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

antibody An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...

that binds to

antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, 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, a characterization of objects with substantial weight * Heavy, a wake turbulence category used by pilots and air traffic controllers to refer to aircraft with a maximum takeoff mass of 136,000 kgs or mo ...

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' ...

(the antigen-binding site), comprising a set of complementarity-determining regions, at the amino terminal end of the

monomer A monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or two- or three-dimensional network in a process called polymerization. Classification Chemis ...

. 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 part of an antibody that binds to the epitope is called a paratope. Although e ...

on the antigen.

Preparation

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

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

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 wi ...

can be used to cleave an

immunoglobulin An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...

monomer into two Fab fragments and an Fc fragment. Conversely, the enzyme

pepsin Pepsin is an endopeptidase that breaks down proteins into smaller peptides and amino acids. It is one of the main digestive enzymes in the digestive systems of humans and many other animals, where it helps digest the proteins in food. Pe ...

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 ''Streptococcus pyogenes'' is a species of Gram-positive, aerotolerant bacteria in the genus '' Streptococcus''. These bacteria are extracellular, and made up of non-motile and non-sporing cocci (round cells) that tend to link in chains. They ...

'', trade name FabRICATOR) cleaves

IgG Immunoglobulin G (IgG) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ant ...

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

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

Therapeutics

Fabs have seen some therapeutic use in

emergency medicine Emergency medicine is the medical specialty concerned with the care of illnesses or injuries requiring immediate medical attention. Emergency physicians (or "ER doctors") specialize in providing care for unscheduled and undifferentiated pa ...

as an antidote. Marketed applications include digoxin immune fab and Crofab, a mixture of Fabs for

rattlesnake Rattlesnakes are venomous snakes that form the genus, 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 sm ...

bites. Fabs against

colchicine Colchicine is a medication used to prevent and treat gout, to treat familial Mediterranean fever and Behçet's disease, and to reduce the risk of myocardial infarction. The American College of Rheumatology recommends colchicine, nonstero ...

and

tricyclic antidepressant Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants. TCAs were discovered in the early 1950s and were marketed later in the decade. They are named after their chemical structure, which contains ...

s 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 Anaphylaxis (Greek: 'up' + 'guarding') is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of the use of emergency medication on site. It typicall ...

, as the species-related

Fc region The fragment crystallizable region (Fc region) is the tail region of an antibody that interacts with cell surface receptors called Fc receptors and some proteins of the complement system. This region allows antibodies to activate the immune sys ...

is removed. Fabs are a common form-factor for

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

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

platelet Platelets or thrombocytes () are a part of blood whose function (along with the coagulation#Coagulation factors, coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a thrombus, blood clot. Platelets have no ...

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

, 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 encod ...

, 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), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation. TNF is produced primarily by activated macrophages, and induces inflammation by binding to its receptors o ...

Diagnostics

Fab antibodies also have diagnostic use.

Arcitumomab Technetium (99mTc) arcitumomab was a drug used for the diagnostic imaging of colorectal cancers, marketed by Immunomedics. It consisted 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 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 tomography, tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera ...

. Sulesomab, 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, that i ...

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

{{Engineered antibodies Antibodies

Preparation

Applications

Therapeutics

Diagnostics

See also

References