Antigen-antibody interaction

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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.

Contents

The first correct description of the antigen-antibody reaction was given by Richard J. Goldberg at the University of Wisconsin in 1952. [1] [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. [4]

The principles of specificity and cross-reactivity of the antigen-antibody interaction are useful in clinical 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. Acquired 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

Structural model of an antibody molecule. Rounded portions indicate antigen binding sites. Structure of antibody molecule.jpg
Structural model of an antibody molecule. Rounded portions indicate antigen binding sites.

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 (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 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, FR3, and FR4. [4] [6]

Structure of hen egg lysozyme (HEL) antigen. (A) The 3-D structure of HEL (CPK representation) together with three Abs (ribbon representation). (B) The structure of HEL colored according to the same three epitopes as in (A). (C) The structure of HEL colored according to the epitopes predicted by Discotope (light blue), ellipro (purple), and seppa (pink). Epitope of HEL.jpg
Structure of hen egg lysozyme (HEL) antigen. (A) The 3-D structure of HEL (CPK representation) together with three Abs (ribbon representation). (B) The structure of HEL colored according to the same three epitopes as in (A). (C) The structure of HEL colored according to the epitopes predicted by Discotope (light blue), ellipro (purple), and seppa (pink).

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. [7] [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. [10] A dynamic equilibrium exists for the binding. For example, the reaction is a reversible one, and can be expressed as: [11]

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 Ka can therefore be represented as:

where kon and koff are the association and dissociation rate constants, respectively.

Reciprocally, the equilibibrium dissociation constant Kd will be:

The antibody-antigen binding kinetic can be described 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:

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). [12] [13]

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. [14]

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. [15] [16]

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 diseases 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. [17] [18]

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. [19] Sophisticated applications include ELISA, [20] enzyme-linked immunospot (Elispot), immunofluorescence, and immunoelectrophoresis. [21] [22] [23]

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] It 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. [25] [26]

A special ring test is useful for diagnosis of anthrax and determination of adulteration in food. [27] [28]

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. [30] [31]

Related Research Articles

<span class="mw-page-title-main">Antigen</span> Molecule triggering an immune response (antibody production) in the host

In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response.

<span class="mw-page-title-main">Antibody</span> Protein(s) forming a major part of an organisms immune system

An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that cause disease. Antibodies can recognize virtually any size antigen with diverse chemical compositions from molecules. Each antibody recognizes one or more specific antigens. Antigen literally means "antibody generator", as it is the presence of an antigen that drives the formation of an antigen-specific antibody. Each tip of the "Y" of an antibody contains a paratope that specifically binds to one particular epitope on an antigen, allowing the two molecules to bind together with precision. Using this mechanism, antibodies can effectively "tag" a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly.

In chemistry, biochemistry, and pharmacology, a dissociation constant (KD) is a specific type of equilibrium constant that measures the propensity of a larger object to separate (dissociate) reversibly into smaller components, as when a complex falls apart into its component molecules, or when a salt splits up into its component ions. The dissociation constant is the inverse of the association constant. In the special case of salts, the dissociation constant can also be called an ionization constant. For a general reaction:

Humoral immunity is the aspect of immunity that is mediated by macromolecules – including secreted antibodies, complement proteins, and certain antimicrobial peptides – located in extracellular fluids. Humoral immunity is named so because it involves substances found in the humors, or body fluids. It contrasts with cell-mediated immunity. Humoral immunity is also referred to as antibody-mediated immunity.

<span class="mw-page-title-main">Immunoglobulin G</span> Antibody isotype

Immunoglobulin G (IgG) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG antibody has two paratopes.

An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that binds to the epitope is called a paratope. Although epitopes are usually non-self proteins, sequences derived from the host that can be recognized are also epitopes.

Haptens are small molecules that elicit an immune response only when attached to a large carrier such as a protein; the carrier may be one that also does not elicit an immune response by itself. The mechanisms of absence of immune response may vary and involve complex immunological interactions, but can include absent or insufficient co-stimulatory signals from antigen-presenting cells.

Opsonins are extracellular proteins that, when bound to substances or cells, induce phagocytes to phagocytose the substances or cells with the opsonins bound. Thus, opsonins act as tags to label things in the body that should be phagocytosed by phagocytes. Different types of things ("targets") can be tagged by opsonins for phagocytosis, including: pathogens, cancer cells, aged cells, dead or dying cells, excess synapses, or protein aggregates. Opsonins help clear pathogens, as well as dead, dying and diseased cells.

<span class="mw-page-title-main">T-cell receptor</span> Protein complex on the surface of T cells that recognizes antigens

The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding between TCR and antigen peptides is of relatively low affinity and is degenerate: that is, many TCRs recognize the same antigen peptide and many antigen peptides are recognized by the same TCR.

<span class="mw-page-title-main">Epitope mapping</span> Identifying the binding site of an antibody on its target antigen

In immunology, epitope mapping is the process of experimentally identifying the binding site, or epitope, of an antibody on its target antigen. Identification and characterization of antibody binding sites aid in the discovery and development of new therapeutics, vaccines, and diagnostics. Epitope characterization can also help elucidate the binding mechanism of an antibody and can strengthen intellectual property (patent) protection. Experimental epitope mapping data can be incorporated into robust algorithms to facilitate in silico prediction of B-cell epitopes based on sequence and/or structural data.

Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted:

<span class="mw-page-title-main">Immune complex</span> Molecule formed binding antigens to antibodies

An immune complex, sometimes called an antigen-antibody complex or antigen-bound antibody, is a molecule formed from the binding of multiple antigens to antibodies. The bound antigen and antibody act as a unitary object, effectively an antigen of its own with a specific epitope. After an antigen-antibody reaction, the immune complexes can be subject to any of a number of responses, including complement deposition, opsonization, phagocytosis, or processing by proteases. Red blood cells carrying CR1-receptors on their surface may bind C3b-coated immune complexes and transport them to phagocytes, mostly in liver and spleen, and return to the general circulation.

Cross-reactivity, in a general sense, is the reactivity of an observed agent which initiates reactions outside the main reaction expected. This has implications for any kind of test or assay, including diagnostic tests in medicine, and can be a cause of false positives. In immunology, the definition of cross-reactivity refers specifically to the reaction of the immune system to antigens. There can be cross-reactivity between the immune system and the antigens of two different pathogens, or between one pathogen and proteins on non-pathogens, which in some cases can be the cause of allergies.

<span class="mw-page-title-main">Paratope</span> Part of an antibody which binds to an antigen

In immunology, a paratope, also known as an antigen-binding site, is the part of an antibody which recognizes and binds to an antigen. It is a small region at the tip of the antibody's antigen-binding fragment and contains parts of the antibody's heavy and light chains. Each paratope is made up of six complementarity-determining regions - three from each of the light and heavy chains - that extend from a fold of anti-parallel beta sheets. Each arm of the Y-shaped antibody has an identical paratope at the end.

In biochemistry, avidity refers to the accumulated strength of multiple affinities of individual non-covalent binding interactions, such as between a protein receptor and its ligand, and is commonly referred to as functional affinity. Avidity differs from affinity, which describes the strength of a single interaction. However, because individual binding events increase the likelihood of occurrence of other interactions, avidity should not be thought of as the mere sum of its constituent affinities but as the combined effect of all affinities participating in the biomolecular interaction. A particular important aspect relates to the phenomenon of 'avidity entropy'. Biomolecules often form heterogenous complexes or homogeneous oligomers and multimers or polymers. If clustered proteins form an organized matrix, such as the clathrin-coat, the interaction is described as a matricity.

<span class="mw-page-title-main">Complementarity-determining region</span> Part of the variable chains in immunoglobulins and T cell receptors

Complementarity-determining regions (CDRs) are polypeptide segments of the variable chains in immunoglobulins (antibodies) and T cell receptors, generated by B-cells and T-cells respectively. CDRs are where these molecules bind to their specific antigen and their structure/sequence determines the binding activity of the respective antibody. A set of CDRs constitutes a paratope, or the antigen-binding site. As the most variable parts of the molecules, CDRs are crucial to the diversity of antigen specificities generated by lymphocytes.

<span class="mw-page-title-main">Polyclonal B cell response</span> Immune response by adaptive immune system

Polyclonal B cell response is a natural mode of immune response exhibited by the adaptive immune system of mammals. It ensures that a single antigen is recognized and attacked through its overlapping parts, called epitopes, by multiple clones of B cell.

<span class="mw-page-title-main">Idiotype</span>

In immunology, an idiotype is a shared characteristic between a group of immunoglobulin or T-cell receptor (TCR) molecules based upon the antigen binding specificity and therefore structure of their variable region. The variable region of antigen receptors of T cells (TCRs) and B cells (immunoglobulins) contain complementarity-determining regions (CDRs) with unique amino acid sequences. They define the surface and properties of the variable region, determining the antigen specificity and therefore the idiotope of the molecule. Immunoglobulins or TCRs with a shared idiotope are the same idiotype. Antibody idiotype is determined by:

<span class="mw-page-title-main">Framework region</span>

In molecular biology, a framework region is a subdivision of the variable region (Fab) of the antibody. The variable region is composed of seven amino acid regions, four of which are framework regions and three of which are hypervariable regions. The framework region makes up about 85% of the variable region. Located on the tips of the Y-shaped molecule, the framework regions are responsible for acting as a scaffold for the complementarity determining regions (CDR), also referred to as hypervariable regions, of the Fab. These CDRs are in direct contact with the antigen and are involved in binding antigen, while the framework regions support the binding of the CDR to the antigen and aid in maintaining the overall structure of the four variable domains on the antibody. To increase its stability, the framework region has less variability in its amino acid sequences compared to the CDR.

<span class="mw-page-title-main">Glycan-protein interactions</span> Class of biological intermolecular interactions

Glycan-Protein interactions represent a class of biomolecular interactions that occur between free or protein-bound glycans and their cognate binding partners. Intramolecular glycan-protein (protein-glycan) interactions occur between glycans and proteins that they are covalently attached to. Together with protein-protein interactions, they form a mechanistic basis for many essential cell processes, especially for cell-cell interactions and host-cell interactions. For instance, SARS-CoV-2, the causative agent of COVID-19, employs its extensively glycosylated spike (S) protein to bind to the ACE2 receptor, allowing it to enter host cells. The spike protein is a trimeric structure, with each subunit containing 22 N-glycosylation sites, making it an attractive target for vaccine search.

References

  1. ↑ Goldberg, Richard J. (1952). "A Theory of Antibody—Antigen Reactions. I. Theory for Reactions of Multivalent Antigen with Bivalent and Univalent Antibody". Journal of the American Chemical Society. 74 (22): 5715–5725. doi:10.1021/ja01142a045.
  2. ↑ Sahimi, Muhammad (1994). Applications of Percolation Theory. London: CRC Press. p. 257. ISBN   978-0-203-22153-2.
  3. ↑ Spiers, JA (1958). "Goldberg's theory of antigen-antibody reactions in vitro". Immunology. 1 (2): 89–102. PMC   1423897 . PMID   13538526.
  4. 1 2 Janeway, Charles A Jr; Travers, Paul; Walport, Mark; Shlomchik, Mark J (2001). Immunobiology: The Immune System in Health and Disease (5 ed.). New York: Garland Science. ISBN   0-8153-3642-X.
  5. ↑ Sela-Culang, Inbal; Kunik, Vered; Ofran, Yanay (2013). "The structural basis of antibody-antigen recognition". Frontiers in Immunology. 4: 302. doi: 10.3389/fimmu.2013.00302 . PMC   3792396 . PMID   24115948.
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  27. ↑ Adams, Trudy; Osborn, Sancha; Rijpkema, Sjoerd (2005). "An immuno-diffusion assay to assess the protective antigen content of anthrax vaccine". Vaccine. 23 (36): 4517–4520. doi:10.1016/j.vaccine.2005.04.017. PMID   15908061.
  28. ↑ Lietze, Arthur (1969). "Quantitation of Food Adulterants by Multiple Radial Immunodiffusion. I. Cross-Reacting Antigen Mixtures". Journal of AOAC International. 52 (5): 988–995. doi: 10.1093/jaoac/52.5.988 .
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