HLADRB1

HLADRB1, also known as HLA-DRB1, is a gene that encodes the beta chain of the HLA-DR molecule, a class II major histocompatibility complex (MHC) protein expressed on antigen-presenting cells. The HLA-DR heterodimer consists of the HLA-DRA alpha chain paired with the HLA-DRB1 beta chain and presents peptide antigens to CD4+ T helper cells. The gene is located within the human MHC region on chromosome 6p21.31 and is one of the most polymorphic loci in the human genome, with hundreds of alleles that confer different peptide-binding properties.

HLA-DRB1 alleles determine the shape and chemistry of the peptide-binding groove, influencing which peptides can be presented and how T cells are selected. The gene is expressed broadly in professional antigen-presenting cells, including B cells, dendritic cells, and macrophages, and its expression is regulated during immune development. Peptide loading occurs in endosomal compartments with chaperones such as the invariant chain and HLA-DM, enabling diversified antigen presentation.

Genetic variation in HLA-DRB1 is strongly associated with immune-mediated diseases and with transplant compatibility. Certain DRB1 alleles and their haplotypes are linked to increased risk of rheumatoid arthritis (notably those with the shared epitope motif in the beta chain), type 1 diabetes, multiple sclerosis, and other autoimmune conditions. In transplantation, HLA-DRB1 matching between donor and recipient reduces the risk of graft-versus-host disease and improves outcomes.

Because of its profound polymorphism and role in immune recognition, HLA-DRB1 is a frequent focus of studies in immunology, infectious disease, autoimmunity, and personalized medicine.