Abstract 1477 Mapping affinity and allostery of human IgG antibody Fc region interactions with endoglycosidases, and comparison of fucosylated/afucosylated Fc region interactions with activating and inhibitory Fc γ Receptors

The Fc regions of IgG antibodies modulate appropriate immune responses for given antigens through binding to cell surface receptors and effector molecules. This modulation ability depends both on Fc glycosylation patterns and, to a lesser extent, on the amino acid sequence. Endoglycosidases such as EndoS2, CU43 and CM49, can indirectly tune immune response through chemoenzymatic cleavage of certain glycosylated Fc regions. These cleavages depend on the Fc-endoglycosidase interaction patterns, and therefore we conducted a high-throughput analysis of such binding interactions between selected endoglycosidases and Fc variants covering more than 98% of all possible single-site amino acid substitutions.