Binding of LcrV protein from Yersinia pestis to human T-cells induces apoptosis, which is completely blocked by specific antibodies

Vyacheslav M. Abramov, Igor V. Kosarev, Vladimir Motin, Valentin S. Khlebnikov, Raisa N. Vasilenko, Vadim K. Sakulin, Andrey V. Machulin, Vladimir N. Uversky, Andrey V. Karlyshev

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1 Scopus citations

Abstract

The V antigen (LcrV) of the plague bacterium Yersinia pestis is a potent protective protein that is considered as a vaccine component for humans. LcrV mediates the delivery of Yop toxins into host cells and upregulates TLR2-dependent IL-10 production. Although LcrV can interact with the receptor-bound human interferon-γ (hIFN-γ), the significance of these interactions in plague pathogenesis is not known. In this study, we determined the parameters of specific interactions of LcrV and LcrV68–326 with primary human thymocytes and Jurkat T-leukemia cells in the presence of receptor-bound hIFN-γ. Although the C-terminal region of hIFN-γ contains a GRRA138–141 site needed for high-affinity binding of LcrV and LcrV68–326, in the hIFN-γ homodimer, these GRRA138–141 target sites becomes accessible for targeting by LcrV or LcrV68–326 only after immobilization of the hIFN-γ homodimer on the hIFN-γ receptors of thymocytes or Jurkat T-cells. The interaction of LcrV or LcrV68–326 with receptor-bound hIFN-γ on the thymocytes or Jurkat T-cells caused apoptosis of both cell types, which can be completely blocked by the addition of monoclonal antibodies specific to the LEEL32–35 and DEEI203–206 sites of LcrV. The ability of LcrV to utilize hIFN-γ is insidious and may account in part for the severe symptoms of plague in humans.

Keywords

  • Apoptosis
  • Interferon-γ
  • LcrV protein
  • Plague
  • Yersinia

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

Cite this

Abramov, V. M., Kosarev, I. V., Motin, V., Khlebnikov, V. S., Vasilenko, R. N., Sakulin, V. K., Machulin, A. V., Uversky, V. N., & Karlyshev, A. V. (Accepted/In press). Binding of LcrV protein from Yersinia pestis to human T-cells induces apoptosis, which is completely blocked by specific antibodies. International Journal of Biological Macromolecules. https://doi.org/10.1016/j.ijbiomac.2018.09.054