Effects of immunogenic HER2 on the differentiation of T-cell in mouse

NING Hongyu; JIANG Tao; ZHANG Rui; HE Yu; YAO Wenbing; TIAN Hong

doi:10.11665/j.issn.1000-5048.20180115

Journal of China Pharmaceutical University > 2018 > 49(1): 102-108. > DOI: 10.11665/j.issn.1000-5048.20180115

NING Hongyu, JIANG Tao, ZHANG Rui, HE Yu, YAO Wenbing, TIAN Hong. Effects of immunogenic HER2 on the differentiation of T-cell in mouse[J]. Journal of China Pharmaceutical University, 2018, 49(1): 102-108. DOI: 10.11665/j.issn.1000-5048.20180115

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Effects of immunogenic HER2 on the differentiation of T-cell in mouse

NING Hongyu^1,2,
JIANG Tao^1,2,
ZHANG Rui^1,2,
HE Yu^1,2,
YAO Wenbing^1,2,
TIAN Hong^1,2

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Abstract

Abstract

In order to investigate the effects of p-nitrophenylalanine on the differentiation of T lymphocyte, human epidermal growth factor receptor 2(HER2)mutants were constructed by incorporating p-nitrophenylalanine to the extracellular domain of HER2. Mice were immunized with HER2 mutant to analyze the effects of p-nitrophenylalanine on the differentiation of T cell subsets. The results showed that the immunogenicity of HER2 protein was significantly enhanced by incorporation of immunogenic amino acids. HER2 mutants induced production of more anti-WT-HER2 antibody and greater titer of antibody than PBS and wild-type HER2 in the fifth week. The differentiation frequency of Th1 and Th2 cells showed no significant difference, but the differentiation frequency of Tfh cell was found to increase from 4% to 8%, while the differentiation frequency of Treg cell was found to decrease from 5% to 1% through flowcytometry analysis. The gene expression of Bcl-6 and FOXP3 were determined by quantitative real-time PCR. The results showed that the expression of Bcl-6 mRNA increased about 2 fold, while the expression of FOXP3 mRNA could be decreased to about 50% in HER2 mutant-immunized group. The secretion level of IL-21 in serum was also detected to increase from 4 to 28 pg/mL in HER2 mutant-immunized group. The above results confirm that HER2 mutants containing p-nitrophenylalanine can cause an efficient immune response by activating Tfh cell differentiation.
- immunogenic amino acid,
- HER2,
- follicular helper T cell,
- regulatory T cell,
- cellular dfferentiation

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