Melanoma-associated antigen 4 peptide-HLA complex (MAGE-A4 peptide-HLA complex)

The Melanoma-associated antigen 4 peptide-HLA complex (commonly abbreviated as the MAGE-A4 peptide-HLA complex, or MAGE-A4 pMHC) refers to a molecular complex in which a peptide derived from the cancer-testis antigen MAGE-A4 is presented by a human leukocyte antigen (HLA) class I molecule, often HLA-A*02:01 (also known as HLA-A2)[1][4]. This complex is recognized by cytotoxic T lymphocytes through T cell receptors (TCRs), enabling the immune system to specifically target MAGE-A4–expressing tumor cells. MAGE-A4 is highly expressed in a significant proportion of tumors across several cancer types, while its expression is largely silent in normal adult tissues except testis, making it an immunotherapy target[2][3]. Therapies targeting this complex include pMHC-specific CAR-T cells and cancer vaccines designed to stimulate an anti-tumor immune response[2][3]. The underlying mechanism involves antigen presentation: the HLA class I molecule displays the MAGE-A4 peptide on the cell surface, which is recognized selectively by TCRs—enabling either natural cytotoxic T cells or engineered T-cell therapies to attack the tumor[1][3][4]. The structure and peptide conformation of this complex are critical for TCR recognition and specificity, and even minor sequence changes in the peptide or HLA can affect immune targeting and efficacy[1][4]. Key safety concerns include the risk of cross-reactivity and HLA restriction, limiting therapy to patients with compatible HLA alleles[3].

Other names

MAGE-A4 pMHC complexHLA-A2/MAGE-A4 complexHLA-A*02:01/MAGE-A4 complex

Induction of cytotoxic T lymphocyte response via presentation of MAGE-A4 peptide by HLA class I to specific TCR Activation of engineered T-cell therapies that recognize the MAGE-A4/HLA complex