Division of Virology, Innsbruck Medical University, Innsbruck, Austria.
PLoS One. 2012;7(9):e45102. doi: 10.1371/journal.pone.0045102. Epub 2012 Sep 17.
Dendritic cells (DC) represent the most potent antigen presenting cells and induce efficient cytotoxic T lymphocyte (CTL) responses against viral infections. Targeting antigens (Ag) to receptors on DCs is a promising strategy to enhance antitumor and antiviral immune responses induced by DCs. Here, we investigated the potential of CD11c-specific single-chain fragments (scFv) fused to an immunodominant peptide of Friend retrovirus for induction of virus-specific T cell responses by DCs. In vitro CD11c-specific scFv selectively targeted viral antigens to DCs and thereby significantly improved the activation of virus-specific T cells. In vaccination experiments DCs loaded with viral Ag targeted to CD11c provided improved rejection of FV-derived tumors and efficiently primed virus-specific CTL responses after virus challenge. Since the induction of strong virus-specific T cell responses is critical in viral infections, CD11c targeted protein vaccines might provide means to enhance the cellular immune response to prophylactic or therapeutic levels.
树突状细胞(DC)是最有效的抗原呈递细胞,可诱导针对病毒感染的有效细胞毒性 T 淋巴细胞(CTL)反应。将抗原(Ag)靶向 DC 上的受体是增强 DC 诱导的抗肿瘤和抗病毒免疫反应的一种有前途的策略。在这里,我们研究了与 Friend 逆转录病毒的免疫优势肽融合的 CD11c 特异性单链片段(scFv)诱导 DC 产生病毒特异性 T 细胞反应的潜力。体外 CD11c 特异性 scFv 选择性地将病毒抗原靶向 DC,从而显著改善了病毒特异性 T 细胞的激活。在疫苗接种实验中,负载靶向 CD11c 的病毒 Ag 的 DC 提供了对 FV 衍生肿瘤的更好排斥,并在病毒攻击后有效地引发了病毒特异性 CTL 反应。由于诱导强烈的病毒特异性 T 细胞反应对于病毒感染至关重要,因此靶向 CD11c 的蛋白疫苗可能提供增强针对预防性或治疗性水平的细胞免疫反应的手段。