Detailed understandings of the molecular interactions that regulate antibody function have afforded investigators the ability to design fit-for-purpose antibody-based therapeutics.
The CH1-CH2 domais is responsible for FcγR binding, which is critical for antibody effector functions (Daëron, 2014; Jefferis & Lund, 2002).
While the biantennary complex-type oligosaccharide attached to Asn297 of the Fc is essential for antibody effector functions, fucose and outer-arm sugars attached to the core heptasaccharide that generate structural heterogeneity (glycoforms) exhibit unique biological activities.
We provide novel information about bacterial enzymatic modulation of the IgG/FcγR interaction that emphasizes the importance of glycosylation for antibody effector functions.
They contain an N-linked oligosaccharide attached to the second heavy-chain constant domain (CH2) that is essential for antibody effector functions such as antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytolysis (CDC), and for retaining a long serum half-life.
For many applications, however, it is useful to restore Fc mediated antibody functions such as avidity, effector functions and a prolonged serum half-life.
Comprised of the CH2 and CH3 domains, the Fc region is important not only for the antibody effector function but also for its long half-life.
First of all, we screened several commercially available anti-human VEGF-C antibodies for function blocking activity and found that a polyclonal goat antibody raised against the C terminus of VEGF-C of human origin (Santa Cruz, CA, USA) was active, similar to its blocking activity reported on coronary endothelial tube formation from embryonic cardiac explants (Tomanek et al, 2002).
These results provide novel information about the mechanisms behind enzymatic modulation of the host immune defense by bacteria, provide novel information about the molecular interactions between an IgG glycan-hydrolyzing enzyme and IgG, and emphasize the importance of IgG glycosylation for correct antibody effector functions.
