Epitope

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. For example, the epitope is the specific piece of the antigen to which an antibody binds. 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 (as in the case of autoimmune diseases) are also epitopes.

The epitopes of protein antigens are divided into two categories, conformational epitopes and linear epitopes, based on their structure and interaction with the paratope.[1] A conformational epitope is composed of discontinuous sections of the antigen's amino acid sequence. These epitopes interact with the paratope based on the 3-D surface features and shape or tertiary structure of the antigen. The proportion of epitopes that are conformational is unknown.

By contrast, linear epitopes interact with the paratope based on their primary structure. A linear epitope is formed by a continuous sequence of amino acids from the antigen.

Function

T cell epitopes

T cell epitopes are presented on the surface of an antigen-presenting cell, where they are bound to MHC molecules. In humans, professional antigen-presenting cells are specialized to present MHC class II peptides, whereas most nucleated somatic cells present MHC class I peptides. T cell epitopes presented by MHC class I molecules are typically peptides between 8 and 11 amino acids in length, whereas MHC class II molecules present longer peptides, 13-17 amino acids in length,[2] and non-classical MHC molecules also present non-peptidic epitopes such as glycolipids.

Cross-activity

Epitopes are sometimes cross-reactive. This property is exploited by the immune system in regulation by anti-idiotypic antibodies (originally proposed by Nobel laureate Niels Kaj Jerne). If an antibody binds to an antigen's epitope, the paratope could become the epitope for another antibody that will then bind to it. If this second antibody is of IgM class, its binding can upregulate the immune response; if the second antibody is of IgG class, its binding can downregulate the immune response.

Epitope mapping

Epitopes can be mapped using protein microarrays, and with the ELISPOT or ELISA techniques. Another technique involves high-throughput mutagenesis, an epitope mapping strategy developed to improve rapid mapping of conformational epitopes on structurally complex proteins.[3]

MHC class I and II epitopes can be reliably predicted by computational means alone,[4] although not all in-silico T cell epitope prediction algorithms are equivalent in their accuracy.[5]

Epitope tags

Epitopes are often used in proteomics and the study of other gene products. Using recombinant DNA techniques genetic sequences coding for epitopes that are recognized by common antibodies can be fused to the gene. Following synthesis, the resulting epitope tag allows the antibody to find the protein or other gene product enabling lab techniques for localisation, purification, and further molecular characterisation. Common epitopes used for this purpose are Myc-tag, HA-tag, FLAG-tag, GST-tag, 6xHis[6] and OLLAS.[7] Peptides can also be bound by proteins that form covalent bonds to the peptide, allowing irreversible immobilisation[8] These strategies have also been successfully applied to the development of "epitope-focused" vaccine design.[9][10]

See also

References

  1. ↑ Huang, J.; Honda, W. (2006). "CED: a conformational epitope database". BMC Immunology. 7: 7. PMC 1513601 Freely accessible. PMID 16603068. doi:10.1186/1471-2172-7-7. Retrieved April 8, 2010.
  2. ↑ Alberts (2002). Molecular Biology of the Cell. New York: Garland Science. p. 1401.
  3. ↑ Davidson, Edgar; Doranz, Benjamin J. (2014). "A High-throughput Shotgun Mutagenesis Approach to Mapping B-cell Antibody Epitopes". Immunology. 143 (1): 13–20. PMC 4137951 Freely accessible. PMID 24854488. doi:10.1111/imm.12323.
  4. ↑ Koren, E.; AS De Groot (July 7, 2007). "Clinical validation of the "in silico" prediction of immunogenicity of a human recombinant therapeutic protein". Clinical Immunology. 124 (1): 26–32. doi:10.1016/j.clim.2007.03.544.
  5. ↑ De Groot, Anne; W. Martin (May 2009). "Reducing risk, improving outcomes: Bioengineering less immunogenic protein therapeutics". Clinical Immunology. 131 (2): 189–201. doi:10.1016/j.clim.2009.01.009.
  6. ↑ Walker, John; Ralph Rapley (2008). Molecular biomethods handbook. Humana Press. p. 467. ISBN 1-60327-374-3.
  7. ↑ Novus, Biologicals. "OLLAS Epitope Tag". Novus Biologicals. Retrieved 23 November 2011.
  8. ↑ Zakeri, B. (2012). "Peptide tag forming a rapid covalent bond to a protein, through engineering a bacterial adhesin". Proceedings of the National Academy of Sciences. 109 (12): E690–7. PMC 3311370 Freely accessible. PMID 22366317. doi:10.1073/pnas.1115485109.
  9. ↑ Correia, Bruno E.; Bates, John T.; Loomis, Rebecca J.; Baneyx, Gretchen; Carrico, Chris; Jardine, Joseph G.; Rupert, Peter; Correnti, Colin; Kalyuzhniy, Oleksandr (2014-03-13). "Proof of principle for epitope-focused vaccine design". Nature. 507 (7491): 201–206. ISSN 0028-0836. PMC 4260937 Freely accessible. PMID 24499818. doi:10.1038/nature12966.
  10. ↑ McBurney, Sean P.; Sunshine, Justine E.; Gabriel, Sarah; Huynh, Jeremy P.; Sutton, William F.; Fuller, Deborah H.; Haigwood, Nancy L.; Messer, William B. "Evaluation of protection induced by a dengue virus serotype 2 envelope domain III protein scaffold/DNA vaccine in non-human primates". Vaccine. 34: 3500–3507. PMC 4959041 Freely accessible. PMID 27085173. doi:10.1016/j.vaccine.2016.03.108.

Epitope prediction methods

Epitope databases

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