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The immunoglobulin heavy chain (IgH) is the large polypeptide subunit of an antibody

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...

 (immunoglobulin).

A typical antibody is composed of two immunoglobulin (Ig) heavy chains and two Ig light chains

Immunoglobulin light chain

]The immunoglobulin light chain is the small polypeptide subunit of an antibody .A typical antibody is composed of two immunoglobulin heavy chains and two Ig light chains.-In humans:...

. Several different types of heavy chain exist that define the class or isotype

Isotype (immunology)

An isotype usually refers to any related proteins/genes from a particular gene family. In immunology, the "immunoglobulin isotype" refers to the genetic variations or differences in the constant regions of the heavy and light chains...

 of an antibody. These heavy chain types vary between different animals. All heavy chains contain a series of immunoglobulin domain

Immunoglobulin domain

The immunoglobulin domain is a type of protein domain that consists of a 2-layer sandwich of between 7 and 9 antiparallel β-strands arranged in two β-sheets with a Greek key topology....

s, usually with one variable domain (V_H) that is important for binding antigen

Antigen

An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...

 and several constant domains (C_H1, C_H2, etc).

Classes

There are five types of mammalian immunoglobulin heavy chain: γ, δ, α, μ and ε. They define classes of immunoglobulins: IgG, IgD

IGD

IGD can refer to:*Internet Gateway Device as defined in UPnP.*İGD, İlerici Gençler Derneği, Progressive Young Association of Turkey*Immunoglobulin D, an antibody protein involved in the maturation of B cells....

, IgA

IGA

Iga or IGA may stand for:-Given name:* a female given name of Polish origin. The name originates from the female given name Jadwiga and stands for gia,or gina in the USA....

, IgM

IGM

IGM as an acronym or abbreviation can refer to:* Immunoglobulin M , the primary antibody against A and B antigens on red blood cells* International Grandmaster, a chess ranking* intergalactic medium* Intragroup medium - see: Intracluster medium...

 and IgE

IGE

IGE was one of the largest services company buying and selling virtual currencies and accounts for MMORPG. During its peak time, it had offices in Los Angeles, China , and headquarters & customer service centre in Hong Kong. IGE was one of the main monopoly in virtual economy services, also known...

, 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 cell
  B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
  
  s, but is the same for all immunoglobulins produced by the same B cell or B cell clone
  Clone (B-cell biology)
  The process of immunological B-cell maturation involves transformation from an undifferentiated B cell to one that secretes antibodies with particular specificity...
  
  . The variable domain of any heavy chain is composed of a single immunoglobulin domain. These domains are about 110 amino acids long.

In fish

Jawed fish 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.

• 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
  Tetramer
  A tetramer is a protein with four subunits . There are homotetramers such as glutathione S-transferase or single-strand binding protein, dimers of hetero-dimers such as hemoglobin , and heterotetramers, where each subunit is different.-Subunit interactions in tetramers:The interactions between...
  
   in teleost fish instead of the typical pentamer
  Pentamer
  A pentamer is a thing composed out 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....
  
   found in mammals and sharks.

• The heavy chain (δ) for IgD was identified initially from the channel catfish
  Channel catfish
  Channel catfish, Ictalurus punctatus, is North America's most numerous catfish species. It is the official fish of Missouri, Iowa, Nebraska, Kansas, and Tennessee, and is informally referred to as a "channel cat". In the United States they are the most fished catfish species with approximately 8...
  
   and Atlantic salmon
  Atlantic salmon
  The Atlantic salmon is a species of fish in the family Salmonidae, which is found in the northern Atlantic Ocean and in rivers that flow into the north Atlantic and the north Pacific....
  
   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
  Rainbow trout
  The rainbow trout is a species of salmonid native to tributaries of the Pacific Ocean in Asia and North America. The steelhead is a sea run rainbow trout usually returning to freshwater to spawn after 2 to 3 years at sea. In other words, rainbow trout and steelhead trout are the same species....
  
   (τ) and zebrafish (ζ), could potentially form a distinct antibody isotype
  Isotype (immunology)
  An isotype usually refers to any related proteins/genes from a particular gene family. In immunology, the "immunoglobulin isotype" refers to the genetic variations or differences in the constant regions of the heavy and light chains...
  
   (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. 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, an antibody lacking light chains, and can be used to produce single-domain antibodies, which are essentially the variable domain of an IgNAR.

External links

• Educational Resource for Heavy Chain Analysis