopes) are presented on the cell surface by Major Histocompatibility Complex (MHC) Class I molecules, particularly HLA-A*02:01. This complex is recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, making it a primary focus for cancer immunotherapy (PubMed: 16946036). Therapeutic strategies targeting this complex include peptide vaccines designed to be presented by dendritic cells, TCR-engineered T-cell therapies (TCR-T), and bispecific TCR molecules (ImmTACs) that redirect T cells to kill melanoma cells (Immuncore). However, because MART-1 is also present in healthy melanocytes, treatments can cause off-tumor toxicities such as vitiligo, uveitis, and ototoxicity (PubMed: 19244442). The complex serves as a bridge between the innate and adaptive immune systems when presented on dendritic cells, facilitating the priming of naive T cells.

Other names

Melan-A peptide–HLA complexMART-1/HLA-A*02:01 complexMelan-A/MHC complexMART-1(26-35)/HLA-A2

Binding of therapeutic T-cell receptors (TCRs) or TCR-mimetic antibodies to the peptide-MHC complex, leading to T-cell mediated lysis of target cells or priming of naive T cells when presented by dendritic cells.