Immune Response in HLA-A*02:01 Transgenic Humanized Mice to the Introduction of Horse IgG Antigen

V. Karkischenko, A. G. Berzina, I. A. Pomytkin, E. S. Glotova, M. A. Savina, D. V. Petrov, L. A. Taboyakova, L. A. Bolotskih, I. A. Vasil’eva
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Abstract

The introduction of a transgene can impact negatively the functioning of vital systems in biomodels. We  carried out a comparative analysis of the immune response of mice of the HLA-A*02:01 humanized transgenic line, mice with mouse β2-microglobulin gene knockout, and wild-type mice to the introduction of horse immunoglobulin as an antigen. The biomodel lines were created at the Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia. The maximum immune response was achieved on the 30th day from the onset of immunization in animals of the HLA-A*02:01 line and wild-type mice. Antibody titers in these groups increased sharply and approached 1:8,000,000 and 1:4,000,000, respectively. This indicates that genome modification in HLA-A*02:01 transgenic humanized mice did not affect functioning of the immune system. No similar dynamics of the increase in antibody titers was observed in the mice line with mouse β2-microglobulin gene knockout. On the 7th and 30th day, the antibody titer in this group increased to a value of 1:400 and 1:6,400, respectively. The weak immune response in mice with mouse β2-microglobulin gene knockout confirms the undeniably important role of  this protein in immune response formation.
HLA-A*02:01 转基因人源化小鼠对引入马 IgG 抗原的免疫反应
转基因的引入会对生物模型中重要系统的功能产生负面影响。我们对 HLA-A*02:01 人源化转基因品系小鼠、β2-微球蛋白基因敲除小鼠和野生型小鼠对引入马免疫球蛋白作为抗原的免疫反应进行了比较分析。这些生物模型系由俄罗斯联邦医学和生物局生物医学技术科学中心创建。HLA-A*02:01品系和野生型小鼠在免疫开始后的第30天达到最大免疫反应。这些组别的抗体滴度急剧上升,分别接近 1:8,000,000 和 1:4,000,000。这表明,HLA-A*02:01 转基因人源化小鼠的基因组改造并没有影响免疫系统的功能。在小鼠β2-微球蛋白基因敲除的小鼠品系中,没有观察到类似的抗体滴度上升动态。在第 7 天和第 30 天,该组小鼠的抗体滴度分别增至 1:400 和 1:6,400。小鼠β2-微球蛋白基因敲除小鼠的免疫反应较弱,这证实了该蛋白在免疫反应形成过程中的重要作用。
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