Schematic illustration of the engineered antibodies. (A-B) Schematic illustrations of the domain architecture of wild-type IgG1 and IgG3. (C-D) The 2 engineered IgG3 antibodies, IgG3ΔHinge and IgG3ΔHinge:R435H, both have a deletion of the hinge region and a mutation within the C_H1 domain (C131S), making them unable to activate complement and FcγR-mediated functions, which are the 2 main effector systems leading to cellular destruction. Compared with IgG3ΔHinge, the IgG3ΔHinge:R435H antibody has a mutation in the C_H3 domain of the Fc where an arginine at position 435 is exchanged to a histidine, making IgG3ΔHinge:R435H identical to IgG1 in this position.