A DNA adjuvant encoding a fusion protein between anti-CD3 single-chain Fv and AIMP1 enhances T helper type 1 cell-mediated immune responses in antigen-sensitized mice

2009 
SummaryT helper type 1 (Th1) cell-mediated immune responses contribute to hostdefences against intracellular pathogen infections and cancer. Previously,we found that aminoacyl tRNA synthetase-interacting multifunctionalprotein 1 (AIMP1) activated macrophages and dendritic cells to enhanceTh1 responses. Herein, we manipulated this property to improve Th1immune responses in vivo by constructing a mammalian expression plas-mid (pAnti-CD3sFv/AIMP1) encoding AIMP1 fused to the anti-CD3single-chain Fv (sFv), the smallest unit of the antibody that interacts withthe CD3e region of the T-cell receptor. Intramuscular injection of ovalbu-min (OVA)-sensitized BALB/c mice with pAnti-CD3sFv/AIMP1 DNAadjuvant increased the OVA-specific, interferon-c production by theirCD4 + T cells and the levels of anti-OVA immunoglobulin G2a (IgG2a)isotype in their sera. Furthermore, the pAnti-CD3sFv/AIMP1 DNA adju-vant decreased interleukin-4 production and anti-OVA IgE levels in theOVA-injected mice. Importantly, the pAnti-CD3sFv/AIMP1 was more effi-cient than a mixture of pAnti-CD3sFv and pAIMP1 in inducing OVA-specific Th1 immune responses and also in inhibiting OVA-specific Th2responses during antigen priming. These studies indicated that the pAnti-CD3sFv/AIMP1 fusion DNA adjuvant enhanced Th1 immune responsesin antigen-sensitized mice.Keywords: aminoacyl t-RNA synthetase-interacting multifunctionalprotein 1; anti-CD3; DNA adjuvant; T cell; T helper cell response
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