DRB4

DRB4 is a gene located in the human major histocompatibility complex (MHC) class II region on chromosome 6p21.3. It encodes the beta chain of the HLA-DR class II molecule, which forms a heterodimer with the alpha chain encoded by HLA-DRA. The resulting HLA-DR molecule is responsible for presenting extracellular protein-derived peptides to CD4+ T cells, an essential step in initiating and regulating adaptive immune responses.

The DRB4 gene is one of several DRB genes that provide beta-chain diversity for HLA-DR receptors, along with DRB1, DRB3, and DRB5. DRB4 is highly polymorphic, with multiple alleles in the human population. Expression of DRB4-derived beta chains is often linked to specific HLA haplotypes, so not all individuals express the DRB4 product in all tissues.

In the antigen presentation pathway, peptides loaded onto HLA-DR molecules are derived from endosomal/lysosomal processing of extracellular proteins. The loading process involves molecular chaperones and accessory factors such as the invariant chain, HLA-DM, and others, which influence the repertoire of peptides presented by DRB4-containing molecules. The particular peptide-binding properties depend on the specific DRB4 allele.

Clinical relevance is broader for HLA class II genes, as variation across these loci influences immune responses and can be associated with disease susceptibility or transplantation outcomes in some contexts. DRB4 is frequently considered in HLA typing and research on immune function, autoimmune disease, and infectious disease responses, though DRB4-specific associations are less extensively characterized than those for some other HLA-DR genes. See also HLA-DRA, HLA-DRB1, and the broader HLA class II region.