Human leukocyte antigen DR15 (HLA-DR15) (HLA-DR15)

Human leukocyte antigen DR15 (HLA-DR15) is a specific isotype of the major histocompatibility complex (MHC) class II receptor, primarily expressed on professional antigen-presenting cells such as B cells, macrophages, and dendritic cells. It is a heterodimer composed of an alpha chain (DRA) and a beta chain (DRB1*15:01) that together form a peptide-binding groove responsible for presenting processed exogenous antigens to CD4+ T helper cells (UniProt: P01911). This molecule is clinically significant as the strongest genetic risk factor for multiple sclerosis (MS), where it is believed to present myelin-derived autoantigens, such as myelin basic protein (MBP), to autoreactive T cells, triggering neuroinflammation (PubMed: 12637953). Beyond MS, HLA-DR15 is associated with other autoimmune conditions, including Goodpasture syndrome and systemic lupus erythematosus, as well as protection against certain infections. Therapeutic strategies targeting the HLA-DR15 peptide-binding groove aim to block the presentation of autoantigens or induce immune tolerance through competitive binding. Drugs like glatiramer acetate are thought to interact with this groove to shift the immune response from a pro-inflammatory to an anti-inflammatory state (PubMed: 15546724).

Other names

HLA-DRB1*15:01MHC class II DR15HLA-DR2Major histocompatibility complex, class II, DR beta 1DR15

Competitive binding to the MHC class II peptide-binding groove to displace autoantigenic peptides and modulate T-cell activation from a Th1/Th17 phenotype to a regulatory or Th2 phenotype.