Epitope characteristics, types and functions

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Basil Manning

A epitope, also known as antigenic determinant, it is the specific binding site of the antigen or immunogen with the antibody or receptor of a cell of the immune system.

To understand this concept, it must be described that an immunogen is a macromolecule with the ability to induce an immune response, that is, it is an exogenous or endogenous substance that the body recognizes as a foreign or non-self substance, being capable of stimulating the activation of cells. B and T.

Antigen-antibody interaction. Marek M. Signs in Spanish by Alejandro Porto [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

In addition, it can bind to the generated immune system components. In the case of antigen, it also has antigenic determinants or epitopes capable of binding to antibodies and immune cells, but it does not generate an immune response..

The reality is that the immunogen fulfills the function of an antigen, but not every antigen behaves like an immunogen. However, despite these differences, as other authors do, the topic will continue using the term antigen as a synonym for immunogen..

Then, under this reflection it is described that the immune response will generate the formation of specific antibodies that will search for the antigen that originated them, to form an antigen-antibody complex, whose function is to neutralize or eliminate the antigen.

When the antibody finds the antigen, it binds to it in a specific way, like a key with its lock.

Article index

  • 1 Binding of epitope to paratope
  • 2 Recognition of epitopes by B and T cells
  • 3 Types of epitopes
  • 4 Epitopes in vaccine formation
  • 5 Epitopes as determinants of tumors
  • 6 Cryptic epitopes
  • 7 Reference

Binding of the epitope to the paratope

Epitope binding can occur with free antibodies or bound to an extracellular matrix.

The site of the antigen that contacts the antibody is called the epitope and the site of the antibody that binds to the epitope is called the paratope. The paratope is found at the tip of the variable region of the antibody and will be able to bind to a single epitope..

Another form of binding is when the antigen is processed by an antigen-presenting cell, and it exposes the antigenic determinants on its surface, which will bind to T and B cell receptors..

These aforementioned specific binding regions called epitope are formed by specific complex amino acid sequences, where the number of epitopes represents the valence of the antigen..

But not all antigenic determinants present induce an immune response. Therefore, the small subset of potential epitopes (TCE or BCE) present in an antigen capable of eliciting an immune response is known as immunodominance..

Recognition of epitopes by B and T cells

If the antigen is free, the epitopes have a spatial configuration, while if the antigen has been processed by an antigen-presenting cell, the exposed epitope will have another conformation, therefore several types can be distinguished..

B-cell-bound surface immunoglobulins and free antibodies recognize surface epitopes of antigens in their native three-dimensional form.

Whereas T cells recognize epitopes of antigens that have been processed by specialized cells (antigen presenting) that are coupled to molecules of the major histocompatibility complex.

Types of epitopes

-Continuous or linear epitopes: they are short sequences of contiguous amino acids of a protein.

-Discontinuous or conformational epitopes - Exists only when the protein folds into a particular conformation. These conformational epitopes are composed of amino acids that are not contiguous in the primary sequence, but that are brought into close proximity within the structure of the folded protein..

Epitopes in vaccine formation

Epitope-based vaccines will better manage desired and unwanted cross-reactivity.

T lymphocytes play an important role in the recognition and subsequent elimination of intracellular tumors and pathogens.

Induction of epitope-specific T cell responses may aid in the elimination of diseases for which there are no conventional vaccines..

Unfortunately, the lack of simple methods available to identify major T-cell epitopes, the high mutation rate of many pathogens, and the HLA polymorphism have hampered the development of effective T-cell epitope-based, or at least epitope-induced vaccines..

Currently, research has been carried out on bioinformatics tools together with certain experiments with T cells to identify epitopes of these cells processed naturally from various pathogens..

These techniques are believed to accelerate the development of next-generation T-cell epitope-based vaccines against various pathogens in the future..

Among the pathogens are some viruses, such as the Human Immunodeficiency Virus (HIV) and West Nile Virus (WNV), bacteria such as Mycobacterium tuberculosis and parasites such as Plasmodium.

Epitopes as determinants of tumors

It has been shown that tumors can induce immune responses, in fact some experiments carried out with chemically induced cancers have revealed an immune response against that tumor, but not against other tumors produced by the same carcinogen.

Meanwhile, tumors induced by oncogenic viruses behave differently, since on the surface of all neoplastic cells that have the virus genome there are processed viral peptides, in such a way that the T cells generated against a tumor will cross-react with all the others produced by the same virus.

On the other hand, numerous saccharide epitopes have been identified associated with tumor behavior and the regulation of the immune response, for which reason they are currently gaining interest due to their potential use in various aspects, such as therapeutic, prophylactic and diagnostic.

Cryptic epitopes

Antigen-presenting cells possess autoepitopes, generally in high concentration, bound to molecules of the major histocompatibility complex..

These have a very important function, since they are stimulators of the natural mechanisms for the elimination of self-reactive T cells, through a process called negative selection..

This process consists of detecting developing T cells capable of reacting against self antigens. Once these cells are identified, they are eliminated through a process of programmed cell death called apoptosis. This mechanism prevents autoimmune diseases.

However, self-epitopes that exist in very small amounts in an antigen-presenting cell are called cryptic, because they are unable to eliminate autoreactive T cells, allowing them to pass into the peripheral circulation and produce autoimmunity..

Reference

  1. El-Manzalawy Y, Dobbs D, Honavar V. Predicting flexible length linear B-cell epitopes. Comput Syst Bioinformatics Conf. 2008; 7: 121-32.
  2. Gorocica P, Atzín J, Saldaña A, Espinosa B, Urrea F, Alvarado N, Lascurain R. Tumor behavior and glycosylation. Rev Inst Nal Enf Resp Mex. 2008; 21 (4): 280-287
  3. Wikipedia contributors. Cryptic self epitopes. Wikipedia, The Free Encyclopedia. October 31, 2017, 11:30 UTC. Available at: https://en.wikipedia.org/
  4. Lanzavecchia A. How Can Cryptic Epitopes Trigger Autoimmunity?  J. Exp. Med. nineteen ninety five; 181 (1): 1945-1948
  5. Ivan Roitt. (2000) .Imunology Foundations. (9th Edition). Pan American. Madrid Spain.

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