Abstract 1910 Histidine Substitutions within Antibody Interfaces to Create pH-Dependent Interactions

Antibodies that exhibit pH-dependent binding to their antigen can provide valuable functions for therapeutic applications, including sweeping antibodies and tumor targeting. Consequently, new methods to engineer pH-dependent antibodies, along with understanding the fundamental driving forces, are of interest. Here, we examine two model antibody systems, an anti-caffeine VHH and an anti-MBP Fab, to evaluate how histidine residues can serve as ionizable triggers to produce pH-dependent binding, including their introduction within the homodimeric VHH interface of the anti-caffeine VHH or within the Fab/MBP (antigen) binding interface.