Targeting the nuclear antigen I of Epstein-Barr virus to the human endocytic receptor DEC-205 stimulates protective T-cell responses
Targeting the nuclear antigen I of Epstein-Barr virus to the human endocytic receptor DEC-205 stimulates protective T-cell responses
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DOI：
10.1182/blood-2008-03-148072
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发表时间：
2008-08-15
期刊：
影响因子：
20.3
通讯作者：
Munz, Christian
中科院分区：
文献类型：
--
作者：
Gurer, Cagan;Strowig, Till;Munz, Christian
树突状细胞（DCs）表达多种内吞受体，所述内吞受体将主要组织相容性（MHC）I类和II类抗原分别呈递给CD 8（+）和CD 4（+）T细胞。在这里，我们表明，靶向EB病毒（EBV）核抗原1（EBNA 1），其中之一，人多凝集素DEC-205受体，在DC成熟刺激聚（I：C），扩增EBNA 1特异性的CD 4（+）和CD 8（+）记忆T细胞，这些淋巴细胞可以控制自体EBV感染的B细胞在体外的生长。此外，使用具有重建的人免疫系统组分的新型小鼠模型，我们证明了用α DEC-205-EBNA 1抗体接种引发EBNA 1特异性IFN-γ分泌T细胞，并且还在免疫小鼠的亚组中诱导抗EBNA 1抗体。由于EBNA 1是一种在所有被这种病毒感染的增殖细胞中表达的EBV抗原，我们的数据表明，DEC-205靶向应该被探索作为针对症状性原发性EBV感染和针对EBV相关恶性肿瘤的疫苗接种方法。
Dendritic cells (DCs) express many endocytic receptors that deliver antigens for major histocompatibility class (MHC) I and II presentation to CD8(+) and CD4(+) T cells, respectively. Here, we show that targeting Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) to one of them, the human multilectin DEC-205 receptor, in the presence of the DC maturation stimulus poly(I:C), expanded EBNA1-specific CD4(+) and CD8(+) memory T cells,and these lymphocytes could control the outgrowth of autologous EBV-infected B cells in vitro. In addition, using a novel mouse model with reconstituted human immune system components, we demonstrated that vaccination with alpha DEC-205-EBNA1 antibodies primed EBNA1-specific IFN-gamma-secreting T cells and also induced anti-EBNA1 antibodies in a subset of immunized mice. Because EBNA1 is the one EBV antigen that is expressed in all proliferating cells infected with this virus, our data suggest that DEC-205 targeting should be explored as a vaccination approach against symptomatic primary EBV infection and against EBV-associated malignancies.