Glycobiology as immune response modulator

Glycans are complex carbohydrate structures that cover the surfaces of all mammalian cells, as they are added to proteins- and lipid backbones by the so-called glycosylation machinery enzymes, present in every cell. Glycans are the outer part of glycoproteins and form recognition elements for glycan sensor molecules that, upon recognition, mediate cellular communication. Glycan recognition is playing a crucial role in cellular communication between immune cells. Dendritic cells (DCs) that are instrumental in stimulating or inhibiting immune responses express many glycan sensor molecules. These glycan sensor molecules (called lectins) recognize specific glycans and can thereby instruct tailor made immune responses. Recognition of glycans on pathogens by dendritic cells can initiate immunological defense.

At DC4U, we focus on the immunological importance of glycans since they can act as mediators in the interactions between host and invading pathogen, and between host and self-antigens.

glycobiologyGlycans can be covalently attached to any protein or lipid molecule of choice, a process called glycation. Our technology is based on glycation of antigens which can be proteins or peptides derived from macromolecules to which we direct the immune response. Alternatively we couple glycans to delivery systems (such as lipids) that contain encapsulated antigen, for targeting specificity. Specific glycan structures can be recognized by unique receptors, present on DCs.

One of the best-studied receptors on these antigen-presenting cells is DC-SIGN, originally identified by our CSO Prof. Yvette van Kooyk. DCs continuously sample the body for the presence of disease-causing agents. Upon encounter, DCs recognize and take up the pathogen using its glycan sensing receptors. Fragments of the ingested pathogen are then presented to T cells. In an interactive process between the two cell types, DCs instruct the T cells to build up a response aimed to eradicate the particular pathogen. On the other hand DCs can also recognize inhibitory glycans with unique receptors that instruct T cells to dampen immune responses. The recognition of specific glycans by DCs therefore plays a crucial decision making role to either activate or inhibit an immune reaction. Recent studies from the van Kooyk group have shown that the T cell stimulatory and inhibitory activity of DCs can be modulated by specifically targeting DC receptors with glycan structures linked to antigens or allergens.