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Antigen-antibody interaction
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.
The antigens and antibodies combine by a process called agglutination. 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.
The first correct description of the antigen-antibody reaction was given by Richard J. Goldberg at the
University of Wisconsin in 1952." 2] It came to be known as "Goldberg's theory" (of antigen-antibody
reaction) [3]
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
dlinical laboratory for diagnostic 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.
Molecular basis
Immunity developed as an individual is exposed to antigens is called adaptive or acquired immunity,
in contrast to immunity developed at birth, which is innate immunity. Aequired immunity depends
upon the interaction between antigens and a group of proteins called antibodies produced by B cells of
the blood. There are many antibodies and each is specific for a particular type of antigen. Thus
immune response in acquired immunity is due to the precise binding of antigens to antibody. Only
very small area of the antigens and antibody molecules actually interact through complementary
binding sites, called epitopes in antigens and paratopes in antibody.'5)
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 the variable
(V) 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 (V,) and variable heavy chain(Vj) creates three hypervariable regions (HV1, HV2, and HV3). In
V;, 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 may be part of a paratope, the part of an antibody
that recognizes and binds to an 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,
FRg, and FR4 lls]
Properties
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.(7I[8] Non-covalent bonds between antibody and
antigen can also be mediated by interfacial water molecules. Such
indirect bonds can contribute to the phenomenon of cross-
reactivity, i.e. the recognition of different but related antigens by a
single antibody.!9!
Affinity of the interaction
Antigen and antibody interact through a high affinity binding
much like lock and key.2°) 4 dynamic equilibrium exists for the
Structural model of an antibody
molecule. Rounded portions indicate
antigen binding sites.
Structure of hen egg lysozyme
(HEL) antigen. (A)
of HEL (CPK represen
together with three Abs (ribbon
representation). (B) The structure of
HEL colored according to the si
three epitopes as in (A). (C)
3D structure
tion)
structure of HEL colored according
to the epitopes predicted by
Discotope (light blue), ellipr
(purple), and seppa (pink).
binding. For example, the reaction is a reversible one, and can be expressed as:!2")
[Ab] + [Ag] = [AbAg]
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 K, can therefore be represented as:
x, = hm _ Abas]
° ee ~ [AIR]
where Koy and Koyrare the association and dissociation rate constants, respectively.
Reciprocally, the equilibibrium dissociation constant K4 will be:
Kos _ [AbIIAs]
Ka=
*~ Fon [AbAg]The antibody-antigen binding kinetic can be deseribed by the rate equation of a second-order
reversible reaction. 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:
Pr
Kor [AbJ[Ag] e(n—r)
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).(!21l'3]
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.!41
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.[1511161
Autoimmune disease
Normally antibodies can detect and differentiate molecules from outside of the body and those
produced inside the body as a result of cellular activities. Self molecules as ignored by the immune
system. However, in certain conditions, the antibodies recognise self molecules as antigens and
triggers unexpected immune responses. This results in different autoimmune dis depending on
the type of antigens and antibodies involved. Such conditions are always harmful and sometimes
deadly. The exact nature of antibody-antigen interaction in autoimmune disease is not yet
understood. (7168)
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.""9! Sophisticated applications include ELISA,2°! enzyme-linked
immunospot (Elispot), immunofluorescence, and immunoelectrophoresis,(2#/1221l23)
Precipitation reaction
Soluble antigens combine with soluble antibodies in presence of an electrolyte at suitable temperature
and pH to form insoluble visible complex. This is called a precipitation reaction. It is used for
qualitative and quantitative determination of both antigen and antibody. It involves the reaction of
soluble antigen with soluble antibodies to form large interlocking aggravated called lattice.[24) 1t
occurs in two distinct stages. Firstly, the antigen and antibody rapidly form antigen-antibody
complexes within few seconds and this is followed by a slower reaction in which the antibody-antigen
complexes forms lattices that precipitate from the solution.(251[26)A special ring test is useful for diagnosis of anthrax and determination of adulteration in food. (27128)
Agglutination reaction
It acts on antigen-antibody reaction in which the antibodies cross-link particulate antigens resulting
in the visible clumping of the particle. There are two types, namely active and passive
agglutination. |29) They are used in blood tests for diagnosis of enteric fever.!921(31)
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