Murine monoclonal antibody 26 raised against tetanus toxoid cross-reacts with beta2-glycoprotein I: its characteristics and role in molecular mimicry.
OBJECTIVE
Studies on experimental antiphospholipid syndrome (APS) models proved that molecular mimicry between plasma protein beta(2)-glycoprotein I (beta(2)GPI) and structure within micro-organisms or their products, might be a cause for experimental APS. Considering the heterogeneity of polyclonal antiphospholipid antibodies (aPLs), it is important to define the precise characteristics of pathogenic aPLs. To avoid the influence of polyclonality and to further analyse the connection between molecular mimicry and APS, we produced monoclonal antibodies (MAbs) against tetanus toxoid (TTd) and tested their reactivity against beta(2)GPI.


METHODS
In this report, we analysed the characteristics of MAb26 raised against TTd and cross-reactive with beta(2)GPI: its binding properties in various in vitro immunoassays, its specific interactions with surface epitopes expressed on apoptotic cells and its role in vivo.


RESULTS
We have demonstrated that MAb26: (i) binds beta(2)GPI being immobilized on an appropriate surface: irradiated polystyrene plates, non-irradiated plates pre-coated with anionic phospholipids and polyvinylidene fluoride membrane; (ii) binds specifically to apoptotic but not to viable cells and the binding is beta(2)GPI-dependent; and (iii) induces a pathologic pregnancy outcome when passively injected into BALB/c mice.


CONCLUSIONS
This study concluded that certain subpopulations of antibodies raised against TTd and cross-reactive with beta(2)GPI, because of the molecular mimicry mechanism, could have pathologic potential.
Inic-Kanada
Aleksandra
A
Institute of Virology, Vaccines and Sera - Torlak, Belgrade, Serbia. aleksandra612@gmail.com
Stojanovic
Marijana
M
Zivkovic
Irena
I
Kosec
Dusko
D
Micic
Mileva
M
Petrusic
Vladimir
V
Zivancevic-Simonovic
Snezana
S
Dimitrijevic
Ljiljana
L
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D017209:Apoptosis; D002478:Cells, Cultured; D003429:Cross Reactions / Q000276:immunology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D018716:Molecular Mimicry / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology*; D053482:beta 2-Glycoprotein I / Q000276:immunology*
D017152:Antibodies, Antiphospholipid; D000911:Antibodies, Monoclonal; D013745:Tetanus Toxoid; D053482:beta 2-Glycoprotein I