title: 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.
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.
authors.affiliation: Department of Research and Development, Institute of Virology, Vaccines and Sera-Torlak, Belgrade, Serbia. mstojanovic@torlakinstitut.com
authors.forename: Marijana
authors.initials: M
authors.lastname: Stojanović
authors.forename: Vladimir
authors.initials: V
authors.lastname: Petrušić
authors.forename: Irena
authors.initials: I
authors.lastname: Zivković
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Inić-Kanada
authors.forename: Ivana
authors.initials: I
authors.lastname: Stojićević
authors.forename: Emilija
authors.initials: E
authors.lastname: Marinković
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Dimitrijević
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology*; D002478:Cells, Cultured; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology*; D007114:Immunization; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018716:Molecular Mimicry; D018089:Superantigens / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology; D053482:beta 2-Glycoprotein I / Q000276:immunology*
chemical_list: D000906:Antibodies; D001324:Autoantigens; D000939:Epitopes; D018089:Superantigens; D013745:Tetanus Toxoid; D051193:Toll-Like Receptors; D053482:beta 2-Glycoprotein I