Publications by authors named "Venice C M Broks-van den Berg"

2 Publications

  • Page 1 of 1

The C-type lectin macrophage galactose-type lectin impedes migration of immature APCs.

J Immunol 2008 Sep;181(5):3148-55

Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.

Dendritic cells (DCs) are the most potent APCs of the immune system that seed the peripheral tissues and lymphoid organs. In an immature state, DCs sample their surroundings for incoming pathogens. Upon Ag encounter, DCs mature and migrate to the lymph node to induce adaptive immune responses. The C-type macrophage galactose-type lectin (MGL), expressed in immature DCs, mediates binding to glycoproteins carrying GalNAc moieties. In the present study, we demonstrate that MGL ligands are present on the sinusoidal and lymphatic endothelium of lymph node and thymus, respectively. MGL binding strongly correlated with the expression of the preferred MGL ligand, alpha-GalNAc-containing glycan structures, as visualized by staining with the alpha-GalNAc-specific snail lectin Helix pomatia agglutinin. MGL(+) cells were localized in close proximity of the endothelial structures that express the MGL ligand. Strikingly, instead of inducing migration, MGL mediated retention of human immature DCs, as blockade of MGL interactions enhanced DC trafficking and migration. Thus, MGL(+) DCs are hampered in their migratory responses and only upon maturation, when MGL expression is abolished; these DCs will be released from their MGL-mediated restraints.
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September 2008

MGL-mediated internalization and antigen presentation by dendritic cells: a role for tyrosine-5.

Eur J Immunol 2007 Aug;37(8):2075-81

Department of Molecular Cell Biology & Immunology, VU University Medical Center, Amsterdam, The Netherlands.

Professional antigen-presenting cells are essential for the initiation of adaptive immune responses; however, they also play a vital role in the maintenance of tolerance towards self-antigens. C-type lectins can function as antigen receptors by capturing carbohydrate ligands for processing and presentation. Here, we focused on the dendritic cell (DC)-expressed macrophage galactose-type lectin (MGL), a C-type lectin with a unique specificity for terminal GalNAc residues, such as the tumor-associated Tn antigen. Soluble model antigens are efficiently internalized by MGL and subsequently presented to responder CD4+ T cells. The tyrosine-5 residue in the YENF motif, present in the MGL cytoplasmic domain, was essential for the MGL-mediated endocytosis in CHO cells. In conclusion, MGL contributes to the antigen processing and presentation capacities of DC and may provide a suitable target for the initiation of anti-tumor immune responses.
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August 2007