DRB3

DRB3, also known as HLA-DRB3, is a human gene that encodes the beta chain of the MHC class II molecule DR. It is located in the HLA class II region on chromosome 6p21.3, a locus rich in immune-related genes. The HLA-DR molecule functions as an antigen-presenting receptor on the surface of professional antigen-presenting cells, where it presents extracellular peptide fragments to CD4+ T cells.

In the class II molecule, the alpha and beta chains form a heterodimer; the alpha chain is encoded by HLA-DRA and the beta chain by HLA-DRB3 in individuals carrying that gene. DRB3 is one of several DRB genes in the HLA region; its presence and expression are tied to specific haplotypes. Not all individuals carry DRB3, and its expression is commonly linked to certain DRB1 haplotypes, such as those carrying DRB3 as a complementary beta chain.

The DRB3 gene is highly polymorphic, with many alleles contributing to substantial variation in the peptide-binding groove of the DR molecule. This diversity expands the repertoire of peptides that can be presented to CD4+ T cells, influencing immune recognition and response. DRB3 expression is generally restricted to cells that partake in antigen presentation, including B cells, dendritic cells, and macrophages, and it participates in shaping adaptive immune responses.

Clinical relevance includes its role in transplantation immunology, where HLA typing often considers DRB1 along with DRB3/4/5 alleles to improve donor–recipient matching and reduce alloreactivity. Associations between DRB3 alleles and susceptibility or resistance to certain autoimmune or infectious diseases have been reported in population studies, though findings are complex and often context-dependent.