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 and the light chain. The variable domain contains the paratope (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 In chemistry, a monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or three-dimensional network in a process called polymerization. Classification Mo ...

. Each arm of the Y thus binds an epitope on the antigen.

Preparation

In an experimental setting, Fc and Fab fragments can be generated in the laboratory. The

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

papain Papain, also known as papaya proteinase I, is a cysteine protease () enzyme present in papaya (''Carica papaya'') and mountain papaya (''Vasconcellea cundinamarcensis''). It is the namesake member of the papain-like protease family. It has wide ...

can be used to cleave an

immunoglobulin 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 ...

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 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

yields three fragments: two Fab fragments and one Fc fragment File:F ab2 pFc.png, An antibody digested by pepsin 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 ten ...

(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 Emergency medicine is the medical speciality concerned with the care of illnesses or injuries requiring immediate medical attention. Emergency physicians (often called “ER doctors” in the United States) continuously learn to care for unsche ...

as an antidote. Marketed applications include

digoxin immune fab Digoxin immune fab or digoxin-specific antibody is an antidote for overdose of digoxin. It is made from Antibody, immunoglobulin fragments from sheep that have already been immunized with a digoxin derivative, digoxindicarboxymethoxylamine (DDMA). ...

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 anim ...

bites. Fabs against colchicine and

tricyclic antidepressant Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and wer ...

s has also been produced but are yet to see approval. Fabs are a common form-factor for

monoclonal antibodies A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ca ...

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 lik ...

, 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 m ...

, a treatment for

macular degeneration Macular degeneration, also known as age-related macular degeneration (AMD or ARMD), is a medical condition which may result in blurred or no vision in the center of the visual field. Early on there are often no symptoms. Over time, however, som ...

, targets vascular endothelial growth factor A, a protein involved in the growth of blood vessels. Certolizumab pegol 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 Technetium (99mTc) arcitumomab is a drug used for the diagnostic imaging of colorectal cancers, marketed by Immunomedics. It consists of the Fab' fragment of a monoclonal antibody (arcitumomab, trade name CEA-Scan) and a radionuclide, technetiu ...

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 ...

, 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 intrave ...

, 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