HLA class II histocompatibility antigen, DRB1*15:01 beta chain (HLA-DRB1*15:01)

The HLA class II histocompatibility antigen, DRB1*15:01 beta chain is a specific allelic variant of the HLA-DRB1 beta chain protein, which forms a heterodimer with the invariant HLA-DRA alpha chain to create an MHC class II molecule expressed on professional antigen-presenting cells like dendritic cells, macrophages, and B cells. This complex presents extracellular peptides (typically 10-30 amino acids long) derived from endocytosed antigens, displaying them on the cell surface for recognition by CD4-positive T helper cells via their T cell receptors, thereby initiating adaptive immune responses including antibody production and macrophage activation to combat infections or transformed cells. In the HLA-DR15 haplotype, DRB1*15:01 (also called DR2b) pairs with DRB5*01:01 (DR2a), presenting complementary peptide repertoires with distinct anchor motifs (e.g., bulky hydrophobics at P1 for DR2b), contributing roughly equally to the overall peptidome despite low overlap in ligands. The allele is strongly associated with autoimmune diseases like multiple sclerosis, where it may present self-peptides or molecular mimics from pathogens, driving pathogenic T cell responses, and rheumatoid arthritis risk via polymorphisms at key residues. In tumors, it presents neoantigens from apoptotic cells or autophagy-derived peptides, supporting anti-tumor immunity, though no approved drugs directly target it; research explores peptide vaccines and CAR-T therapies leveraging its specificity. Challenges include its role in central tolerance via thymic selection and potential for immunotherapy-induced autoimmunity.

Other names

HLA-DRB1DRB1*15:01DR2b (within HLA-DR15 haplotype)

None identified (no direct small-molecule drugs; targeted indirectly via peptide vaccines or immunotherapies in research contexts)