Hoang Vinh Van, Zou Yanshuang, Kurata Kentaro, Enomoto Keiichi
School of Environmental Science and Engineering, Kochi University of Technology, Kochi, Japan.
School of Environmental Science and Engineering, Kochi University of Technology, Kochi, Japan.
Protein Expr Purif. 2015 May;109:62-9. doi: 10.1016/j.pep.2015.02.001. Epub 2015 Feb 7.
Peptides containing T-cell epitopes from allergens, which are not reactive to allergen-specific IgE, are appropriate candidates as antigens for specific immunotherapy against allergies. To develop a vaccine that can be used in practical application to prevent and treat Japanese cedar pollen allergy, four major T-cell epitopes from the Cry j 1 antigen and six from the Cry j 2 antigen were selected to design cry j 1 epi and cry j 2 epi, DNA constructs encoding artificial polypeptides of the selected epitopes. To apply cholera toxin B subunit (CTB) as an adjuvant, cry j 1 epi and cry j 2 epi were linked and then fused to the CTB gene in tandem to construct a fusion gene, ctb-linker-cry j 1 epi- cry j 2 epi-flag. The fusion gene was introduced into a pET-28a(+) vector and expressed in Escherichia coli BL21(DE3). The expressed recombinant protein was purified by a His-tag affinity column and confirmed by western blot analysis using anti-CTB and anti-FLAG antibodies. The purified recombinant protein also proved to be antigenic against anti-Cry j 1 and anti-Cry j 2 antibodies. Expression of the recombinant protein induced with 1mM IPTG reached a maximum in 3-5h, and recovery of the affinity-purified recombinant protein was approximately 120mg/L of culture medium. The present study indicates that production of sufficient amounts of recombinant protein with antigenic epitopes may be possible by recombinant techniques using E. coli or other bacterial strains for protein expression.
含有来自变应原的T细胞表位且对变应原特异性IgE无反应性的肽,是特异性免疫治疗变应性疾病的合适抗原候选物。为了开发一种可实际用于预防和治疗日本雪松花粉过敏的疫苗,从Cry j 1抗原中选择了四个主要T细胞表位,从Cry j 2抗原中选择了六个,以设计cry j 1 epi和cry j 2 epi,即编码所选表位人工多肽的DNA构建体。为了应用霍乱毒素B亚基(CTB)作为佐剂,将cry j 1 epi和cry j 2 epi连接起来,然后串联融合到CTB基因上,构建融合基因ctb-linker-cry j 1 epi-cry j 2 epi-flag。将融合基因导入pET-28a(+)载体并在大肠杆菌BL21(DE3)中表达。表达的重组蛋白通过His标签亲和柱纯化,并用抗CTB和抗FLAG抗体进行蛋白质印迹分析进行确认。纯化的重组蛋白也被证明对抗Cry j 1和抗Cry j 2抗体具有抗原性。用1mM IPTG诱导的重组蛋白表达在3-5小时达到最大值,亲和纯化的重组蛋白回收率约为120mg/L培养基。本研究表明,通过使用大肠杆菌或其他细菌菌株进行蛋白质表达的重组技术,有可能产生足够量的具有抗原表位的重组蛋白。