The fragment antigen-binding region (Fab region) is a region on an

antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

that binds to

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

s. It is composed of one constant and one variable domain of each of the

heavy Heavy may refer to: Measures * Heavy (aeronautics), a term used by pilots and air traffic controllers to refer to aircraft capable of 300,000 lbs or more takeoff weight * Heavy, a characterization of objects with substantial weight * Heavy, ...

and the light chain. The variable domain contains the

paratope In immunology, a paratope, also known as an antigen-binding site, is the part of an antibody which recognizes and binds to an antigen. It is a small region at the tip of the antibody's antigen-binding fragment and contains parts of the antibody's ...

(the antigen-binding site), comprising a set of

complementarity-determining region Complementarity-determining regions (CDRs) are part of the variable chains in immunoglobulins (antibodies) and T cell receptors, generated by B-cells and T-cells respectively, where these molecules bind to their specific antigen. A set of CDRs co ...

s, at the amino terminal end of the monomer. Each arm of the Y thus binds an

epitope An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The epitope is the specific piece of the antigen to which an antibody binds. The p ...

on the antigen.

Preparation

In an experimental setting, Fc 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 Pepsin is an endopeptidase that breaks down proteins into smaller peptides. It is produced in the gastric chief cells of the stomach lining and is one of the main digestive enzymes in the digestive systems of humans and many other animals, ...

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 IgG in a sequence specific manner at neutral pH. The F(ab')₂ fragment can be split into two Fab' fragments by mild reduction. File:Antibody je2.png, Heavy and light chains, variable and constant regions of an antibody. File:2fab fc.svg, An antibody digested by papain yields three fragments: two Fab fragments and one Fc fragment File:F ab2 pFc.png, An antibody digested by

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 A single-chain variable fragment (scFv) is not actually a fragment of an antibody, but instead is a fusion protein of the variable regions of the heavy (VH) and light chains (VL) of immunoglobulins, connected with a short linker peptide of t ...

(scFv), which is only half the size of the Fab fragment, yet retains the original specificity of the parent immunoglobulin.

Applications

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 Rattlesnakes are venomous snakes that form the genera ''Crotalus'' and ''Sistrurus'' of the subfamily Crotalinae (the pit vipers). All rattlesnakes are vipers. Rattlesnakes are predators that live in a wide array of habitats, hunting small anima ...

bites. Fabs against colchicine and tricyclic antidepressants has also been produced but are yet to see approval. Fabs are a common form-factor for monoclonal antibodies designated for therapeutic use. The Fab

abciximab Abciximab, a glycoprotein IIb/IIIa receptor antagonist manufactured by Janssen Biologics BV and distributed by Eli Lilly under the trade name ReoPro, is a platelet aggregation inhibitor mainly used during and after coronary artery procedures li ...

, which inhibits blood clotting, works by disabling glycoprotein IIb/IIIa found on platelets.

Ranibizumab Ranibizumab, sold under the brand name Lucentis among others, is a monoclonal antibody fragment ( Fab) created from the same parent mouse antibody as bevacizumab. It is an anti-angiogenic that is approved to treat the "wet" type of age-related ...

, a treatment for macular degeneration, targets

vascular endothelial growth factor A Vascular endothelial growth factor A (VEGF-A) is a protein that in humans is encoded by the ''VEGFA'' gene. Function This gene is a member of the platelet-derived growth factor (PDGF)/vascular endothelial growth factor (VEGF) family and enco ...

, a protein involved in the growth of blood vessels.

Certolizumab pegol Certolizumab pegol, sold under the brand name Cimzia, is a biologic medication for the treatment of Crohn's disease, rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. It is a fragment of a monoclonal antibody specific to tumor ...

is a Fab chemically linked to PEG, and it treats various inflammatory disorders by binding away

TNFα Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...

. Fab antibodies also have diagnostic use. Arcitumomab is a mouse antibody that recognizes

carcinoembryonic antigen Carcinoembryonic antigen (CEA) describes a set of highly related glycoproteins involved in cell adhesion. CEA is normally produced in gastrointestinal tissue during fetal development, but the production stops before birth. Consequently, CEA is us ...

, 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 Single-photon emission computed tomography (SPECT, or less commonly, SPET) is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera (that is, ...

Sulesomab Technetium (99mTc) sulesomab (trade name LeukoScan) is a radio-pharmaceutical composed of anti-human mouse monoclonal antibody that targets the granulocyte associated NCA-90 cell antigen and a conjugated technetium-99m radionuclide. After intrav ...

, an antigen that recognizes proteins on the surface of

granulocyte Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear. They ha ...

s, 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.

References

Antibodies {{immunology-stub

Preparation

Applications

See also

References