Epitope in Immunology Structure Types and Role

Let’s understand what is an epitope. In simple terms, an epitope is a site where antibodies bind to an antigen. However, to gain a better understanding of how everything fits together, it is useful to begin by examining the structure and function of an antibody. This is especially helpful when it comes to acquiring a better understanding of how personalized antibodies are developed.

When a foreign molecule is first detected by an organism's immune system, it is captured by a host of highly specialised cells. Dendritic cells are one such case. They are antigen-presenting cells that help decompose the foreign molecule into smaller parts and present these to B-cell lymphocytes as antigens.

After the antigen is introduced, a cellular mechanism called somatic hypermutation initiates the process of coding by the B cell lymphocyte of a new antibody. The antigen-binding site of the variable area of the antibody will be unique in order to bind specifically to an antigen-derived epitope.

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What is an Antigenic Determinant?

An antigenic determinant is the location of an antigen molecule which is called an epitope and interacts with the specific antigen-binding site within the variable area of an antibody molecule called paratope. The great fit between the epitope and the paratope is based on their three-dimensional interaction with the non-oval union. An antigenic or epitopic determinant may also react with a T-cell receiver for which it is specific.  An isolated antigen molecule may have multiple different epitopes available for response with antibody or T-cell receptors. There are two kinds of antigen determinants: conformational determinants as well as linear (sequential) determinants.

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Types of Epitope

Two kinds of epitopes are available - continuous and discontinuous 

Epitopes are involved in the reactivity of the epitope antibody (EAR).  B-cell epitopes are most often discontinuous (also known as conformational or assembled), consisting of segments of multiple chains joined together by bending the protein (antigen). Only about 10% of all epitopes identified by antibodies are considered continuous (also called linear or sequential). Complete protein networks usually detect the two types of epitopes of an antigen to a unique extent.  While the exact nature of a discontinuous epitope would normally be specified by sophisticated X-ray crystallography, peptides displayed on the microarrays are used experimentally to identify continuous epitopes. This is why much of the work on epitopes profiling focuses on continuous epitopes.

Antibodies Functions

Antibodies work directly and indirectly. For instance, viruses are usually deactivated by direct linkage. Pathogenic agents of a bacterial nature act more indirectly, binding to a protein on the surface of a bacterium. This acts as a signal to the entire immune system to move other cells forward to help eradicate the pathogen. From here onwards, it gets easier to control the same pathogen. B cells stay in the bloodstream and are ready to release antibodies against these specific antigens.

Epitope Structure

So, what is an Epitope Structure? An epitope is usually a protein segment that contains 5-6 amino acids. In this way, a complete protein will have a variety of epitopes where specific antibodies will bind. Linear amino acid sequences are referred to as continuous epithelial. Discontinuous epitopes are amino acid sequences, the conformation of which is bent. Distinguishing the two is an important factor in the production of customized antibodies.

It is important to note that a single antibody is produced by a B-cell lymphocyte, which recognizes and binds to a single epitope. Meanwhile, antibodies are released from B cells and travel through the bloodstream to help the immune system eradicate the alien molecule they were programmed to recognize.

Epitope Mapping

1. T Cell Epitopes

Class I and Class II epitopes of MHC can be reliably predicted by computerised means only, although not all T-in-silico cells' epitope prediction algorithms are equivalent in precision. There are two main ways to predict the peptide-MHC bond: based on data and structure. Structure-based methods model the peptide-MHC structure and require a lot of computing power. Data-based methods yield higher predictive returns than structure-based methods. Data-based methods predict peptide-MHC binding based on peptide sequences that bind MHC molecules. By identifying T lymphocyte epitopes, scientists can follow, phenotype and stimulate T lymphocytes.

2. B Cell Epitopes

There are two principal methods of cartography of epitopes: structural or functional studies. Methods used to structurally map epitopes include X-ray crystallography, nuclear magnetic resonance, and electronic microscopy. X-ray crystallography of Ag-Ab complexes is considered an accurate means of structural mapping of epitopes. Nuclear magnetic resonance may be used to map epitopes with Ag-Ab complex data. This method does not require crystals to form, but can only function on small peptides and proteins. Electron microscopy is a low-resolution method that localizes epitopes onto larger antigens such as viral particles.

Functional epitope mapping methods often use binding tests like western blot, dot blot, and/or ELISA to determine antibody binding. Competition methods seek to determine whether two monoclonal antibodies (mABs) can bind to one antigen at the same time or compete to bind at the same site. Another technology involves rapid mutagenesis, Mutagenesis uses randomized/localized mutations on individual remnants to map epitopes. Epitope mapping of B cells can be used to develop therapeutic antibodies, peptide-based vaccines and immuno-diagnostic tools. 

Substances that Act as Antigens

As far as infectious diseases are concerned, the following factors can act as antigens:

a. Microbial structures, including bacterial and fungal cell walls, protozoan cell membranes, bacterial and fungal capsules, microbial flagella, bacterial pills, viral capsids, glycoproteins related to viral envelopes, etc; and

b. Microbial toxins

Epitope-based Vaccines

The first epitopic vaccine was established in 1985 by Jacob et al. Epitopic vaccines stimulate both humoral and cellular immune responses with single-cell or T-cell epitopes. They may use more than one epitope to enhance their effectiveness. Silica mapping is frequently used to find epitopes for the vaccine. Once the candidate epitopes are identified, the structures are designed and tested for vaccine efficacy. Although epitope vaccines tend to be safe, a possible side effect is cytokine storms. 

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