Targeting of macrophage galactose‐type C‐type lectin (MGL) induces DC signaling and activation
- 24 April 2012
- journal article
- Published by Wiley in European Journal of Immunology
- Vol. 42 (4), 936-945
- https://doi.org/10.1002/eji.201142086
Abstract
Dendritic cells (DCs) sense the microenvironment through several types of receptors recognizing pathogen‐associated molecular patterns. In particular, C‐type lectins, expressed by distinct subsets of DCs, recognize and internalize specific carbohydrate antigen in a Ca2+‐dependent manner. Targeting of these receptors is becoming an efficient strategy of delivering antigens in DC‐based anticancer immunotherapy. Here we investigated the role of the macrophage galactose type C‐lectin receptor (MGL), expressed by immature DCs (iDCs), as a molecular target for α‐N‐acetylgalactosamine (GalNAc or Tn)‐carrying tumor‐associated antigens to improve DC performance. MGL expressed by ex vivo‐generated iDCs from healthy donors was engaged by a 60‐mer MUC19Tn‐glycopeptide as a Tn‐carrying tumor‐associated antigen, and an anti‐MGL antibody, as a specific MGL binder. We demonstrated that MGL engagement induced homotrimers and homodimers, triggering the phosphorylation of extracellular signal‐regulated kinase 1,2 (ERK1,2) and nuclear factor‐κB activation. Analysis of DC phenotype and function demonstrated that MGL engagement improved DC performance as antigen‐presenting cells, promoting the upregulation of maturation markers, a decrease in phagocytosis, an enhancement of motility, and most importantly an increase in antigen‐specific CD8+T‐cell activation. These results demonstrate that the targeting of MGL receptor on human DCs has an adjuvant effect and that this strategy can be used to design novel anticancer vaccines.Keywords
This publication has 41 references indexed in Scilit:
- Recent Developments in Cancer VaccinesThe Journal of Immunology, 2011
- Design of neo‐glycoconjugates that target the mannose receptor and enhance TLR‐independent cross‐presentation and Th1 polarizationEuropean Journal of Immunology, 2011
- Concomitant Activation and Antigen Uptake via Human Dectin-1 Results in Potent Antigen-Specific CD8+ T Cell ResponsesThe Journal of Immunology, 2010
- Distribution and Function of Macrophage Galactose-type C-type Lectin 2 (MGL2/CD301b)Online Journal of Public Health Informatics, 2010
- Epidermal Langerhans Cells Rapidly Capture and Present Antigens from C-Type Lectin-Targeting Antibodies Deposited in the DermisJournal of Investigative Dermatology, 2010
- Variation of Neisseria gonorrhoeae Lipooligosaccharide Directs Dendritic Cell–Induced T Helper ResponsesPLoS Pathogens, 2009
- MGL2+ Dermal Dendritic Cells Are Sufficient to Initiate Contact Hypersensitivity In VivoPLOS ONE, 2009
- MGL‐mediated internalization and antigen presentation by dendritic cells: A role for tyrosine‐5European Journal of Immunology, 2007
- Qualitatively distinct patterns of cytokines are released by human dendritic cells in response to different pathogensImmunology, 2005
- Substrate Specificities of Three Members of the Human UDP-N-Acetyl-α-d-galactosamine:Polypeptide N-Acetylgalactosaminyltransferase Family, GalNAc-T1, -T2, and -T3Online Journal of Public Health Informatics, 1997