Melanoma-associated antigen 1 peptide–Major histocompatibility complex class I complex (MAGE-A1–MHC I)

MAGE-A1 peptide–MHC class I complexes are specialized cell-surface structures consisting of a peptide derived from the Melanoma-associated antigen 1 (MAGE-A1) protein presented by Major Histocompatibility Complex (MHC) class I molecules, most commonly HLA-A1 (UniProt: P43355). MAGE-A1 is a member of the cancer-testis antigen family, which is typically expressed only in male germ cells (where MHC is absent) and various malignancies, making these complexes highly specific targets for immunotherapy (PubMed: 1840444). In melanoma and other cancers, the intracellular MAGE-A1 protein is degraded by the proteasome, and the resulting peptides are transported into the endoplasmic reticulum to be loaded onto MHC class I molecules for surface display. These complexes are recognized by the T-cell receptors (TCRs) of cytotoxic T lymphocytes, triggering an immune response against the tumor cell (PubMed: 7904373). Therapeutic strategies targeting these complexes include TCR-engineered T-cell (TCR-T) therapies, TCR-like antibodies, and peptide vaccines designed to enhance the body's ability to eliminate MAGE-A1-positive cancer cells while sparing healthy tissues (PubMed: 31515463).

Other names

MAGE-A1–HLA-A1 complexMAGE-A1–HLA-A*01:01 complexMAGE1–MHC complexMelanoma antigen family A 1 peptide–MHC complexMAGE-A1–HLA complex

Recognition of the specific MAGE-A1 peptide (e.g., EADPTGHSY) presented by HLA-A1 molecules by engineered T-cell receptors (TCRs) or TCR-like antibodies, leading to the activation of cytotoxic T-lymphocytes and subsequent lysis of the tumor cell (PubMed: 7904373).