Thefragment antigen-binding region (Fab region) is a region on anantibody that binds toantigens. It is composed of one constant and one variable domain of each of theheavy and thelight chain. The variable domain contains theparatope (the antigen-binding site), comprising a set ofcomplementarity-determining regions, at theamino terminal end of themonomer. Each arm of the Y thus binds anepitope on the antigen.
In an experimental setting,Fc and Fab fragments can be generated in the laboratory. Theenzymepapain can be used to cleave animmunoglobulin monomer into two Fab fragments and an Fc fragment. Conversely, the enzymepepsin cleaves below the hinge region, so the result instead is aF(ab')2 fragment and a pFc' fragment. Recently another enzyme for generation of F(ab')2 has been commercially available. The enzyme IdeS (Immunoglobulin degrading enzyme fromStreptococcus pyogenes, trade name FabRICATOR) cleavesIgG in a sequence specific manner at neutral pH. The F(ab')2 fragment can be split into twoFab' fragments by mildreduction.[1]
The variable regions of the heavy and light chains can be fused together to form asingle-chain variable fragment (scFv), which is only half the size of the Fab fragment, yet retains the original specificity of the parent immunoglobulin.[2]
Fabs have seen some therapeutic use inemergency medicine as an antidote. Marketed applications includedigoxin immune fab and Crofab, a mixture of Fabs forrattlesnake bites. Fabs againstcolchicine andtricyclic antidepressants has also been produced but are yet to see approval.[3][4] Compared to whole non-human antibodies, Fab' and F(ab')2 antibodies are less likely to triggeranaphylaxis, as the species-relatedFc region is removed.[5]
Fabs are a common form-factor formonoclonal antibodies designated for therapeutic use. The Fababciximab, which inhibits blood clotting, works bydisabling glycoprotein IIb/IIIa found onplatelets.[6]Ranibizumab, a treatment formacular degeneration, targetsvascular endothelial growth factor A, a protein involved in the growth of blood vessels.Certolizumab pegol is a Fabchemically linked to PEG, and it treats various inflammatory disorders by binding awayTNFα.
Fab antibodies also have diagnostic use.Arcitumomab is a mouse antibody that recognizescarcinoembryonic antigen, an antigen over-expressed in 95% of colorectal cancers. It is conjugated to a radioactive element, which will label the tumors when viewed withsingle-photon emission computed tomography.Sulesomab, an antigen that recognizes proteins on the surface ofgranulocytes, is used to label out infections, again using the99mTc isotope.[7]
Fab fragments are often fused to small proteins (<100 kDa) that have lower scattering, resulting in images with less contrast.
{{cite journal}}: CS1 maint: multiple names: authors list (link)Engineeredmonoclonal antibodies andantibody mimetics | ||
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| Whole antibody |  | |
| Fab fragment | ||
| Variable fragment | ||
| Smaller units | ||
| Intracellular | ||
| Antibody mimetics | ||