Immunoglobulin G (IgG) represents the most abundant antibody class in the human circulation. IgG consists of two heavy chains and two light chains. Parts of the heavy chains, together with the... Show moreImmunoglobulin G (IgG) represents the most abundant antibody class in the human circulation. IgG consists of two heavy chains and two light chains. Parts of the heavy chains, together with the light chains, form two fragment antigen binding (Fab) moieties, whilst the remainders of the two heavy chains form the fragment crystallizable (Fc) moiety. Human IgGs are glycosylated at the highly conserved N-glycosylation site asparagine 297 in the CH2 domain of each heavy polypeptide chain of the Fc part. Fully galactosylated N-glycans are positioned between the Fc polypeptide chains, resulting in an open Fc conformation which is required for high affinity binding to Fc_ receptors. Small changes in the Fc glycosylation can already have a profound influence on the interaction of the Fc portion with receptors modulating the anti and pro-inflammatory properties of IgG. Mass spectrometry provides great opportunities for deta iled structural characterization of protein glycosylation including protein identification, determination of site-specific glycosylation profiles, and structural characterization of glycans at the level of released glycans and glycopeptides. In this thesis novel approaches for fast, miniaturized and high-throughput analysis of IgG Fc N-glycosylation are presented, and the utility of these methods has been demonstrated for clinically relevant research questions. Show less
Selman, M.H.J.; Derks, R.J.E.; Bondt, A.; Palmblad, M.; Schoenmaker, B.; Koeleman, C.A.M.; ... ; Wuhrer, M. 2012
