HLA-A*02:01–MAGE-C2 peptide complex (HLA-A2/MAGE-C2)

The HLA-A*02:01–MAGE-C2 peptide complex is a specific peptide-major histocompatibility complex (pMHC) found on the surface of various cancer cells. MAGE-C2 (Melanoma-associated antigen C2) is a member of the cancer-testis antigen family, which is typically expressed only in the male germline and certain tumors, making it a highly specific target for immunotherapy. In the context of HLA-A*02:01, specific immunogenic peptides such as LLFGLALIEV (residues 191-200) and ALKDVEERV (residues 336-344) are presented to the immune system. This complex is recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, which then initiate a targeted attack against the tumor. Therapeutic strategies targeting this complex include TCR-engineered T-cell (TCR-T) therapies and TCR-like antibodies, which are currently being evaluated in clinical trials for patients with melanoma and head and neck squamous cell carcinoma. Because MAGE-C2 expression is largely restricted to malignant tissues, therapies targeting this complex aim to minimize damage to healthy cells while providing a potent anti-tumor response.

Other names

MAGE-C2/HLA-A*02:01 complexHLA-A2-restricted MAGE-C2 antigenMAGE-C2 peptide-MHC complexMC2/A2 complex

TCR-engineered T cells (TCR-T) or TCR-like antibodies recognize the specific MAGE-C2 peptide presented by the HLA-A*02:01 molecule on the surface of tumor cells. Upon binding, the T cells are activated to release cytotoxic granules (perforin and granzymes) and cytokines (IFN-gamma), leading to the targeted lysis of the cancer cells.