Human leukocyte antigen DPB1*04:01–peptide complex (HLA-DPB1*04:01)

The Human leukocyte antigen DPB1*04:01 (HLA-DPB1*04:01)–peptide complex is a major histocompatibility complex (MHC) class II molecule that plays a pivotal role in the adaptive immune system by presenting exogenous peptides to CD4+ T cells [PMID: 25607530]. As one of the most prevalent HLA-DP alleles in Western populations, it serves as a critical restriction element for the recognition of both pathogen-derived antigens and tumor-associated antigens [PMID: 26034044]. In clinical oncology, this complex is a primary target for TCR-engineered T-cell therapies, where synthetic T-cell receptors are designed to recognize specific peptides, such as those from MAGE-A3 or NY-ESO-1, when presented by HLA-DPB1*04:01 [PMID: 23913173]. Beyond its role in cancer immunotherapy, the complex is a well-known genetic risk factor for Chronic Beryllium Disease (CBD), a granulomatous lung disorder caused by the immune system's reaction to beryllium-modified peptides presented by this specific HLA molecule [PMID: 12815044]. Therapeutic interventions targeting this complex aim to either stimulate a robust immune response against malignant cells or suppress aberrant immune activation in hypersensitivity and autoimmune conditions. The structural specificity of the HLA-DPB1*04:01 binding pocket is a key consideration in the development of these therapies to ensure high affinity and minimize off-target cross-reactivity [PMID: 25108025].

Other names

HLA-DP4HLA-DPB1*0401DPB1*04:01MHC class II antigen DPB1*04:01

The complex functions as a ligand for T-cell receptors (TCRs). Engineered TCR-T cells or endogenous T cells bind to the specific peptide-MHC complex, triggering a signaling cascade that leads to T-cell activation, cytokine production, and the targeted destruction of cells presenting the antigen.