Structure and function of antibodies
Antibodies represent the quintessential effector molecules of the adaptive immune system. They display tremendous variation in structure, allowing the immune system to quickly adapt to invading pathogens, recognizing a virtually unlimited number of structures, and combining this with a large variety of functional traits in a modular fashion. Antibodies have also been exploited successfully as therapeutic agents, resulting in highly selective and powerful treatments that dramatically changed the lives of millions of patients treated with e.g. TNF inhibitors. An ever increasing list of approved therapeutic antibodies emphasizes not only the versatility of antibodies as therapeutic agents, but also the continued need to investigate antibody structure and function in its various facets. Although intensively studied, the basic biology of immunoglobulins is still incompletely understood, precisely because of their large structural variation and the potential to interact with so many other parts of the immune system.
Our research addresses one central aim: unraveling the mechanisms of (lack of) regulation by antibodies in pathological and clinical setting. In this context, we focus in particular on non-infectious antigens. In order to achieve this, we develop biophysical and immunochemical methodology to investigate structure-function relationships of antibodies in a basic and clinical setting. The research is centered around four interconnected themes: 1) Biologics. We aim to arrive at personalized medicine with therapeutic antibodies, dissect the development of humoral tolerance to biologics, and characterization of anti-idiotype responses. 2) Biology of IgG4 (together with M. van Ham) see Antigen specific B cell responses. We are interested in the question how IgG4-specific properties contribute to humoral tolerance or the lack thereof, and how do IgG4/Th2 responses develop and how they can be avoided (e.g. in case of anti-biological responses)? 3) Antibodies to antibodies in RA. We investigate the role of rheumatoid factors and anti-hinge antibodies in RA. 4) The role of Fab glycosylation in the humoral immune response, and the potential contribution of Fab glycans to the immunomodulatory properties of IVIg.
- Dutch Arthritis Foundation
- ZonMw, Netherlands Research Council
- Health Holland
- Hersenstichting (Brain foundation of the Netherlands)
- Product and Process Development Diagnostic Services/Reagents (PPODR Internal funding in competition)