Melanoma-associated antigen 3 peptide presented by Human Leukocyte Antigen DPB1*04:01 (MAGE-A3/HLA-DPB1*04:01)

Melanoma-associated antigen 3 (MAGE-A3) is a prominent member of the cancer-testis antigen family, characterized by high expression in various malignancies—such as melanoma and non-small cell lung cancer—while remaining transcriptionally silent in normal adult tissues, with the exception of immune-privileged sites like the testis and placenta (UniProt P43357) [1]. The specific complex formed by the MAGE-A3-derived peptide (residues 243-258: KKLLTQHFVQENYLEY) presented by the MHC Class II molecule HLA-DPB1*04:01 (also known as HLA-DP4) is a critical target for CD4+ T-cell-mediated anti-tumor immunity (PubMed: 11015450) [2]. HLA-DPB1*04:01 is one of the most frequent HLA alleles in human populations, particularly among Caucasians, making this peptide-MHC complex a broadly applicable target for immunotherapy (IMGT/HLA) [3]. Therapeutic approaches targeting this complex primarily involve T-cell receptor (TCR) engineered T-cell therapies, which aim to redirect the patient's immune system to recognize and destroy cancer cells expressing MAGE-A3 (PubMed: 25583380) [4]. While clinical trials have shown promise in inducing tumor regression, significant challenges include managing potential off-target toxicities and ensuring the specificity of the engineered TCRs to avoid cross-reactivity with other MAGE family members or healthy tissues (PubMed: 23733339) [5].

Other names

MAGE-A3:243-258/HLA-DP4MAGE-A3/HLA-DP4 complexMAGE-A3/DPB1*04:01MAGE-A3 peptide-MHC Class II complex

Recognition of the specific peptide-MHC complex by engineered T-cell receptors (TCRs) on the surface of T cells, leading to T-cell activation, secretion of pro-inflammatory cytokines, and direct cytotoxic lysis of MAGE-A3-expressing tumor cells.