Specific elements of antibody structure, such as the number of Y units, and the type of heavy chain determines the isotype. Within the same species, isotypes are further classified into subtypes or subclasses. Among individuals and ethnic groups, and within the same species, there is allelic variation in subtypes; allelic variants of subtypes are known as allotypes.
In contrast, idiotypes are defined by the antigenic determinants in the variable regions of the heavy chain of antibodies, and are subdivided into two groups: the antigenic determinants found in the antibody-binding regions (also known as CDRs, or paratopes), or those found in proximity to the paratope, in the framework regions (See Antibody Structure for more information).
Schematic showing the structure of the types of antibodies found in nature
Single Chain Antibodies
There are two types of single chain antibodies: Heavy chain antibodies (HCAb or IgVHH), expressed by camelids, and Ig new Ag receptors (IgNAR), produced by cartilaginous fish. Camelids such as camels also express heterotetrameric antibodies including their own IgG and IgA.
A total of 12 isotypes have been discovered to date across species: the immunoglobulin (Ig) isotypes A, D, E, F, G, M, P, T/Z, X, Y, and W. The first of these isotypes, IgM, has perhaps been expressed by vertebrates since the transition from sea to land; it is found in all vertebrates, except for the “living fossil”, the coelacanth, which is thought to be a primeval sea migrant.
Sharks produce IgM, and their own immunoglobulin, IgW, in addition to a single-chain antibody (IgNAR). In addition to IgM, IgD, and IgA (or its analog IgX in frogs), are present in tetrapods, except for frogs and birds (e.g. chickens), which do not express IgD, and crocodiles, which express an additional immunoglobulin (IgD2).
Amphibians also encode IgP, which is both expressed at the surface of, and secreted from cells. IgT or IgZ is found in Teleostei, the class of fish that includes zebrafish, and where both IgT and its equivalent IgZ were discovered. Some non-mammals (e.g. birds, reptiles, and amphibians) produce IgY, from which IgG and IgE are thought to evolve.
Figure 1. Infographic displaying a phylogenetic tree showing the natural evolution of immunoglobulins across different animals
In mammals, there are five main Ig types (isotypes): IgM, IgD, IgG, IgA, and IgE (highlighted in yellow in the phylogenetic tree). Humans, pigs, dogs, and cats have the same isotypes as rats and mice (the animal names highlighted in yellow). Furthermore, cows have also evolved to express IgGs with an ultralong heavy (H) chain complementarity determining region (CDR) 3 (CDR H3). Finally, camels express IgM, IgD, IgG, IgA, IgE, and single chain (IgVHH) antibodies.