New understanding of HLA-mediated susceptibility and protection in a rare, autoimmune renal disorder may help deliver new therapies for more common autoimmune diseases such as type 1 diabetes, multiple sclerosis and Crohn’s disease.
Australian-led research published in Nature identified Goodpasture’s disease as a simple ‘model’ of autoimmune disease. It has a single dominant autoantigen within type IV collagen and the HLA associations are well described, with HLA-DR15 conferring an increased risk of disease and HLA-DR1 being protective.
Co-senior author Professor Richard Kitching, director of the Monash Centre for Inflammatory Diseases, said DR1 is dominantly protective against Goodpasture’s disease in the presence of DR15.
“In Goodpasture’s disease when the molecule DR15 is present it can select and instruct T cells to attack the body,” he told the limbic. “But when people also have the protective DR1 molecule, these T cells are held at bay and can be overturned.”
Professor Kitching said their study showed DR1 can generate epitope-specific regulatory T cells, which help suppress the autoreactive cells.
They identified structural differences in the DR15 and DR1-alpha3135-145 peptide complexes that change the way the immune system ‘sees’ the autoantigen and are critical to the way the immune system selects antigen specific T cells.