PMID- 23671272 OWN - NLM STAT- MEDLINE DCOM- 20131216 LR - 20130802 IS - 1530-6860 (Electronic) IS - 0892-6638 (Linking) VI - 27 IP - 8 DP - 2013 Aug TI - A novel peptide carrier for efficient targeting of antigens and nucleic acids to dendritic cells. PG - 3272-83 LID - 10.1096/fj.12-224758 [doi] AB - 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. FAU - Sioud, Mouldy AU - Sioud M AD - Department of Immunology, Oslo University, Radium Hospital, Montebello, N-0310 Oslo, Norway. mosioud@medisin.uio.no FAU - Skorstad, Gjertrud AU - Skorstad G FAU - Mobergslien, Anne AU - Mobergslien A FAU - Saeboe-Larssen, Stein AU - Saeboe-Larssen S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130513 PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - 0 (Antigens) RN - 0 (Carrier Proteins) RN - 0 (HLA-A2 Antigen) RN - 0 (Nucleic Acids) RN - 0 (Oligopeptides) RN - 0 (Phosphoproteins) RN - 0 (RNA, Small Interfering) RN - 0 (Viral Matrix Proteins) RN - 0 (cytomegalovirus matrix protein 65kDa) SB - IM MH - Amino Acid Sequence MH - Antigen Presentation/immunology MH - Antigens/*immunology/metabolism MH - Binding, Competitive/immunology MH - Carrier Proteins/immunology/metabolism MH - Cells, Cultured MH - Dendritic Cells/*immunology/metabolism MH - Flow Cytometry MH - HLA-A2 Antigen/immunology/metabolism MH - Humans MH - Leukocytes, Mononuclear/immunology/metabolism MH - Lymphocyte Activation/immunology MH - Microscopy, Fluorescence MH - Monocytes/immunology/metabolism MH - Nucleic Acids/*immunology/metabolism MH - Oligopeptides/*immunology/metabolism MH - Phosphoproteins/immunology/metabolism MH - Protein Binding/immunology MH - RNA, Small Interfering/genetics/immunology/metabolism MH - T-Lymphocytes/immunology/metabolism MH - Viral Matrix Proteins/immunology/metabolism OTO - NOTNLM OT - cancer vaccines OT - cross presentation OT - phage display OT - siRNA EDAT- 2013/05/15 06:00 MHDA- 2013/12/18 06:00 CRDT- 2013/05/15 06:00 PHST- 2013/05/15 06:00 [entrez] PHST- 2013/05/15 06:00 [pubmed] PHST- 2013/12/18 06:00 [medline] AID - fj.12-224758 [pii] AID - 10.1096/fj.12-224758 [doi] PST - ppublish SO - FASEB J. 2013 Aug;27(8):3272-83. doi: 10.1096/fj.12-224758. Epub 2013 May 13.