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Role of molecular mimicry and polyclonal cell activation in the induction of pathogenic β2-glycoprotein I–directed immune response in Balb/c mice upon hyperimmunization with tetanus toxoid

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Abstract

It is known that tetanus toxoid (TTd)-hyperimmunization induces increased titer of sera β2-glycoprotein I (β2GPI)-specific antibodies (Abs) in Balb/c mice. The concentrations of such induced anti-β2GPI Abs as well as their pathogenic potential are strongly influenced by the context of TTd application. β2GPI-specific immune response is established as a part of TTd-specific immune response by molecular mimicry mechanism due to structural homology between TTd and β2GPI. This finding is supported by the following facts: (1) cross-reactive Abs that recognize both TTd and β2GPI epitopes are present in Balb/c mice sera; (2) anti-TTd Abs secretion in splenic cultures is induced after β2GPI stimulation and vice versa. However, analyses of (1) IL-10 production following in vitro stimulation of immunized Balb/c mice splenocytes by TTd, β2GPI or glutaraldehyde-treated β2GPI and (2) specific impact of ConA and agonists of TLR2, TLR4, and TLR9 on anti-TTd and autoreactive Abs secretion strongly imply that these two branches of the TTd-induced immune response do not use identical cell populations and are regulated in a different way. Results presented in this paper describe that structural homology between foreign and self-antigens could focus mounted autoreactive immune response toward specific self-structure, but the context of antigen application, including a history of previous immune stimulations and adjuvants applied together with the antigen, are the main factors which determine the outcome of the induced immune response.

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Acknowledgments

This work was supported by 172049 grant from the Ministry of Science, Republic of Serbia.

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  1. Aleksandra Inić-Kanada

    Present address: Laura Bassi Centres of Expertise, OCUVAC—Centre of Ocular Inflammation and Infection, Institute of Specific Prophylaxis and Tropical Medicine, Centre for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Kinderspitalgasse 15, 1090, Vienna, Austria

Authors and Affiliations

  1. Department of Research and Development, Institute of Virology, Vaccines and Sera—Torlak, Vojvode Stepe 458, 11152, Belgrade, Serbia

    Marijana Stojanović, Vladimir Petrušić, Irena Živković, Aleksandra Inić-Kanada, Ivana Stojićević, Emilija Marinković & Ljiljana Dimitrijević

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  1. Marijana Stojanović
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Correspondence to Marijana Stojanović.

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Stojanović, M., Petrušić, V., Živković, I. et al. Role of molecular mimicry and polyclonal cell activation in the induction of pathogenic β2-glycoprotein I–directed immune response in Balb/c mice upon hyperimmunization with tetanus toxoid. Immunol Res 56, 20–31 (2013). https://doi.org/10.1007/s12026-012-8343-1

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