Biological Evaluation of Multivalent Lewis X–MGL‐1 Interactions |
| |
Authors: | Dr Magdalena Eriksson Dr Sonia Serna Dr Maha Maglinao Dr Mark K Schlegel Prof Dr Peter H Seeberger Dr Niels‐Christian Reichardt Dr Bernd Lepenies |
| |
Affiliation: | 1. Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam (Germany);2. Institute for Chemistry and Biochemistry, Freie Universit?t Berlin, Arnimallee 22, 14195 Berlin (Germany);3. Biofunctional Nanomaterials Unit, CICbiomaGUNE, Paseo Miramon 182, 20009 San Sebastian (Spain);4. CIBER‐BBN, Paseo Miramon 182, 20009 San Sebastian (Spain) |
| |
Abstract: | Myeloid C‐type lectin receptors (CLRs) expressed by antigen‐presenting cells are pattern‐recognition receptors involved in the recognition of pathogens as well as of self‐antigens. The interaction of carbohydrate ligands with a CLR can trigger immune responses. Although several CLR ligands are known, there is limited insight into CLR targeting by carbohydrate ligands. The weak affinity of lectin–carbohydrate interactions often renders multivalent carbohydrate presentation necessary. Here, we have analyzed the impact of multivalent presentation of the trisaccharide Lewis X (LeX) epitope on its interaction with the CLR macrophage galactose‐type lectin‐1 (MGL‐1). Glycan arrays, including N‐glycan structures with terminal LeX, were prepared by enzymatic extension of immobilized synthetic core structures with two recombinant glycosyltransferases. Incubation of arrays with an MGL‐1‐hFc fusion protein showed up to tenfold increased binding to multiantennary N‐glycans displaying LeX structures, compared to monovalent LeX trisaccharide. Multivalent presentation of LeX on the model antigen ovalbumin (OVA) led to increased cytokine production in a dendritic cell /T cell coculture system. Furthermore, immunization of mice with LeX‐OVA conjugates modulated cytokine production and the humoral response, compared to OVA alone. This study provides insights into how multivalent carbohydrate–lectin interactions can be exploited to modulate immune responses. |
| |
Keywords: | antigens carbohydrates C‐type lectins dendritic cells multivalency targeting |
|
|