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

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 LcrV 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 GRRA site needed for high-affinity binding of LcrV and LcrV, in the hIFN-γ homodimer, these GRRA target sites becomes accessible for targeting by LcrV or LcrV only after immobilization of the hIFN-γ homodimer on the hIFN-γ receptors of thymocytes or Jurkat T-cells. The interaction of LcrV or LcrV 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 LEEL and DEEI 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.

Infection-Associated Thymic Atrophy

“…In addition, LPS is not involved in thymic atrophy induced by Y. enterocolitica ( 79 ). The V antigen of Yersinia pestis can interact with receptor-bound human IFN-γ located in thymocytes, triggering thymocyte apoptosis in vitro ( 80 ). Again, the specific mechanism here remains to be clarified.…”

Antibodies Inhibiting the Type III Secretion System of Gram-Negative Pathogenic Bacteria

“…One example of this phenomenon is seen by specific anti-LcrV Ab blocking the apoptotic action of LcrV, the Yersinia spp. needle tip, against human T-cells [36].…”