title: A novel peptide carrier for efficient targeting of antigens and nucleic acids to dendritic cells.
abstract: Dendritic cells (DCs) initiate host immune responses by presenting captured antigens to naive T cells. Hence, DC-binding peptides may be used for antigen targeting to boost naive and memory immune responses. By biopanning peptide phage libraries on human monocyte-derived DCs, we identified novel DC-binding peptides. One of the selected phages, displaying the NW peptide (NWYLPWLGTNDW), bound DCs with high affinity, and its binding was inhibited by the corresponding synthetic peptide. Antigenic peptides or proteins conjugated to the NW peptide bound to DCs and were internalized without negative effects on DC phenotype and function. Ex vivo targeted delivery of CMV-pp65 peptides to DCs via the NW peptide increased T-cell responses in HLA-A2(+)/CMV(+) donors compared to untargeted peptides (P<0.001). Stimulation of CD45RO-depleted peripheral blood mononuclear cells from CMV(-) donors with the NW-pp65 fusion peptides expanded pp65-specific precursor T cells. Moreover, the NW peptide mediated small interfering RNA delivery to DCs, and a significant gene silencing was obtained. Collectively, the data reveal that proteins and nucleic acids can be directed to DCs through the NW peptide, enabling effective uptake and functional effects such as T-cell activation in the context of MHC class I and II molecules.
authors.affiliation: Department of Immunology, Oslo University, Radium Hospital, Montebello, N-0310 Oslo, Norway. mosioud@medisin.uio.no
authors.forename: Mouldy
authors.initials: M
authors.lastname: Sioud
authors.forename: Gjertrud
authors.initials: G
authors.lastname: Skorstad
authors.forename: Anne
authors.initials: A
authors.lastname: Mobergslien
authors.forename: Stein
authors.initials: S
authors.lastname: Sæbøe-Larssen
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000276:immunology; D000941:Antigens / Q000276:immunology* / Q000378:metabolism; D001667:Binding, Competitive / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009696:Nucleic Acids / Q000276:immunology* / Q000378:metabolism; D009842:Oligopeptides / Q000276:immunology* / Q000378:metabolism; D010750:Phosphoproteins / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D034741:RNA, Small Interfering / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000276:immunology / Q000378:metabolism
chemical_list: D000941:Antigens; D002352:Carrier Proteins; D015789:HLA-A2 Antigen; D009696:Nucleic Acids; D009842:Oligopeptides; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa
keywords: cancer vaccines; cross presentation; phage display; siRNA