Immunoglobulin heavy chain
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The immunoglobulin heavy chain (IgH) is the large polypeptide subunit of 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 ...
(immunoglobulin). In human genome, the IgH gene loci are on chromosome 14. A typical antibody is composed of two immunoglobulin (Ig) heavy chains and two Ig light chains. Several different types of heavy chain exist that define the class or isotype of an antibody. These heavy chain types vary between different animals. All heavy chains contain a series of
immunoglobulin domain The immunoglobulin domain, also known as the immunoglobulin fold, is a type of protein domain that consists of a 2-layer sandwich of 7-9 antiparallel β-strands arranged in two β-sheets with a Greek key topology, consisting of about 125 amino ac ...
s, usually with one variable
domain Domain may refer to: Mathematics *Domain of a function, the set of input values for which the (total) function is defined **Domain of definition of a partial function **Natural domain of a partial function **Domain of holomorphy of a function * Do ...
(VH) that is important for binding
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. ...
and several constant domains (CH1, CH2, etc.). Production of a viable heavy chain is a key step in B cell maturation. If the heavy chain is able to bind to a surrogate light chain and move to the plasma membrane, then the developing B cell can begin producing its light chain. The heavy chain doesn't always have to bind to a light chain. Pre-B lymphocytes can synthesize heavy chain in the absence of light chain, which then can allow the heavy chain to bind to a heavy-chain binding protein.


In mammals


Classes

There are five types of mammalian immunoglobulin heavy chain: γ, δ, α, μ and ε. They define ''classes'' of immunoglobulins:
IgG Immunoglobulin G (Ig G) 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 ...
, IgD, IgA,
IgM Immunoglobulin M (IgM) is one of several isotypes of antibody (also known as immunoglobulin) that are produced by vertebrates. IgM is the largest antibody, and it is the first antibody to appear in the response to initial exposure to an antig ...
and
IgE Immunoglobulin E (IgE) is a type of antibody (or immunoglobulin (Ig) " isotype") that has been found only in mammals. IgE is synthesised by plasma cells. Monomers of IgE consist of two heavy chains (ε chain) and two light chains, with the ε c ...
, respectively. * Heavy chains α and γ have approximately 450 amino acids. * Heavy chains μ and ε have approximately 550 amino acids.


Regions

Each heavy chain has two regions: * a ''constant region'' (which is the same for all immunoglobulins of the same class but differs between classes). ** Heavy chains γ, α and δ have a constant region composed of three tandem (in a line next to each other) immunoglobulin domains but also have a hinge region for added flexibility. ** Heavy chains μ and ε have a constant region composed of four domains. * a ''variable region'' that differs between different
B cell B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...
s, but is the same for all immunoglobulins produced by the same B cell or B cell clone. The variable domain of any heavy chain is composed of a single immunoglobulin domain. These domains are about 110 amino acids long.


Cows

Cows, specifically ''
Bos taurus Cattle (''Bos taurus'') are large, domesticated, cloven-hooved, herbivores. They are a prominent modern member of the subfamily Bovinae and the most widespread species of the genus ''Bos''. Adult females are referred to as cows and adult ma ...
'', show a variation on the general mammalian theme in which the heavy chain CDR H3 region has adapted to produce a divergent repertoire of antibodies which present a "stalk and knob" antigen interaction surface instead of the more familiar bivalent tip surface. The bovine CDR is unusually long and contains unique sequence attributes which support the production of paired
cysteine Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, sometime ...
residues during
somatic hypermutation Somatic hypermutation (or SHM) is a cellular mechanism by which the immune system adapts to the new foreign elements that confront it (e.g. microbes), as seen during class switching. A major component of the process of affinity maturation, SHM div ...
. Thus, where in humans the somatic hypermutation step targets the
V(D)J recombination V(D)J recombination is the mechanism of somatic recombination that occurs only in developing lymphocytes during the early stages of T and B cell maturation. It results in the highly diverse repertoire of antibodies/immunoglobulins and T cell rece ...
process, the target in cows is on the creation of diverse
disulfide bond In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...
s and the generation of unique sets of loops which interact with antigen. A speculated evolutionary driver for this variation is the presence of a vastly more diverse microbial environment in the digestive system of the cow as a consequence of their being
ruminant Ruminants (suborder Ruminantia) are ungulate, hoofed herbivorous grazing or browsing mammals that are able to acquire nutrients from plant-based food by Enteric fermentation, fermenting it in a specialized stomach prior to digestion, principally ...
s.


In fish

Jawed fish Gnathostomata (; from Greek: (') "jaw" + (') "mouth") are the jawed vertebrates. Gnathostome diversity comprises roughly 60,000 species, which accounts for 99% of all living vertebrates, including humans. In addition to opposing jaws, living ...
appear to be the most primitive animals that are able to make antibodies like those described for mammals. However, fish do not have the same repertoire of antibodies that mammals possess. Three distinct Ig heavy chains have so far been identified in
bony fish Osteichthyes (), popularly referred to as the bony fish, is a diverse superclass of fish that have skeletons primarily composed of bone tissue. They can be contrasted with the Chondrichthyes, which have skeletons primarily composed of cartilag ...
. * The first identified was the μ (or ''mu'') heavy chain that is present in all jawed fish and is the heavy chain for what is thought to be the primordial immunoglobulin. The resulting antibody, IgM, is secreted as a
tetramer A tetramer () (''tetra-'', "four" + '' -mer'', "parts") is an oligomer formed from four monomers or subunits. The associated property is called ''tetramery''. An example from inorganic chemistry is titanium methoxide with the empirical formula Ti ...
in
teleost Teleostei (; Greek ''teleios'' "complete" + ''osteon'' "bone"), members of which are known as teleosts ), is, by far, the largest infraclass in the class Actinopterygii, the ray-finned fishes, containing 96% of all extant species of fish. Tel ...
fish instead of the typical
pentamer A pentamer is an entity composed of five sub-units. In chemistry, it applies to molecules made of five monomers. In biochemistry, it applies to macromolecules, in particular to pentameric proteins, made of five proteic sub-units. In microbiol ...
found in mammals and sharks. * The heavy chain (δ) for IgD was identified initially from the
channel catfish The channel catfish (''Ictalurus punctatus'') is North America's most numerous catfish species. It is the official fish of Kansas, Missouri, Iowa, Nebraska, and Tennessee, and is informally referred to as a "channel cat". In the United States, the ...
and
Atlantic salmon The Atlantic salmon (''Salmo salar'') is a species of ray-finned fish in the family Salmonidae. It is the third largest of the Salmonidae, behind Siberian taimen and Pacific Chinook salmon, growing up to a meter in length. Atlantic salmon are ...
and is now well documented for many teleost fish. * The third teleost Ig heavy chain gene was identified very recently and does not resemble any of the heavy chains so far described for mammals. This heavy chain, identified in both
rainbow trout The rainbow trout (''Oncorhynchus mykiss'') is a species of trout native to cold-water tributaries of the Pacific Ocean in Asia and North America. The steelhead (sometimes called "steelhead trout") is an anadromous (sea-run) form of the coasta ...
(τ) and
zebrafish The zebrafish (''Danio rerio'') is a freshwater fish belonging to the minnow family ( Cyprinidae) of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (and thus often ...
(ζ), could potentially form a distinct antibody isotype (IgT or IgZ) that may precede IgM in evolutionary terms. Similar to the situation observed for bony fish, three distinct Ig heavy chain isotypes have been identified in
cartilaginous fish Chondrichthyes (; ) is a class that contains the cartilaginous fishes that have skeletons primarily composed of cartilage. They can be contrasted with the Osteichthyes or ''bony fishes'', which have skeletons primarily composed of bone tissue ...
. With the exception of μ, these Ig heavy chain isotypes appear to be unique to cartilaginous fish. The resulting antibodies are designated IgW (also called IgX or IgNARC) and IgNAR (''immunoglobulin new antigen receptor''). The latter type is a
heavy-chain antibody A heavy-chain antibody is an antibody which consists only of two heavy chains and lacks the two light chains usually found in antibodies. In common antibodies, the antigen binding region consists of the variable domains of the heavy and light c ...
, an antibody lacking light chains, and can be used to produce
single-domain antibodies A single-domain antibody (sdAb), also known as a nanobody, is an antibody fragment consisting of a single monomeric variable antibody domain. Like a whole antibody, it is able to bind selectively to a specific antigen. With a molecular weight ...
, which are essentially the variable domain (VNAR) of an IgNAR. Shark single domain antibodies (VNARs) to tumor or viral antigens can be isolated from a large naïve nurse shark VNAR library using phage display technology. IgW has now also been found in the group of lobe finned fishes including the coelacanth and lungfish. The IgW1 and IgW2 in coelacanth has a usual (VD)n-Jn-C structure as well as having a large number of constant domains.


In amphibians

Frogs can synthesize IgX and IgY.


See also

*
Heavy-chain antibody A heavy-chain antibody is an antibody which consists only of two heavy chains and lacks the two light chains usually found in antibodies. In common antibodies, the antigen binding region consists of the variable domains of the heavy and light c ...


References


External links

*
Educational Resource for Heavy Chain Analysis
{{Immune_proteins Immune system