HLA-DRB3 encodes a beta chain of HLA class II DR molecules that forms heterodimers with HLA-DRA to present peptide antigens to CD4+ T cells. The gene shows significant expression levels, with DRB3 mRNA approximately 2-3.5 fold lower than DRB1 in monocytes and B cells respectively 1. HLA-DRB3 molecules exhibit distinct peptide binding specificities that complement rather than overlap with DRB1 molecules, extending the repertoire of presentable antigens 12. The DRB3*0101 allele demonstrates unique binding patterns with particular structural features in its peptide binding site, while other alleles like DRB3*0202 show similarities to their haplotype-associated DRB1 molecules 2. HLA-DRB3 presents diverse pathogen-derived epitopes including dengue virus antigens, though with lower magnitude responses compared to DRB1 due to reduced cell surface expression 3. Clinically, specific DRB3 alleles are strongly associated with disease susceptibility - DRB3*01:01 is linked to HPA-1a alloimmunization in fetal/neonatal alloimmune thrombocytopenia 45, while DRB3*02:02 independently associates with PLA2R-related membranous nephropathy 6. These associations highlight HLA-DRB3's role in immune recognition and disease pathogenesis through antigen-specific T cell activation.