Major histocompatibility complex class II, HLA-DRB1*04:01 (HLA-DRB1*04:01)

Major histocompatibility complex class II, HLA-DRB1*04:01 is a specific allele of the HLA-DRB1 gene, which encodes the beta chain of the HLA-DR heterodimer, a critical component of the MHC class II system [1.3.2]. This molecule is primarily expressed on the surface of professional antigen-presenting cells, where it presents exogenous peptides to CD4+ T helper cells to initiate adaptive immune responses [1.3.4]. HLA-DRB1*04:01 is most notably recognized as the primary genetic risk factor for Rheumatoid Arthritis (RA), characterized by the 'shared epitope'—a specific amino acid sequence (QKRAA) in the peptide-binding groove that facilitates the presentation of citrullinated self-antigens, leading to autoimmunity [1.1.3, 1.2.5]. Beyond RA, it is associated with susceptibility to Type 1 Diabetes and Multiple Sclerosis, while recent research suggests a protective role in neurodegenerative diseases like Alzheimer's and Parkinson's by promoting the clearance of pathological tau proteins [1.1.1, 1.3.1]. Therapeutic interventions targeting this molecule include T-cell costimulation blockers like Abatacept, which indirectly modulate the MHC-TCR interaction, and experimental approaches such as peptide-based tolerogenic vaccines and CRISPR-mediated gene editing of the shared epitope [1.1.5, 1.2.4].

Other names

HLA-DRB1*04:01DR4DRB1*0401MHC class II antigen DRB1*04:01Shared epitope-positive HLA-DRB1HLA class II histocompatibility antigen, DRB1 beta chain

HLA-DRB1*04:01 functions by binding and presenting antigenic peptides to T-cell receptors (TCRs). Drugs like Abatacept interact with this pathway by binding to CD80/CD86 on antigen-presenting cells, thereby preventing the costimulatory signal required for T-cell activation following MHC-peptide-TCR binding [1.2.4]. Experimental therapies like Rheumavax utilize specific peptides to induce immune tolerance or block the peptide-binding groove [1.1.5, 1.2.5].