An antibody, also known as an immunoglobulin, is a Y-shaped structure which consists of four polypeptides — two heavy chains and two light chains. This structure allows antibody molecules to carry out their dual functions: antigen binding and biological activity mediation.
Each function is carried out by different parts of the antibody: fragment antigen-binding (Fab fragment) and fragment crystallizable region (Fc region).
Fab fragment is a region on an antibody that binds to antigens. It is composed of one constant and one variable domain of each of the heavy and the light chain. These domains shape the paratope — the antigen-binding site — at the amino terminal end of the monomer.
Fc region is the tail region of an antibody that interacts with cell surface receptors called Fc receptors and some proteins of the complement system. This property allows antibodies to activate the immune system. The Fc regions of immunoglobulin Gs bear a highly conserved N-glycosylation site.
There are five immunoglobulin classes of antibody molecules found in serum: IgG, IgM, IgA, IgE and IgD. They are distinguished by the type of heavy chain they contain.
Immunoglobulin G (IgG) antibodies are large globular proteins with a molecular weight of about 150 kDa made of four peptide chains. It contains two identical γ (gamma) heavy chains of about 50 kDa and two identical light chains of about 25 kDa, thus a tetrameric quaternary structure.
IgG provides long term protection because it persists for months and years after the presence of the antigen that has triggered their production. IgG protects against bacteria, viruses, neutralises bacterial toxins, triggers complement protein systems and binds antigens to enhance the effectiveness of phagocytosis.
Immunoglobulin M (IgM) antibodies are constructed of five or six units (i.e. mostly as pentamers but also hexamers occur) which are each comprised of two heavy-chains (μ-chains) and two light chains, bound together by disulfide bonds and a so-called J-chain.
IgM is involved in the ABO blood group antigens on the surface of RBCs. IgM enhances ingestions of cells by phagocytosis.
Immunoglobulin A (IgA) antibodies consist of heavy (H) and light (L) chains. Each H chain is comprised of the constant region (Cα1, Cα2, Cα3), hinge region and the Variable (V) region. Light chains consist of the CL and Vκ or Vλ elements.
The main function of IgA is to bind antigens on microbes before they invade tissues. It aggregates the antigens and keeps them in the secretions so when the secretion is expelled, so is the antigen. IgA is also first defense for mucosal surfaces such as the intestines, nose, and lungs.
Immunoglobulin E (IgE) antibodies have only been found in mammals. IgE is synthesised by plasma cells. Monomers of IgE consist of two heavy chains (ε chain) and two light chains, with the ε chain containing 4 Ig-like constant domains (Cε1-Cε4).
IgE bind to mast cells and basophils which participate in the immune response. Some scientists think that IgE's purpose is to stop parasites.
Immunoglobulin D (IgD) antibodies are expressed in the plasma membranes of immature B-lymphocytes. IgD is also produced in a secreted form that is found in small amounts in blood serum. IgD plays a role in the induction of antibody production.
Table 1. Five types of antibodies and their functions
|Heavy chain||γ (gamma)||μ (mu)||α (alpha)||ε (epsilon)||δ (delta)|
|MW||150 kDa||900 kDa||385 kDa||200 kDa||180 kDa|
|Number of antigen binding sites||2||10||4||2||2|
|% of total antibody in serum||80%||6%||13%||0.002%||1%|
|Distribution||Intravascular and extravascular||Mainly intravascular||Intravascular and secretions||Basophils and mast cells (in saliva and nasal secretions)||Lymphocyte surface|
|Function||Main blood antibody, neutralizes toxins, opsonization||Primary response, fixes complement.
Monomer serves as B-cell receptor
|Secreted into mucus, tears and saliva||Antibody of allergy and anti-parasitic activity||B cell receptor|
Chimeric antibodies can be generated by fairly straightforward genetic engineering, by joining the immunoglobulin (Ig) variable regions of a selected mouse hybridoma to human Ig constant regions, and be used as such or as a first stage towards further humanization.
Anti-idotypic antibody is an antibody that binds to the idiotype of another antibody. An Idiotype (ID) actually consists of multiple antigenic determinants, each of which is an idiotope. The antigenic determinants or idiotopes can reside in the heavy chain component of the V region, in its light chain component, or they may consist of a surface made up of parts of both chains.
The bispecific antibody can override the specificity of an effector cell for its natural target and redirect it to kill a target that it would otherwise ignore. Different cytotoxic cells express different triggering molecules (receptors). Thus, by varying the specificities of target and effector binding domains a variety of effector responses can be directed against most types of target cells. Alternatively, the full range of effector functions (i.e. ADCC, phagocytosis, complement activation and extended serum half-life) can be conferred by targeting one binding specificity to serum immunoglobulin.
Recombinant antibodies are monoclonal antibodies produced by recombinant DNA technology. Owing to their high specificity, sensitivity and reproducibility, recombinant antibodies are widely used in biomedical science and medicine.
1. Janeway Jr, C. A., Travers, P., Walport, M., & Shlomchik, M. J. (2001). The structure of a typical antibody molecule. In Immunobiology: The Immune System in Health and Disease. 5th edition. Garland Science.
2. Chen, K., & Cerutti, A. (2011). The function and regulation of immunoglobulin D. Current opinion in immunology, 23(3), 345-352.
3. Solomon, A., & Weiss, D. T. (1995). Structural and functional properties of human lambda-light-chain variable-region subgroups. Clinical and diagnostic laboratory immunology, 2(4), 387.