HLA class II histocompatibility antigen, DRB1-4 beta chain (HLA-DRB1*04:01) (HLA-DRB1*04:01)

HLA-DRB1*04:01 is a specific allele of the human leukocyte antigen (HLA) class II beta chain, which forms a heterodimer with the HLA-DRA chain to create the HLA-DR receptor (UniProt P01911). This molecule is primarily expressed on the surface of professional antigen-presenting cells, such as dendritic cells and B cells. Its primary biological function is the presentation of exogenous peptides to CD4+ T-helper cells, a critical step in the initiation of the adaptive immune response. The peptide-binding groove of the HLA-DRB1*04:01 allele is characterized by a specific sequence known as the "shared epitope," which is highly associated with an increased risk and severity of rheumatoid arthritis (Gregersen et al., 1987). In autoimmune contexts, this groove binds and presents self-antigens, such as citrullinated proteins, leading to the loss of self-tolerance and chronic inflammation (Scally et al., 2013). Therapeutic strategies targeting this groove aim to block the presentation of these pathogenic peptides or induce immune tolerance through the use of altered peptide ligands or small molecule inhibitors (Benham et al., 2015).

Other names

MHC class II antigen DRB1*0401DR4Shared Epitope-positive HLA-DRB1HLA-DRB1*04:01 peptide-binding groove

Competitive inhibition of the peptide-binding groove to prevent the presentation of arthritogenic self-antigens to CD4+ T cells, thereby reducing autoimmune activation.