HLA-DPA1 is a major histocompatibility complex class II alpha chain that forms heterodimers with HLA-DPB1 to present exogenous peptide antigens to CD4+ T cells 1. The protein binds peptides of 10-30 residues derived from endocytosed antigens and displays them on antigen-presenting cell surfaces, initiating adaptive immune responses through T cell activation and proliferation. Mechanistically, HLA-DPA1 associates with HLA-DPB1 and CD74 in the endoplasmic reticulum, then translocates to endosomal/lysosomal compartments where antigenic peptides are loaded following CD74 degradation and CLIP removal 1. The molecule stabilizes until high-affinity peptides bind, then transports to the cell membrane for T cell recognition. Genetic studies reveal HLA-DPA1 polymorphisms associate with multiple diseases. A variant (rs2856830) in the HLA-DPA1/DPB1 locus is associated with pulmonary arterial hypertension (PAH) susceptibility and survival outcomes, with C/C homozygotes showing doubled median survival (13.5 years) compared to T/T homozygotes (7.0 years) 2. Separately, rs13203715 causally associates with PAH through HLA-DPA1 downregulation in non-classical monocytes, promoting immune dysregulation and vascular remodeling 1. In ulcerative colitis, HLA-DPA1∗01:03-DPB1∗04:01 is a disease risk haplotype that engages NKp44 on epithelial cells, activating NK-mediated intestinal damage 3. Clinically, HLA-DPA1 overexpression in lung adenocarcinoma correlates with increased immune infiltration, reduced proliferation, and improved cisplatin sensitivity 4, suggesting therapeutic potential as a prognostic biomarker. Conversely, AML relapse after allogeneic transplantation features MHC class II downregulation including HLA-DPA1 (3-12 fold reduction), representing immune escape 5.