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通过将人白细胞介素-1β的VQGEESNDK序列基因插入蛋白质抗原序列中来提高其免疫原性。

Increasing the immunogenicity of protein antigens through the genetic insertion of VQGEESNDK sequence of human IL-1 beta into their sequence.

作者信息

Beckers W, Villa L, Gonfloni S, Castagnoli L, Newton S M, Cesareni G, Ghiara P

机构信息

Immunobiological Research Institute, Siena, Italy.

出版信息

J Immunol. 1993 Aug 15;151(4):1757-64.

PMID:8345181
Abstract

The immunogenicity of two recombinant protein Ag containing the immunostimulatory sequence of human IL-1 beta 163-171 (VQGEESNDK) genetically engineered into their structure has been evaluated. The IL-1 beta sequence was inserted into the loop between alpha helices D and E of recombinant human ferritin H chain and into the hypervariable region of recombinant flagellin from Salmonella muenchen. The chimeric proteins were injected into mice and the level of humoral immune response developed against the native proteins was assessed by measuring the number of Ag-specific plaque forming cells/spleen or as the level of serum IgG response. The response was compared to that of mice receiving injections with wild-type protein Ag not containing the VQGEESNDK sequence or with hybrid constructs containing unrelated foreign peptide sequences of the same length. A significantly higher immune response was observed in mice immunized with chimeric constructs containing the human IL-1 beta 163-171 sequence. These data suggest that the insertion of the VQGEESNDK sequence may prove useful to increase the immune response against poorly immunogenic recombinant proteins.

摘要

对两种重组蛋白抗原的免疫原性进行了评估,这两种重组蛋白抗原在其结构中通过基因工程包含了人白细胞介素-1β 163-171(VQGEESNDK)的免疫刺激序列。白细胞介素-1β序列被插入到重组人铁蛋白H链的α螺旋D和E之间的环中,以及被插入到来自慕尼黑沙门氏菌的重组鞭毛蛋白的高变区中。将嵌合蛋白注射到小鼠体内,并通过测量抗原特异性噬斑形成细胞/脾脏的数量或作为血清IgG反应水平来评估针对天然蛋白产生的体液免疫反应水平。将该反应与接受不含VQGEESNDK序列的野生型蛋白抗原注射的小鼠或接受含有相同长度无关外源肽序列的杂交构建体注射的小鼠的反应进行比较。在用含有人类白细胞介素-1β 163-171序列的嵌合构建体免疫的小鼠中观察到显著更高的免疫反应。这些数据表明,插入VQGEESNDK序列可能被证明有助于增强针对免疫原性较差的重组蛋白的免疫反应。

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