For the first time researchers at Utrecht University and Leiden University Medical Center, the Netherlands, have visualized an important on-switch of our immune system.A novel technical approach led to the discovery of not one, but two ways in which the immune system can be activated: by physical distortion and by cross-activation. In some cases, the configuration of danger signals on a cell’s surface is sparse, and when antibodies bind, the entire complex must physically adjust or distort itself to properly fit. This adjustment of a single complex can set off an immune response. In other situations, where the danger signals are dense, multiple C1 complexes can help activate each other, like a neighbourhood watch system.
This kind of new insights are important for designing better therapies against infections or cancer. The findings are published on February 16, 2018 in the journal Science.
Ugurlar D, Howes SC, de Kreuk BJ, Koning RI, de Jong RN, Beurskens FJ, Schuurman J, Koster AJ, Sharp TH, Parren PWHI, Gros P. Structures of C1-IgG1 provide insights into how danger pattern recognition activates complement. Science. 2018 Feb 16;359(6377):794-797.
Read more about the research in the press release on the LUMC website.
Image: Life-like detailed picture: Combining CryoEM and CryoET lets researchers see the C1 complex in 3D (colored model) bound to antibodies in a native state (background).