HLA-DPB1 is a major histocompatibility complex class II beta chain that functions as an antigen-presenting molecule expressed on antigen-presenting cells. It forms heterodimeric complexes with HLA-DPA1 alpha chains to present exogenously derived peptides (10-30 residues) to CD4+ T cells, enabling adaptive immune recognition of pathogens and antigens accessed through endocytic pathways. The peptide-binding process involves coordinated action with CD74, HLA-DM, and lysosomal proteases to load antigenic peptides onto the HLA-DP complex at the cell surface. HLA-DPB1 polymorphisms significantly influence disease susceptibility across multiple conditions. Specific alleles (*0401, *0601) increase rheumatoid arthritis risk, while *0101, *0402, and *0501 are protective 1. The HLA-DPB1(Glu69) residue is implicated in chr6 beryllium disease susceptibility in occupationally exposed workers 2. HLA-DPB1*03:01 increases cervical cancer risk, whereas *04:02 is protective 3. HLA-DPB1*13:01 provides protection against severe COVID-19 4. Specific alleles (*04, *18) confer protection against leprosy, while *105 increases susceptibility 5. Additionally, HLA-DPB1 variants influence skin microbiome composition and malodor production 6. These polymorphisms affect T cell epitope diversity and expression levels, making HLA-DPB1 genetic variation critical for transplantation donor selection 7.