Immunoglobulin heavy chain

There are five types of mammalian immunoglobulin heavy chain: γ, δ, α, μ and ε.^[4] They define classes of immunoglobulins: IgG, IgD, IgA, IgM and IgE, respectively.

• Heavy chains α and γ have approximately 450 amino acids.
• Heavy chains μ and ε have approximately 550 amino acids.^[4]

Each heavy chain has two regions:

• aconstant 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.^[5]
  • Heavy chains μ and ε have a constant region composed of four domains.^[4]
• avariable region that differs between different B cells, 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.^[6]

Cows, specifically Bos taurus, 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.^[7] The bovine CDR is unusually long and contains unique sequence attributes which support the production of paired cysteine residues during somatic hypermutation.^[7] Thus, where in humans the somatic hypermutation step targets the V(D)J recombination process, the target in cows is on the creation of diverse disulfide bonds and the generation of unique sets of loops which interact with antigen.^[7] 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 ruminants.^[7]

Jawed fish appear to be the most primitive animals that are able to make antibodies like those described for mammals.^[8] However, fish do not have the same repertoire of antibodies that mammals possess.^[9] Three distinct Ig heavy chains have so far been identified in bony fish.

• The first identified was the μ (ormu) 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 tetramerinteleost fish instead of the typical pentamer found in mammals and sharks.^{[citation needed]}
• The heavy chain (δ) for IgD was identified initially from the channel catfish and Atlantic salmon and is now well documented for many teleost fish.^[10]
• 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 (τ)^[11] and zebrafish (ζ),^[12] 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. 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).^[13][14] 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 (V_NAR) of an IgNAR.^[15][16][17] Shark single domain antibodies (V_NARs) to tumor or viral antigens can be isolated from a large naïve nurse shark V_NAR library using phage display technology.^[16][18]

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.^[19][20]

Frogs can synthesize IgX and IgY. ^[21]

• Heavy-chain antibody

• Immunoglobulin+Heavy+Chains at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Educational Resource for Heavy Chain Analysis