Hapten
Encyclopedia
A hapten is a small molecule
that can elicit an immune response only when attached to a large carrier such as a protein
; the carrier may be one that also does not elicit an immune response by itself. (In general, only large molecules, infectious agents, or insoluble foreign matter can elicit an immune response in the body.)
Once the body has generated antibodies
to a hapten-carrier adduct
, the small-molecule hapten may also be able to bind to the antibody, but it will usually not initiate an immune response; usually only the hapten-carrier adduct can do this. Sometimes the small-molecule hapten can even block immune response to the hapten-carrier adduct by preventing the adduct from binding to the antibody, a process called hapten inhibition.
The mechanisms of absence of immune response may vary and involve complex immunological mechanisms, but can include absent or insufficient co-stimulatory signals from antigen-presenting cell
s.
The concept of haptens emerged from the work of Karl Landsteiner
who also pioneered the use of synthetic haptens to study immunochemical phenomena.
and its carboxyl derivatives (o-
, m-
, and p-aminobenzoic acid
).
A well-known example of a hapten is urushiol
, which is the toxin found in poison ivy. When absorbed through the skin from a poison ivy plant, urushiol undergoes oxidation in the skin cells to generate the actual hapten, a reactive molecule called a quinone
, which then reacts with skin proteins to form hapten adducts. Usually, the first exposure causes only sensitization, in which there is a proliferation of effector T-cells. After a second exposure later, the proliferated T cells can become activated, generating an immune reaction, producing the typical blisters of poison ivy exposure.
Some haptens can induce autoimmune disease. An example is hydralazine
, a blood pressure-lowering drug that occasionally can produce drug-induced lupus erythematosus
in certain individuals. This also appears to be the mechanism by which the anaesthetic gas halothane
can cause a life-threatening hepatitis
, as well as the mechanism by which penicillin
-class drugs cause autoimmune hemolytic anemia
.
Other haptens that are commonly used in molecular biology applications include fluorescein
, biotin
, digoxigenin
, and dinitrophenol
.
response towards a molecule by introducing a fraction of it that works as a hapten. The rest of the molecule may be regarded as the carrier, and the entire molecule as the adduct. The hapten binds up antibodies toward that molecule without causing the immune response, leaving less antibodies left to bind to the molecule itself. An example of a hapten inhibitor is dextran 1
, which is a small fraction (1 kilodalton) of the entire dextran complex, which is enough to bind anti-dextran antibodies, but insufficient to result in the formation of immune complex
es and resultant immune responses.
Small molecule
In the fields of pharmacology and biochemistry, a small molecule is a low molecular weight organic compound which is by definition not a polymer...
that can elicit an immune response only when attached to a large carrier such as a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
; the carrier may be one that also does not elicit an immune response by itself. (In general, only large molecules, infectious agents, or insoluble foreign matter can elicit an immune response in the body.)
Once the body has generated antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
to a hapten-carrier adduct
Adduct
An adduct is a product of a direct addition of two or more distinct molecules, resulting in a single reaction product containing all atoms of all components. The resultant is considered a distinct molecular species...
, the small-molecule hapten may also be able to bind to the antibody, but it will usually not initiate an immune response; usually only the hapten-carrier adduct can do this. Sometimes the small-molecule hapten can even block immune response to the hapten-carrier adduct by preventing the adduct from binding to the antibody, a process called hapten inhibition.
The mechanisms of absence of immune response may vary and involve complex immunological mechanisms, but can include absent or insufficient co-stimulatory signals from antigen-presenting cell
Antigen-presenting cell
An antigen-presenting cell or accessory cell is a cell that displays foreign antigen complexes with major histocompatibility complex on their surfaces. T-cells may recognize these complexes using their T-cell receptors...
s.
The concept of haptens emerged from the work of Karl Landsteiner
Karl Landsteiner
Karl Landsteiner , was an Austrian-born American biologist and physician of Jewish origin. He is noted for having first distinguished the main blood groups in 1900, having developed the modern system of classification of blood groups from his identification of the presence of agglutinins in the...
who also pioneered the use of synthetic haptens to study immunochemical phenomena.
Examples of haptens
The first haptens used were anilineAniline
Aniline, phenylamine or aminobenzene is an organic compound with the formula C6H5NH2. Consisting of a phenyl group attached to an amino group, aniline is the prototypical aromatic amine. Being a precursor to many industrial chemicals, its main use is in the manufacture of precursors to polyurethane...
and its carboxyl derivatives (o-
Anthranilic acid
Anthranilic acid is the organic compound with the formula C6H4COOH. This amino acid is a white solid when pure, although commercial samples may appear yellow. The molecule consists of a benzene ring with two adjacent functional groups, a carboxylic acid and an amine...
, m-
3-Aminobenzoic acid
3-Aminobenzoic acid is an organic compound with the molecular formula C7H7NO2. MABA is a white to yellowish-red crystalline substance that is only slightly soluble in water. It consists of a benzene ring substituted with an amino group and a carboxylic acid....
, and p-aminobenzoic acid
4-Aminobenzoic acid
4-Aminobenzoic acid is an organic compound with the formula H2NC6H4CO2H. PABA is a white grey crystalline substance that is only slightly soluble in water...
).
A well-known example of a hapten is urushiol
Urushiol
Urushiol is an oily organic allergen found in plants of the family Anacardiaceae, especially Toxicodendron spp. . It causes an allergic skin rash on contact, known as urushiol-induced contact dermatitis...
, which is the toxin found in poison ivy. When absorbed through the skin from a poison ivy plant, urushiol undergoes oxidation in the skin cells to generate the actual hapten, a reactive molecule called a quinone
Quinone
A quinone is a class of organic compounds that are formally "derived from aromatic compounds [such as benzene or naphthalene] by conversion of an even number of –CH= groups into –C– groups with any necessary rearrangement of double bonds," resulting in "a fully conjugated cyclic dione structure."...
, which then reacts with skin proteins to form hapten adducts. Usually, the first exposure causes only sensitization, in which there is a proliferation of effector T-cells. After a second exposure later, the proliferated T cells can become activated, generating an immune reaction, producing the typical blisters of poison ivy exposure.
Some haptens can induce autoimmune disease. An example is hydralazine
Hydralazine
Hydralazine is a direct-acting smooth muscle relaxant used to treat hypertension by acting as a vasodilator primarily in arteries and arterioles...
, a blood pressure-lowering drug that occasionally can produce drug-induced lupus erythematosus
Lupus erythematosus
Lupus erythematosus is a category for a collection of diseases with similar underlying problems with immunity . Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs...
in certain individuals. This also appears to be the mechanism by which the anaesthetic gas halothane
Halothane
Halothane is an inhalational general anesthetic. Its IUPAC name is 2-bromo-2-chloro-1,1,1-trifluoroethane. It is the only inhalational anesthetic agent containing a bromine atom; there are several other halogenated anesthesia agents which lack the bromine atom and do contain the fluorine and...
can cause a life-threatening hepatitis
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
, as well as the mechanism by which penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....
-class drugs cause autoimmune hemolytic anemia
Hemolytic anemia
Hemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells , either in the blood vessels or elsewhere in the human body . It has numerous possible causes, ranging from relatively harmless to life-threatening...
.
Other haptens that are commonly used in molecular biology applications include fluorescein
Fluorescein
Fluorescein is a synthetic organic compound available as a dark orange/red powder soluble in water and alcohol. It is widely used as a fluorescent tracer for many applications....
, biotin
Biotin
Biotin, also known as Vitamin H or Coenzyme R, is a water-soluble B-complex vitamin discovered by Bateman in 1916. It is composed of a ureido ring fused with a tetrahydrothiophene ring. A valeric acid substituent is attached to one of the carbon atoms of the tetrahydrothiophene ring...
, digoxigenin
Digoxigenin
Digoxigenin is a steroid found exclusively in the flowers and leaves of the plants Digitalis purpurea, Digitalis orientalis and Digitalis lanata , where it is attached to sugars, to form the glycosides Digoxigenin (DIG) is a steroid found exclusively in the flowers and leaves of the plants...
, and dinitrophenol
2,4-Dinitrophenol
2,4-Dinitrophenol , C6H4N2O5, is a cellular metabolic poison. It uncouples oxidative phosphorylation by carrying protons across the mitochondrial membrane, leading to a rapid consumption of energy without generation of ATP....
.
Hapten inhibition
Hapten inhibition is the inhibition of a type III hypersensitivityType III hypersensitivity
Type III hypersensitivity occurs when antigens and antibodies are present in roughly equal amounts, causing extensive cross-linking.-Presentation:...
response towards a molecule by introducing a fraction of it that works as a hapten. The rest of the molecule may be regarded as the carrier, and the entire molecule as the adduct. The hapten binds up antibodies toward that molecule without causing the immune response, leaving less antibodies left to bind to the molecule itself. An example of a hapten inhibitor is dextran 1
Dextran 1
Dextran 1 is a hapten inhibitor that greatly reduces the risk for anaphylactic reactions when administering dextran.-Mechanism:Dextran 1 is composed of a small fraction of the entire dextran complex. This is enough to bind anti-dextran antibodies, but insufficient to result in the formation of...
, which is a small fraction (1 kilodalton) of the entire dextran complex, which is enough to bind anti-dextran antibodies, but insufficient to result in the formation of immune complex
Immune complex
An immune complex is formed from the integral binding of an antibody to a soluble antigen. The bound antigen acting as a specific epitope, bound to an antibody is referred to as a singular immune complex....
es and resultant immune responses.