Enhanced Cross-Presentation and Improved CD8+ T Cell Responses after Mannosylation of Synthetic Long Peptides in Mice |
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| Authors: | Judith Rauen Christoph Kreer Arlette Paillard Suzanne van Duikeren Willemien E Benckhuijsen Marcel G Camps A Rob P M Valentijn Ferry Ossendorp Jan W Drijfhout Ramon Arens Sven Burgdorf |
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| Institution: | 1. Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.; 2. Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.; 3. Department of Bio-organic Synthesis, Leiden University Medical Center, Leiden, the Netherlands.; MRC National Institute for Medical Research, United Kingdom, |
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| Abstract: | The use of synthetic long peptides (SLP) has been proven to be a promising approach to induce adaptive immune responses in vaccination strategies. Here, we analyzed whether the efficiency to activate cytotoxic T cells by SLP-based vaccinations can be increased by conjugating SLPs to mannose residues. We could demonstrate that mannosylation of SLPs results in increased internalization by the mannose receptor (MR) on murine antigen-presenting cells. MR-mediated internalization targeted the mannosylated SLPs into early endosomes, from where they were cross-presented very efficiently compared to non-mannosylated SLPs. The influence of SLP mannosylation was specific for cross-presentation, as no influence on MHC II-restricted presentation was observed. Additionally, we showed that vaccination of mice with mannosylated SLPs containing epitopes from either ovalbumin or HPV E7 resulted in enhanced proliferation and activation of antigen-specific CD8+ T cells. These findings demonstrate that mannosylation of SLPs augments the induction of a cytotoxic T cell response in vitro and in vivo and might be a promising approach to induce cytotoxic T cell responses in e.g. cancer therapy and anti-viral immunity. |
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