Paradoxical behavior of asymmetric IgG antibodies

Abstract

Changes in the quantity and quality of antibodies occur in the course of an immune response. This review describes the physicochemical and biological properties of asymmetric antibodies as well as their functions, beneficial or harmful to the host, according to the nature of the antigen and the particular situation in which they act. Asymmetric antibodies have two paratopes, one of high affinity, with K0 similar to that of symmetric antibodies, and the other one with an affinity for the antigen 100 times lower. Functional univalence is due to steric hindrance present in one of the paratopes by the carbohydrate moiety attached to the Fd fragment of the Fab region, so these antibodies are unable to form large antibody-antigen complexes and cannot trigger reactions, such as complement fixation, phagocytic activity and antigen clearance. When asymmetric IgG antibodies are specific for self-antigens, they prove beneficial for the host by exerting regulatory functions. In allergic manifestations, in autoimmune diseases and especially during pregnancy, despite the fact that the antigens responsible for the process are foreign to the host, they also perform beneficial activity. During pregnancy, the placenta secretes molecules or factors that regulate the synthesis of these antibodies, thus favoring fetal protection.

Intercellular Adhesion Molecule-1/LFA-1 Cross Talk Is a Proximate Mediator Capable of Disrupting Immune Integration and Tolerance Mechanism at the Feto-Maternal Interface in Murine Pregnancies

“…These AAbs are unable to activate effector mechanisms of the immune response. However, AAbs may block effector cell targets, e.g., paternal Ags expressed by the placenta (12,49). We hypothesize that the ICAM-1/LFA-1-mediated Th1 Ͼ Th2 skew results in a decreased AAb synthesis by B cells.…”

“…Recently, it has been reported that Treg cells are required for the maternal immune system to tolerate the fetal allograft (9,10 An additional mechanism favoring the immunological symbiosis between mother and fetus is the production of AAbs (11)(12)(13). These AAbs are unable to activate effector mechanisms of the immune response.…”

“…Hence, it has been suggested that plural tolerance mechanisms have evolved to ensure the maintenance of the feto-placental graft. Such mechanisms include the following: 1) the predominance of anti-inflammatory, Th2 cytokines over proinflammatory Th1 cytokines in the decidua (3)(4)(5); 2) the decidual expression of indoleamine 2,3-dioxygenase (IDO), 3 an enzyme that famishes immune rejection by depriving the T cells of tryptophan and/or by inhibiting lymphocyte proliferation (6 -8); 3) the presence of CD4 ϩ CD25 bright regulatory T (Treg) cells, which suppress an aggressive allogeneic response directed against the fetus, as simultaneously described in human pregnancies by the Saito group (9) and in murine pregnancies (10); and 4) the synthesis of asymmetric IgG Abs (AAbs), which have been suggested to camouflage paternal Ags expressed by the placenta (11)(12)(13). In addition, it has become apparent in the past few years that dendritic cells (DCs) seem to be an essential regulatory cell subset at the feto-maternal interface in mediating tolerance (14 -16).…”

The Apparent Monovalency of Human IgG4 Is Due to Bispecificity

“…Margni and Borel [6]favor the second explanation. The proposed mechanism is asymmetrical glycosylation of one of the two antigen–binding regions.…”

Protective autoantibodies: Role in homeostasis, clinical importance, and therapeutic potential

“…Asymmetric IgG antibodies act in a competitive way when they are mixed with precipitating or symmetric antibodies of the same specificity, and the action of these antibodies 2600 SHOENFELD AND TOUBI therefore depends on their respective proportion in the mixture (20). The increased ratio of asymmetric to symmetric IgG in sera from older rats suggests that asymmetric antibodies may exert a beneficial effect by protecting self antigens from inducing severe immune responses (21).…”