Biological evaluation of multivalent Lewis X-MGL-1 interactions

M. Eriksson, S. Serna, M. Maglinao, M.K. Schlegel, P.H. Seeberger, N.C. Reichardt, B. Lepenies – 2014

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.

Titel
Biological evaluation of multivalent Lewis X-MGL-1 interactions
Verfasser
M. Eriksson, S. Serna, M. Maglinao, M.K. Schlegel, P.H. Seeberger, N.C. Reichardt, B. Lepenies
Datum
2014
Kennung
DOI: 10.1002/cbic.201300764
Zitierweise
ChemBioChem 2014, 15(6): 844-51
Art
Text
dfg_logo