Thesis defense Sanne van de Bovenkamp
The role of variable domain glycosylation of antibodies in immunity News
On 7 May 2019 (10:00) Sanne van de Bovenkamp will defend her thesis at the University of Amsterdam. During her PhD research Sanne found a possible immunomodulatory role for Fab glycans in immunity which could eventually contribute to improve antibody therapies.
Immunoglobulin G (IgG) is the most abundant class of immunoglobulins in the blood, and 15-25% of IgG molecules contain Fab glycans in addition to the Fc glycans that are present in all IgG molecules. The emergence of Fab-glycosylated antibodies, starting from largely absent in the initial antibody repertoire of naive B cells, was mostly unexplored.
Antigen-associated selection
During her PhD research Sanne found that Fab glycosylation sites mainly emerge near the antigen-binding site, explaining the potential of Fab glycans to influence antigen binding. The differences in Fab glycosylation between antigen specificities indicate antigen-associated selection.
In addition to their influence on antigen binding, we found that Fab glycans can contribute to antibody stability. Our results suggest that Fab glycans are exposed to different degrees, possibly explaining why some Fab glycans do have an effect on antigen binding and/or antibody stability and others do not.
Immune modulation
IgG4 antibody responses are associated with tolerance, and the increased Fab glycosylation of this subclass might suggest a role for Fab glycans in immune modulation. Interestingly, our preliminary in vivo experiments indicate that Fab glycosylated drug antibodies are less immunogenic than drug antibodies without Fab glycans, again suggesting a role for Fab glycans in immune modulation.
Together, the results presented in this thesis show that Fab glycans can affect antigen binding and antibody stability, and our findings suggest that future research on the possible immunomodulatory role for Fab glycans in immunity could be very useful and eventually possibly contribute to improve antibody therapies.
- Promotor: Prof. Dr. S.M. van Ham
- Copromotores: Dr. T. Rispens Dr. G. Vidarsson
- Location: University of Amsterdam, Agnietenkapel
