The fragment antigen-binding region ( Fab region) is a region on an antibody that binds to . It is composed of one constant and one variable domain of each of the heavy and the light chain. The variable domain contains the paratope (the antigen-binding site), comprising a set of complementarity-determining regions, at the N-terminus of the monomer. Each arm of the Y thus binds an epitope on the antigen.
Preparation
In an experimental setting,
fc region and Fab fragments can be generated in the laboratory. The
enzyme papain can be used to cleave an
immunoglobulin monomer into two Fab fragments and an Fc fragment. Conversely, the enzyme
pepsin cleaves below the hinge region, so the result instead is a
F(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 from
Streptococcus pyogenes, trade name FabRICATOR) cleaves
Immunoglobulin G in a sequence specific manner at neutral pH. The F(ab')
2 fragment can be split into two
Fab' fragments by mild
redox.
yields three fragments: two Fab fragments and one Fc fragment]]
yields two fragments: a F(ab')2 fragment and a pFc' fragment]]
The variable regions of the heavy and light chains can be fused together to form a single-chain variable fragment (scFv), which is only half the size of the Fab fragment, yet retains the original specificity of the parent immunoglobulin.
Applications
Therapeutics
Fabs have seen some therapeutic use in emergency medicine as an antidote. Marketed applications include digoxin immune fab and Crofab, a mixture of Fabs for
rattlesnake bites. Fabs against
colchicine and tricyclic antidepressants has also been produced but are yet to see approval.
Compared to whole non-human antibodies, Fab' and F(ab')
2 antibodies are less likely to trigger
anaphylaxis, as the species-related
Fc region is removed.
Fabs are a common form-factor for monoclonal antibodies designated for therapeutic use. The Fab abciximab, which inhibits blood clotting, works by disabling glycoprotein IIb/IIIa found on .[Fachinformation Lucentis. Novartis Pharma. Stand 15. November 2007.] Ranibizumab, a treatment for macular degeneration, targets vascular endothelial growth factor A, a protein involved in the growth of blood vessels. Certolizumab pegol is a Fab PEGylation, and it treats various inflammatory disorders by binding away TNFα.
Diagnostics
Fab antibodies also have diagnostic use.
Arcitumomab is a mouse antibody that recognizes carcinoembryonic antigen, an antigen over-expressed in 95% of colorectal cancers. It is conjugated to a radioactive element, which will label the tumors when viewed with single-photon emission computed tomography.
Sulesomab, an antigen that recognizes proteins on the surface of
, is used to label out infections, again using the
99mTc isotope.
Fab fragments are often fused to small proteins (<100 kDa) that have lower scattering, resulting in images with less contrast.
See also
-
Fragment crystallizable region
