HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1) (HLA-DRB1)

HLA class II molecules, specifically the HLA-DRB1 gene products, are cell surface glycoproteins that play a pivotal role in the adaptive immune system by presenting processed antigenic peptides to CD4+ T cells (UniProt P01911). In rheumatoid arthritis (RA), certain HLA-DRB1 alleles carry a specific five-amino acid sequence known as the 'shared epitope' (SE), which is the most significant genetic risk factor for the development of the disease (Gregersen et al., 1987, Arthritis & Rheumatism). These SE-positive molecules have a high affinity for citrullinated peptides, leading to the activation of autoreactive T cells and the production of anti-citrullinated protein antibodies (ACPA), which drive chronic joint inflammation and bone destruction (Holoshitz, 2010, Annals of the Rheumatic Diseases). Therapeutic interventions often target the downstream consequences of this interaction, such as abatacept, which blocks the costimulatory signals required for T-cell activation by the HLA-peptide complex (FDA, Orencia Prescribing Information). Research is also ongoing into antigen-specific therapies, such as Rheumavax, that aim to induce immune tolerance by specifically targeting the HLA-DRB1-mediated presentation of arthritogenic peptides (Ben-Amos et al., 2017, JCI Insight).

Other names

MHC class II antigen DRB1Shared Epitope (SE) allelesHLA-DRBHuman leukocyte antigen DR beta 1DR beta-1 chain

T-cell costimulation modulation and inhibition of antigen-specific T-cell activation by blocking the interaction between antigen-presenting cells and T-cells.