Melanoma-associated antigen 3 peptide presented by HLA-DPB1*0401 (MAGE-A3/HLA-DPB1*0401)

The MAGE-A3 peptide presented by HLA-DPB1*0401 is a specific peptide-major histocompatibility complex (pMHC) target used in the development of precision immunotherapies. Melanoma-associated antigen 3 (MAGE-A3) is a cancer-testis antigen (CTA) that is typically not expressed in normal adult tissues except for the testis, but is frequently upregulated in solid tumors such as melanoma and non-small cell lung cancer, making it an ideal tumor-specific antigen (UniProt P43357). The presentation of the MAGE-A3:243-258 peptide by the HLA-DPB1*0401 allele allows for the recruitment of CD4+ helper T cells, which play a crucial role in orchestrating a sustained anti-tumor immune response (PMID: 15154915). This specific pMHC complex has been the focus of clinical trials using TCR-engineered T cells, which are modified to express a high-affinity TCR specific for this epitope (PMID: 26169254). Because HLA-DPB1*0401 is highly prevalent in many populations, particularly Caucasians, this target offers a broader patient reach compared to rarer HLA restrictions. However, therapeutic development is complicated by the high sequence homology between MAGE-A3 and other MAGE family proteins, necessitating rigorous screening for cross-reactivity to avoid off-target adverse effects (PMID: 23558891).

Other names

MAGE-A3:243-258/HLA-DP4MAGE-A3/DP4 complexMAGE-A3/HLA-DPB1*04:01Melanoma-associated antigen 3/HLA-DPB1*04:01

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to T-cell activation, cytokine production, and tumor cell lysis.