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首页> 外文期刊>The FASEB Journal >A novel peptide carrier for efficient targeting of antigens and nucleic acids to dendritic cells
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A novel peptide carrier for efficient targeting of antigens and nucleic acids to dendritic cells

机译：一种新型肽载体，用于有效靶向抗原和核酸对树突细胞

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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.—Sioud, M., Skorstad, G., Mobergslien, A., S?b?e-Larssen, S. A novel peptide carrier for efficient targeting of antigens and nucleic acids to dendritic cells.
机译：树突细胞（DCS）通过将捕获的抗原呈递至幼稚T细胞来引发宿主免疫反应。因此，DC结合肽可用于抗原靶向以促进幼稚和记忆免疫应答。通过对人单核细胞衍生DC的生物肽肽噬菌体文库，我们鉴定了新型DC结合肽。通过相应的合成肽抑制了具有高亲和力的NW肽（NWYLPWLGTNDW），结合DC的选定噬菌体之一，并通过相应的合成肽抑制其结合。抗原肽或与NW肽结合的NW肽结合的抗原肽或蛋白质内化，没有对DC表型和功能的负面影响。通过NW肽在HLA-A2 + / CMV +供体中的NW肽靶向CMV-PP65肽的DCs靶向DC，与未确定的肽相比（P <0.001）增加。刺激CMV的CD45RO耗尽外周血单核细胞吗？具有NW-PP65融合肽的供体膨胀PP65特异性前体T细胞。此外，NW肽介导的小干扰RNA递送至DC，并获得了显着的基因沉默。集体，数据显示，蛋白质和核酸可以通过NW肽引导至DC，使得能够有效吸收和功能效果，例如MHC I类和II分子的背景下的T细胞活化。-Sioud，M.，Skorstad ，G.，Mobergslien，A.，S？B？E-Larssen，S。一种新型肽载体，用于有效地靶向抗原和核酸对树突细胞。

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