Fab-arm exchange
نویسندگان
چکیده
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 the specificity of antibodyantigen binding as a key-into-lock interaction. Are these metaphors strictly correct? No, of course not. Nevertheless, they are well-recognized and serve to provide some immediate and general understanding of key features. When faced with the challenge of designing a simple descriptor or metaphor for the process leading to the exchange of human IgG4 “half-molecules,” we discussed various options with experts in the field and came up with the term “Fab-arm exchange.” The phrase is simply meant to highlight the functional consequence of this mechanism, i.e., the exchange of antigen-binding parts between parental antibody molecules leading to novel binding combinations in the product. Professor Pandey argues in his letter that Fab-arm exchange is a misnomer and should be changed to IgG4-arm exchange with the argument that allotypic differences are ignored. Apart from the fact that, seen from Pandey’s view, the phrase IgG4-arm exchange suffers from similar weaknesses as the original (and should be termed IgG4-arm-and-tail exchange instead), clearly we disagree. This is not Fab-arm exchange What’s in a name?
منابع مشابه
Fab-arm exchange is a misnomer
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 ex...
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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...
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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...
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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...
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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...
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عنوان ژورنال:
دوره 4 شماره
صفحات -
تاریخ انتشار 2012