Antigen-antibody interaction, or antigen-antibody reaction, is a specific chemical interaction between antibodies produced by B cells of the white blood cells and antigens during immune reaction. It is the fundamental reaction in the body by which the body is protected from complex foreign molecules, such as pathogens and their chemical toxins. In the blood, the antigens are specifically and with high affinity bound by antibodies to form an antigen-antibody complex. The immune complex is then transported to cellular systems where it can be destroyed or deactivated.
Contents
- Antibody structure
- Chemical basis of antigen antibody interaction
- Affinity of the interaction
- Application
- References
The first correct description of the antigen-antibody reaction was given by Richard J. Goldberg at the University of Wisconsin in 1952. It came to be known as "Goldberg's theory" (of antigen-antibody reaction).
There are several types of antibodies and antigens, and each antibody is capable of binding only to a specific antigen. The specificity of the binding is due to specific chemical constitution of each antibody. The antigenic determinant or epitope is recognized by the paratope of the antibody, situated at the variable region of the polypeptide chain. The variable region in turn has hyper-variable regions which are unique amino acid sequences in each antibody. Antigens are bound to antibodies through weak and noncovalent interactions such as electrostatic interactions, hydrogen bonds, Van der Waals forces, and hydrophobic interactions.
The principles of specificity and cross-reactivity of the antigen-antibody interaction are useful in clinical laboratory for diagnositic purposes. One basic application is determination of ABO blood group. It is also used as a molecular technique for infection with different pathogens, such as HIV, microbes, and helminth parasites.
Antibody structure
In an antibody, the Fab (fragment, antigen-binding) region is formed from the amino-terminal end of both the light and heavy chains of the immunoglobulin polypeptide. This region called V (variable) domain is composed of amino acid sequences that define each type of antibody and their binding affinity to an antigen. The combined sequence of variable light chain (VL) and variable heavy chain (VH) creates three hypervariable regions (HV1, HV2, and HV3). In VL these are roughly from residues 28 to 35, from 49 to 59, and from 92 to 103, respectively. HV3 is the most variable part. Thus these regions are the paratope, the binding site of antigen. The rest of the V region between the hypervariable regions are called framework regions. Each V domain has four framework domains, namely FR1, FR2, FR3, and FR4.
Chemical basis of antigen-antibody interaction
Antibodies bind antigens through weak chemical interactions, and bonding is essentially non-covalent. Electrostatic interactions, hydrogen bonds, van der Waals forces, and hydrophobic interactions are all known to be involved depending on the interaction sites.
Affinity of the interaction
Antigen and antibody interact through a high affinity binding much like lock and key. A dynamic equilibrium exists for the binding. For example, the reaction is a reversible one, and can be expressed as:
where [Ab] is the antibody concentration and [Ag] is the antigen concentration, either in free ([Ab],[Ag]) or bound ([AbAg]) state.
The equilibrium association constant can therefore be represented as:
where K is the equilibrium constant.
Reciprocally the dissociation constant will be:
However, these equations are applicable only to a single epitope binding, i.e. one antigen on one antibody. Since the antibody necessarily has two paratopes, and in many circumstances complex binding occurs, the multiple binding equilibrium can be summed up as:
where, at equilibrium, c is the concentration of free ligand, r represents the ratio of the concentration of bound ligand to total antibody concentration and n is the maximum number of binding sites per antibody molecule (the antibody valence).
The overall strength of the binding of an antibody to an antigen is termed its avidity for that antigen. Since antibodies are bivalent or polyvalent, this is the sum of the strengths of individual antibody-antigen interactions. The strength of an individual interaction between a single binding site on an antibody and its target epitope is termed the affinity of that interaction.
Avidity and affinity can be judged by the dissociation constant for the interactions they describe. The lower the dissociation constant, the higher the avidity or affinity, and the stronger the interaction.
Application
Antigen-antibody interaction is used in laboratory techniques for serological test of blood compatibility and various pathogenic infections. The most basic is ABO blood group determination, which is useful for blood transfusion. Sophisticated applications include ELISA, enzyme-linked immunospot (Elispot), immunofluorescence, and immunoelectrophoresis.