Efficient cross-presentation of soluble exogenous antigens introduced into dendritic cells using a weak-based amphiphilic peptide
Efficient cross-presentation of soluble exogenous antigens introduced into dendritic cells using a weak-based amphiphilic peptide
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DOI：
10.1016/j.bbrc.2010.01.019
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发表时间：
2010-02-05
影响因子：
3.1
通讯作者：
Kakimi, Kazuhiro
中科院分区：
文献类型：
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作者：
Ikeuchi, Nobuhito;Futami, Junichiro;Kakimi, Kazuhiro
为了开发一种基于树突状细胞(DC)的疫苗，通过交叉提呈诱导抗原特异性CD8(+)T细胞反应，我们测试了一种新的抗原递送系统，该系统通过内吞介导的机制将可溶性抗原引入细胞胞浆，避免破坏质膜(“Endo-Porter”(TM))。从内体释放到细胞质的蛋白质被蛋白酶体降解，碎裂的抗原肽被呈递到经典的胞浆MHC I类途径。在Endo-Porter存在的情况下，OVA蛋白冲击的DC有效地刺激OVA多肽特异性CD8(+)T(OT-I)细胞。虽然该药将一些内吞的抗原从经典的MHC II类限制性递送途径转移到I类途径，但发现CD4(+)T细胞的激活不受Endo-Porter介导的抗原递送的阻碍。相反，它是相当增强的，可能是由于抗原摄取的增加。由于需要特定的CD4(+)T细胞帮助才能许可DC进行交叉激发，因此Endo-Porter介导的抗原递送是开发针对CD4(+)和CD8(+)T细胞的更有效的癌症疫苗的一种有前途的方法。(C)2010 Elsevier Inc.保留所有权利。
To develop a novel dendritic cell (DC)-based vaccine for inducing antigen-specific CD8(+) T cell responses by cross-presentation, we tested a novel antigen delivery system that introduces Soluble antigens into the cytosol of cells by an endocytosis-mediated mechanism which avoids damaging the plasma membrane ("Endo-Porter"(TM)). Proteins released from endosomes into the cytoplasm are degraded by the proteasome, and fragmented antigenic peptides are presented to the classical cytosolic MHC class I pathway. DCs pulsed with OVA protein in the presence of Endo-Porter efficiently stimulate OVA peptide-specific CD8(+) T (OT-I) cells. Although this agent diverts some of the endocytosed antigens away from the classical MHC class II-restricted presentation pathway to the class I pathway, the activation of CD4(+) T cells was found not to be hampered by Endo-Porter-mediated antigen delivery. On the contrary, it was rather augmented, probably due to the increased uptake of antigen. Because specific CD4(+) T cell help is required to license DCs for cross-priming, Endo-Porter-mediated antigen delivery is a promising approach for developing more efficient cancer vaccines targeting both CD4(+) and CD8(+) T cells. (C) 2010 Elsevier Inc. All rights reserved.