Antibodies and their biological function
The role of antibodies in the immune system
Antibodies are central components in the body’s adaptive immune system. Their primary task is to identify and bind to infectious agents, so called pathogens, such as bacteria and viruses, and thereby support the body in neutralizing those to mitigate disease.
Once a pathogen enters the body, antibodies attach to specific surface molecules of the pathogen, called antigens. Through this attachment the harm of the pathogen can be reduced in two ways. Firstly, by the physical hindrance of the pathogen to interact with other parts of the body and thereby elicit its malicious effects. Secondly, the bound antibodies can trigger an immune response that in turn attracts other cell types with the purpose of neutralizing the foreign pathogen.
Structure of antibodies
Antibodies, also sometimes referred to as immunoglobulins, are large proteins (~150 kDa) with a characteristic structure often described as resembling the letter “Y”. Its stem, i.e. the lower part of the “Y”, is denoted the Fc region (crystallizable fragment) while the arms, i.e. upper part of the “Y”, are denoted as the Fab region (antigen binding fragment). The outermost part of each arm contains a so called paratope which binds the antigen, and the corresponding binding part of the antigen is called epitope. The interaction between the paratope and the epitope is highly specific, often described as a lock-and-key type of fit. See Figure 1.
Left) Schematic representation of the structure of an antibody. The stem of this “Y”-shaped protein is denoted as the Fc region (crystallizable fragment). The arms are denoted as the Fab region (antigen binding fragment).
Right) Illustration of how an antibody binds to an antigen on the surface of a pathogen. Looking at the molecular interaction in closer detail it is the outermost part of the Fab region, called the paratope, that binds to a part of the antigen called the epitope in a highly specific manner. Note that the images are not to scale.
Classification of antibodies – isotypes
The fact that antibodies within the immune system can recognize and interact with a plethora of pathogens in a highly specific manner implies that the paratope varies considerably between different antibodies. The Fc region however, is much less variable. As opposed to the Fab region, that interacts with the antigen, the Fc region instead interacts with the immune system and will signal to it which mechanism to employ to address the threat imposed by the pathogen recognized.
Depending on the structure of the Fc region an antibody is classified in different isotypes; those being IgA, IgD, IgE, IgG, and IgM. In human serum, IgG is the most abundant and accounts for ~70-85% of all the immunoglobulins.
Clonality of antibodies
From a biotechnical perspective, antibodies are often classified as either monoclonal or polyclonal. The terminology refers to the number of cell lines that have produced them. If it is only a single cell line the produced antibodies are identical and will collectively only be able to bind to a single epitope on the corresponding antigen. Monoclonals are produced in vitro in a laboratory setting. Polyclonals, on the other hand, are produced by multiple cell lines and are therefore collectively able to bind multiple epitopes on the corresponding antigen. Thereby, polyclonals could be seen as a heterogeneous mixture of monoclonals, and are often produced in a host animal (e.g. mouse, rabbit, goat or chicken). See Figure 2.
Left) Monoclonal antibodies are structurally identical and can therefore only bind a single epitope of the corresponding antigen.
Right) Polyclonal antibodies have structurally different paratopes and can therefore bind different epitopes of the corresponding antigen.