User:Spaully/WIP Antibody

Structure of the antibody

Immunoglobulins are heavy plasma proteins, often with added sugar chains (see glycosylation) on N-terminal (all antibodies) and occasionally O-terminal (IgA1 and IgD) amino acid residues.

The basic unit of each antibody is a monomer. An antibody can be monomeric, dimeric, trimeric, tetrameric, pentameric, etc. The monomer is a "Y"-shape molecule that consists of two identical heavy chains and two identical light chains connected by disulfide bonds.

There are five types of heavy chain: γ, δ, α, μ and ε. They define classes of immunoglobulins. Heavy chains α and γ have approximately 450 amino acids, while μ and ε have approximately 550 amino acids. Each heavy chain has a constant region, which is the same by all immunoglobulins of the same class, and a variable region, which differs between immunoglobulins of different B cells, but is the same for all immunoglobulins produced by the same B cell. Heavy chains γ, α and δ have the constant region composed of three domains; the constant region of heavy chains μ and ε is composed of four domains. The variable domain of any heavy chain is composed of one domain. These domains are about 110 amino acids long. There are also some amino acids between constant domains.

There are only two types of light chain: λ and κ. In humans, they are similar, but only one type is present in each antibody. Each light chain has two successive domains: one constant and one variable domain. The approximate length of a light chain is from 211 to 217 amino acids.

The monomer is composed of two heavy and two light chains. Together this gives six to eight constant domains and four variable domains. If it is cleaved with enzymes papain and pepsin, we get two Fab (fragment binding antigen) fragments and an Fc (fragment crystallizable) fragment.

Each half of the forked end of the "Y"-shape monomer is called the Fab fragment. It is composed of one constant and one variable domain of each the heavy and the light chain, which together shape the antigen binding site at the amino terminal end of the monomer. The two variable domains bind the antigens they are specific for and that elicited their production.

The ability to bind a wide variety of foreign antigens arises from events known as somatic recombination. This is when genes are selected (variable (V), diversity (D) and joining (J) for heavy chains, and only V and J for light chains) to form countless combinations. The main reason that the human immune system is capable of binding so many antigens is the variable region of the heavy chain. To be specific, it is the area where these V, D and J genes are found - otherwise known as the complementarity determining region 3 (CDR3).

The Fc fragment is the stem of the "Y" and is composed from two heavy chains that each contribute two to three constant domains (depending on the class of the antibody). It binds to various cell receptors and complement proteins. In this way it mediates different physiological effects of antibodies (opsonization, cell lysis, mast cell, basophil and eosinophil degranulation and other processes).

The variable regions of the heavy and light chains can be fused together to form a single chain variable fragment (scFv), which retains the original specificity of the parent immunoglobulin.

A crude estimation of immunoglobulin levels can be made by protein electrophoresis. Here the plasma proteins are separated into albumin, alpha-globulins (1 and 2), beta-globulins (1 and 2) and gamma-globulins according to weight. Immunoglobulins are all in the gamma region. In some disease states (myeloma) a very high concentration of one particular immunoglobulin will show up as a monoclonal band.

Generating antibody diversity

There are about 10⁹ B lymphocytes in the body, and each one will produce a different antibody all of which will have specificity for different antigens. They will all have different primary structures, corresponding to thier coding gene. However the human genome only has 20,000 or so coding genes. ....

Isotypes

According to differences in their heavy chain constant domains, immunoglobulins are grouped into five classes or isotypes: IgG, IgA, IgM, IgD, and IgE. (The isotypes are also defined with light chains, but they do not define classes, so they are often neglected.) Other immune cells partner with antibodies to eliminate pathogens depending on which IgG, IgA, IgM, IgD, and IgE constant binding domain receptors it can express on its surface.

The antibodies that a single B lymphocyte produces can differ in their heavy chain and the B cell often expresses different classes of antibodies at the same time. However, they are identical in their specificity for antigen, conferred by their variable region. To achieve the large number of specificities the body needs to protect itself against many different foreign antigens, it must produce millions of B lymphoyctes. It is important to note that, in order to produce such a diversity of antigen binding sites with a separate gene for each possible antigen, the immune system would require many more genes than exist in the genome. Instead, as Susumu Tonegawa showed in 1976, portions of the genome in B lymphocytes can recombine to form all the variation seen in the antibodies and more. Tonegawa won the Nobel Prize in Physiology or Medicine in 1987 for his discovery.