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 respons ...
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' ...
(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
...
. 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
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 ...
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, w ...
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 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 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, w ...
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 as an antidote. Marketed applications include
digoxin immune fab and Crofab, a mixture of Fabs for
rattlesnake bites. Fabs against
colchicine
Colchicine is a medication used to treat gout and Behçet's disease. In gout, it is less preferred to NSAIDs or steroids. Other uses for colchicine include the management of pericarditis and familial Mediterranean fever. Colchicine is taken b ...
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 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
platelet
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby i ...
s.
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 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
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
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 tu ...
is a Fab
chemically linked to PEG, and it treats various inflammatory disorders by binding away
TNFα.
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
granulocytes, 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
References
Antibodies
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