IgG Subclass Glycosylation

Immunoglobulin Gs (IgG) are antibodies (Ab) in human blood, which play a central role in eliminating invaders. These molecules are proteins which carry a modification, namely sugar residues. These glycans, as they were also called, were ignored for a long time by the researchers, who concentrated mainly on the protein itself, if the function of IgGs were explored. In recent years, however, it has become increasingly clear that this modification has a significant influence on the Abs activities, thus their investigation has become an important scientific issue. This is mainly due to the fact that Ab-based therapies are among the most important innovations in drug development in the recent 10 years. The main goal of this project is the investigation of the influence of glycans on the activity of IgG antibodies. In human serum 4 subtypes (IgG1-4) are present, whereby the knowledge about activities of the subtypes 2-4 is largely unknown. To ensure comprehensive research the complementary expertise of two leading scientists in the field of antibody research, namely Falk Nimmerjahn (Friedrich-Alexander-Universität Erlangen, Germany) and Herta Steinkellner (BOKU-WIEN), have been brought together. Steinkellner developed a unique method by which the IgG subtypes can be produced in the laboratory carrying targeted glycan profiles, one of the major challenges in glycobiological research. Nimmerjahn developed an animal model, with which the effects of IgGs can be investigated in a close to human manner. This system is based on molecular biologically modified mice that have a human immune system. This enables innovative IgG functional studies with high human relevance. Antibodies which are already used for the treatment of cancer are used as models for the deciphering of the glycan-based IgG function. Results are expected that provide a new understanding of glycan-dependent immunological processes. The joint efforts could lead to a paradigm shift in the development of new antibody therapeutics.

Immunoglobulin Gs (IgG) are antibodies (Ab) in human blood that play a central role in fighting invaders. These molecules are proteins that carry a modification, namely sugar residues. These glycans, as they are also called, can change the function of the Abs. The main goal of this project is to investigate the influence of glycans on the mode of action of IgG antibodies. In human serum, these are present in 4 subtypes (IgG1-4), with little knowledge about the activities of subtypes 2-4. The complementary expertise of two leading scientists in the field of antibody research, namely Falk Nimmerjahn (Friedrich-Alexander-University Erlangen, Germany) and Herta Steinkellner (BOKU-WIEN) were brought together. Steinkellner developed a unique processfor the production of IgG subtypes with targeted glycan patterns. Nimmerjahn developed an animal model with which the effects of IgGs can be examined as closely as possible to humans. The investigations have shown that certain sugar structures have major effects, but most importantly, hitherto neglected Ab types (namely IgG3 and IgA) could be produced in such a way that they had a so far unknown high activity. The results were published in several high-profile journals and the collaborations between the two groups were further pursued.