title: Enhanced cross-presentation and improved CD8+ T cell responses after mannosylation of synthetic long peptides in mice.
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.
authors.affiliation: Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Rauen
authors.affiliation: Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kreer
authors.affiliation: Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
authors.forename: Arlette
authors.initials: A
authors.lastname: Paillard
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Suzanne
authors.initials: S
authors.lastname: van Duikeren
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Willemien E
authors.initials: WE
authors.lastname: Benckhuijsen
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Marcel G
authors.initials: MG
authors.lastname: Camps
authors.affiliation: Department of Bio-organic Synthesis, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: A Rob P M
authors.initials: AR
authors.lastname: Valentijn
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Ferry
authors.initials: F
authors.lastname: Ossendorp
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Jan W
authors.initials: JW
authors.lastname: Drijfhout
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Ramon
authors.initials: R
authors.lastname: Arens
authors.affiliation: Life and Medical Sciences Institute, University of Bonn, Bonn, Germany; Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Sven
authors.initials: S
authors.lastname: Burgdorf
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology*; D000941:Antigens / Q000737:chemistry / Q000276:immunology*; D049109:Cell Proliferation; D002645:Chickens; D045142:Cross-Priming; D011992:Endosomes / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression; D007111:Immunity, Cellular / Q000187:drug effects*; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology; D008358:Mannose / Q000276:immunology* / Q000378:metabolism; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000737:chemistry / Q000276:immunology; D050725:Papillomavirus E7 Proteins / Q000737:chemistry / Q000276:immunology; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology*; D021381:Protein Transport; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology; D016415:Sequence Alignment; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D000941:Antigens; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D050725:Papillomavirus E7 Proteins; D010455:Peptides; D011956:Receptors, Cell Surface; C059731:oncogene protein E7, Human papillomavirus type 16; D010047:Ovalbumin; D008358:Mannose