How antibody type and bacterial antigens influence complement activation

Abstract

Antibodies play an important role in the anti-bacterial immune defence. One of these roles is the activation of the complement system, which is of major importance in antibacterial immun-ity. There are several aspects which determine how well an antibody can activate the comple-ment system, which we discuss in this review. Here, the different antibody isotypes display distinct characteristics based on their size and structure, with IgG and IgM being the most potent complement activators. For instance, IgM is secreted as a pentamer or hexamer and has thus high avidity compared to IgG, which is secreted as a monomer. However, IgG can target more specific antigens and can reach more concealed antigens due to its smaller size. The size of the antibodies also influences their interactions with other proteins and antibodies, with larger an-tibodies like IgG3 being more accessible to other proteins like the complement protein C1q than the smaller IgG1, but at the same time also being less rigid. The differences between antibody isotypes and subclasses allows them to target different bacterial antigens. IgM with its high avidity and bigger size may be better suited to target larger, more exposed and more variable antigens like CPS and LPS, whereas IgG antibodies may be advantageous in targeting more specific, less protruding antigens like OMPs. Taken together, a complex interplay between an-tibody characteristics, determined by their size and structure, and bacterial antigen characteris-tics, like availability and density, influence how efficient an antibody can activate the comple-ment system in response to bacterial infection.