Targeting glycan modified OVA to murine DC-SIGN transgenic dendritic cells enhances MHC class I and II presentation
| Autor: | Tim Sparwasser, Eirikur Saeland, Joke M. M. den Haan, Hakan Kalay, Johannes Stephani, Martin Schaefer, Yvette van Kooyk, Juan J. Garcia-Vallejo, Satwinder Kaur Singh |
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| Přispěvatelé: | CCA - Immuno-pathogenesis, NCA - Multiple Sclerosis and Other Neuroinflammatory Diseases, Molecular cell biology and Immunology |
| Rok vydání: | 2009 |
| Předmět: |
Genetically modified mouse
CD4-Positive T-Lymphocytes Glycan Ovalbumin Transgene Immunology Antigen presentation Lewis X Antigen Bone Marrow Cells Mice Transgenic Receptors Cell Surface CD8-Positive T-Lymphocytes Mice Cross-Priming Antigen Polysaccharides MHC class I Cytotoxic T cell Animals Humans Lectins C-Type Molecular Biology Antigen Presentation biology Histocompatibility Antigens Class I Histocompatibility Antigens Class II Dendritic Cells Molecular biology Cell biology DC-SIGN Mice Inbred C57BL biology.protein Carbohydrate Metabolism Cell Adhesion Molecules Glycoconjugates |
| Zdroj: | Singh, S K, Stephani, J, Schaefer, M, Kalay, H, Garcia Vallejo, J J, den Haan, J M M, Saeland, E, Sparwasser, T & van Kooyk, Y 2009, ' Targeting glycan modified OVA to murine DC-SIGN transgenic dendritic cells enhances MHC class I and II presentation ', Molecular Immunology, vol. 47, no. 2-3, pp. 164-174 . https://doi.org/10.1016/j.molimm.2009.09.026 Molecular Immunology, 47(2-3), 164-174. Elsevier Limited |
| ISSN: | 0161-5890 |
| Popis: | Dendritic cells have gained much interest in the field of anti-cancer vaccine development because of their central function in immune regulation. One of the receptors that facilitate DC-specific targeting of antigens is the DC-specific C-type lectin DC-SIGN. Although DC-SIGN is specifically expressed on human DCs, its murine homologue is not present on any murine DC subsets, which makes in vivo evaluation of potential DC-SIGN targeting vaccines very difficult. Here we describe the use of DC-SIGN transgenic mice, as a good model system to evaluate DC-SIGN targeting vaccines. We demonstrate that glycan modification of OVA with DC-SIGN targeting glycans, targets antigen specifically to bone marrow (BM)** derived DCs and splenic DCs. Glycan modification of OVA with Lewis X or Lewis B oligosaccharides, that target DC-SIGN transgenic DCs, resulted in efficient 10-fold induction of OT-II compared to unmodified OVA. Interestingly, glycan modified OVA proteins were significantly cross-presented to OT-I T cells by wild type DC, 10-fold more than native OVA, and the expression of DC-SIGN further enhanced this cross-presentation. Targeting of glycosylated OVA was neither accompanied with any DC maturation, nor the production of inflammatory or anti-inflammatory cytokines. Thus, we conclude that glycan modification of antigens and targeting to DC-SIGN enhance both CD4 and CD8 T cell responses. Furthermore, our data demonstrate that DC-SIGN transgenic mice are valuable tool for optimisation and efficiency testing of DC vaccination strategies that are designed to target in particular the human DC-SIGN receptor. |
| Databáze: | OpenAIRE |
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