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991.
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Human CD8+ T cells transduced with an additional receptor bispecific for both Mycobacterium tuberculosis and HIV‐1 recognize both epitopes 下载免费PDF全文
Chao‐Ying Zhou Qian Wen Xiao‐Jie Chen Rui‐Ning Wang Wen‐Ting He Shi‐Meng Zhang Xia‐Lin Du Li Ma 《Journal of cellular and molecular medicine》2016,20(10):1984-1998
Tuberculosis (TB) and human immunodeficiency virus type 1 (HIV‐1) infection are closely intertwined, with one‐quarter of TB/HIV coinfected deaths among people died of TB. Effector CD8+ T cells play a crucial role in the control of Mycobacterium tuberculosis (MTB) and HIV‐1 infection in coinfected patients. Adoptive transfer of a multitude of effector CD8+ T cells is an appealing strategy to impose improved anti‐MTB/HIV‐1 activity onto coinfected individuals. Due to extensive existence of heterologous immunity, that is, T cells cross‐reactive with peptides encoded by related or even very dissimilar pathogens, it is reasonable to find a single T cell receptor (TCR) recognizing both MTB and HIV‐1 antigenic peptides. In this study, a single TCR specific for both MTB Ag85B199‐207 peptide and HIV‐1 Env120‐128 peptide was screened out from peripheral blood mononuclear cells of a HLA‐A*0201+ healthy individual using complementarity determining region 3 spectratype analysis and transferred to primary CD8+ T cells using a recombinant retroviral vector. The bispecificity of the TCR gene‐modified CD8+ T cells was demonstrated by elevated secretion of interferon‐γ, tumour necrosis factor‐α, granzyme B and specific cytolytic activity after antigen presentation of either Ag85B199‐207 or Env120‐128 by autologous dendritic cells. To the best of our knowledge, this study is the first report proposing to produce responses against two dissimilar antigenic peptides of MTB and HIV‐1 simultaneously by transfecting CD8+ T cells with a single TCR. Taken together, T cells transduced with the additional bispecific TCR might be a useful strategy in immunotherapy for MTB/HIV‐1 coinfected individuals. 相似文献
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IDENTIFICATION AND MOLECULAR CHARACTERIZATION OF TWO SERINE PROTEASES AND THEIR POTENTIAL INVOLVEMENT IN PROPHENOLOXIDASE ACTIVATION IN Plutella xylostella 下载免费PDF全文
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Junwei Li Shaoying Xiao Xiaoxiao Xie Hui Zhou Chunli Pang Shanshan Li Hailin Zhang Diomedes E. Logothetis Yong Zhan Hailong An 《Proteins》2016,84(12):1929-1937
Kir2.1 (also known as IRK1) plays key roles in regulation of resting membrane potential and cell excitability. To achieve its physiological roles, Kir2.1 performs a series of conformational transition, named as gating. However, the structural basis of gating is still obscure. Here, we combined site‐directed mutation, two‐electrode voltage clamp with molecular dynamics simulations and determined that H221 regulates the gating process of Kir2.1 by involving a weak interaction network. Our data show that the H221R mutant accelerates the rundown kinetics and decelerates the reactivation kinetics of Kir2.1. Compared with the WT channel, the H221R mutation strengthens the interaction between the CD‐ and G‐loops (E303‐R221) which stabilizes the close state of the G‐loop gate and weakens the interactions between C‐linker and CD‐loop (R221‐R189) and the adjacent G‐loops (E303‐R312) which destabilizes the open state of G‐loop gate. Our data indicate that the three pairs of interactions (E303‐H221, H221‐R189 and E303‐R312) precisely regulate the G‐loop gate by controlling the conformation of G‐loop. Proteins 2016; 84:1929–1937. © 2016 Wiley Periodicals, Inc. 相似文献
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Yakun Hu Libing Deng Jie Zhang Xin Fang Puming Mei Xuebing Cao Jiari Lin Yi Wei Xiong Zhang Renshi Xu 《Molecular neurobiology》2016,53(7):4302-4318
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