Nanoscale spatial dependence of avidity in an IgG1 antibody
Agnieszka Jendroszek and Magnus Kjaergaard
Received Date: 21st May 19
Antibodies are secreted proteins that are crucial to recognition of pathogens by the immunesystem and are also efficient pharmaceuticals. The affinity and specificity of targetrecognition can increase remarkably through avidity effects, when the antibody can bind amultivalent antigen though more than one epitope simultaneously. A key goal of antibodyengineering is thus to optimize avidity, but little is known about the nanoscale spatialdependence of avidity in antibodies. Here, we develop a set of anti-parallel coiled-coilsspanning from 7-20 nm and validate their structure using biophysical techniques. We usethe coiled-coils to control the spacing between two epitopes, and measure how antigenspacing affects the stability of the bivalent antibody:antigen complex. We find a maximalavidity enhancement at a spacing of 13 nm. In contrast to recent studies, we find the avidityto be relatively insensitive to epitope spacing near the avidity maximum as long as it is withinthe spatial tolerance of the antibody. We thus only see a ~2-fold variation of avidity in therange from 7-20 nm. The coiled-coil systems developed here may prove a useful proteinnanocaliper for profiling the spatial tolerance and avidity profile of bispecific antibodies.
Read in full at bioRxiv.
This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.