Fab-arm exchange is a misnomer
نویسنده
چکیده
There is increasing research activity aimed at understanding the molecular mechanisms underlying the phenomenon of so-called Fab-arm exchange, which has important implications for immunotherapies involving the anti-inflammatory IgG4 antibodies, and might also be relevant to our understanding of the etiology of the newly-described IgG4-related disease. I would like to point out that “Fab”-arm exchange is a misnomer and is misleading. It implies that only the Fab portion of the antibody is being exchanged; in fact, this dynamic process involves also the exchange of the Fc segment. The assumption underlying the coinage of Fab-arm exchange, I presume, was that the Fc portion of the IgG4 antibodies is identical and therefore, functionally, only Fab-arm exchange is a misnomer
منابع مشابه
Fab-arm exchange
636 mAbs Volume 4 issue 6 Immunology and structural biology are highly complex fields of study in which mechanisms and inter-relationships are often not easily understood. It is therefore quite common to use metaphors to make knowledge gained accessible to experts and non-experts alike. Thus we, for example, all know the antibody as a Y-shaped protein with two arms and a tail and we understand ...
متن کاملComparison of the ability of wild type and stabilized human IgG(4) to undergo Fab arm exchange with endogenous IgG(4)in vitro and in vivo.
Fab arm exchange by a stabilized anti-IL-31 IgG(4)S228P monoclonal antibody (mAb) was studied using physiologically relevant antibody concentrations and thiol exchange conditions, and directly compared to that of matched wild type IgG(4) (IgG(4)wt) and IgG(1) control antibodies. In vitro arm exchange between the test mAbs and a purified IgG(4)wt exchange partner was monitored using capillary is...
متن کاملAnti-inflammatory activity of human IgG4 antibodies by dynamic Fab arm exchange.
Antibodies play a central role in immunity by forming an interface with the innate immune system and, typically, mediate proinflammatory activity. We describe a novel posttranslational modification that leads to anti-inflammatory activity of antibodies of immunoglobulin G, isotype 4 (IgG4). IgG4 antibodies are dynamic molecules that exchange Fab arms by swapping a heavy chain and attached light...
متن کاملImpact of molecular processing in the hinge region of therapeutic IgG4 antibodies on disposition profiles in cynomolgus monkeys.
The IgG4 isotype antibody is a potential candidate for immunotherapy when reduced effector functions are desirable. However, antigen binding fragment (Fab) arm exchange leads to functional monovalency with potentially reduced therapeutic efficacy. Mutagenesis studies suggested that the CH3 domain and not the core hinge is dominantly involved in in vivo molecular processing. This work investigat...
متن کاملMechanism of immunoglobulin G4 Fab-arm exchange.
Immunoglobulin G (IgG) antibodies are symmetrical molecules that may be regarded as covalent dimers of 2 half-molecules, each consisting of a light chain and a heavy chain. Human IgG4 is an unusually dynamic antibody, with half-molecule exchange ("Fab-arm exchange") resulting in asymmetrical, bispecific antibodies with two different antigen binding sites, which contributes to its anti-inflammat...
متن کامل