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

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.

1. Karkischenko V.N., Bolotskih L.A., Kapanadze G.D., Karkischenko N.N., Koloskova E.M., Maksimenko S.V., Matveyenko E.L., Petrova N.V., Ryabyh V.P., Revyakin A.O., Stankova N.V., Semenov H.H. Sozdanie linij transgennyh zhivotnyh-modelej s genami cheloveka NAT1 i NAT2 [Creation of lines of transgenic animal models with human NAT1 and NAT2 genes]. Biomedicina [Journal Biomed]. 2016;1:74–84. (In Russian).

2. Karkischenko V.N., Ryabyh V.P., Bolotskih L.A., Semenov H.H., Kapanadze G.D., Petrova N.V., Ezerskij V.A., Zhukova O.B., Koloskova E.M., Maksimenko S.V., Stolyarova V.N., Trubicina T.P. Fiziologo-embriologicheskie aspekty sozdaniya transgennyh myshej s integrirovannymi genami NAT1 i NAT2 cheloveka [Physiological and Embryological Aspects of Creation of Transgenic Mice with Integrated Human NAT1 and NAT2 Genes]. Biomedicina [Journal Biomed]. 2016;1:52–65. (In Russian).

3. Karkischenko N.N., Lazarev V.N., Manuvera V.A., Bobrovsky P.A., Petrova N.V., Koloskova E.M., Glotova E.S. Principy sozdaniya genno-inzhenernoj konstrukcii dlya polucheniya gumanizirovannyh transgennyh myshej, nesushchih gen HLA-С*07:02:01:01, kak proobraz innovacionnyh transgenno-nokautnyh biomodelej [Principles of Creation of a Genetic Engineering Construction for Obtaining Humanized Transgenic Mice with HLA-C*07:02:01:01, as a Promote of Innovative Transgenic and Knockout Biomodels]. Biomedicina [Journal Biomed]. 2024;20(1):8–20. (In Russian).

4. Savchenko E.S., Ogneva N.S., Karkischenko N.N. Embriologicheskie aspekty sozdaniya novoj gumanizirovannoj transgennoj linii myshej s integrirovannym genom cheloveka HLA-A*02:01:01:01 [Embryological Aspects of Creation a New Humanized Transgenic Mice with Integrated human HLA-A*02:01:01:01 gene]. Biomedicina [ Journal Biomed]. 2022;18(4):10–23. (In Russian).

5. Chuprin J., Buettner H., Seedhom M.O., et al. Humanized mouse models for immuno-oncology research. Nat. Rev. Clin. Oncol. 2023;20(3):192–206. DOI: 10.1038/s41571-022-00721-2.

6. Flisikowska T., Egli J., Flisikowski K., et al. A humanized minipig model for the toxicological testing of therapeutic recombinant antibodies. Nat. Biomed. Eng. 2022;6(11):1248–1256. DOI: 10.1038/s41551-022-00921-2.

7. Scardino A., Correale P., Firat H., et al. In vivo study of the GC90/IRIV vaccine for immune response and autoimmunity into a novel humanised transgenic mouse. Br. J. Cancer. 2003;89(1):199–205. DOI: 10.1038/sj.bjc.6601028.

8. Wright P.F. International standards for test methods and reference sera for diagnostic tests for antibody detection. Rev. Sci. Tech. 1998;17(2):527–549. DOI: 10.20506/rst.17.2.1118.