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] Conformational and linear epitopes interact with the paratope based on the 3-D conformation adopted by the epitope, which is determined by the surface features of the involved epitope residues and the shape or tertiary structure of other segments of the antigen. A conformational epitope is formed by the 3-D conformation adopted by the interaction of discontiguous amino acid residues. In contrast, a linear epitope is formed by the 3-D conformation adopted by the interaction of contiguous amino acid residues. A linear epitope is not determined solely by the primary structure of the involved amino acids. Residues that flank such amino acid residues, as well as more distant amino acid residues of the antigen affect the ability of the primary structure residues to adopt the epitope's 3-D conformation.[2][3][4][5][6] The proportion of epitopes that are conformational is unknown.

Function

T cell epitopes[7]

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,[8] 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
Main article: 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.[9]

MHC class I and II epitopes can be reliably predicted by computational means alone,[10] although not all in-silico T cell epitope prediction algorithms are equivalent in their accuracy.[11]

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 characterization. Common epitopes used for this purpose are Myc-tag, HA-tag, FLAG-tag, GST-tag, 6xHis,[12] V5-tag and OLLAS.[13] Peptides can also be bound by proteins that form covalent bonds to the peptide, allowing irreversible immobilisation[14] These strategies have also been successfully applied to the development of "epitope-focused" vaccine design.[15][16]

Neoantigenic determinant

A neoantigenic determinant is an epitope on a neoantigen, which is a newly formed antigen that has not been previously recognized by the immune system.[17] Neoantigens are often associated with tumor antigens and are found in oncogenic cells.[18] Neoantigens and, by extension, neoantigenic determinants can be formed when a protein undergoes further modification within a biochemical pathway such as glycosylation, phosphorylation or proteolysis. This, by altering the structure of the protein, can produce new epitopes that are called neoantigenic determinants as they give rise to new antigenic determinants. Recognition requires separate, specific antibodies.

gollark: ddg! orbital laser strike
gollark: ...
gollark: ddg! deadly laser pointed at gnobody's eyes
gollark: Hmm. Troubling.
gollark: *Apparently* parsing things is somewhat hard. Ridiculous.

See also

References
  1. Huang, J.; Honda, W. (2006). "CED: a conformational epitope database". BMC Immunology. 7: 7. doi:10.1186/1471-2172-7-7. PMC 1513601. PMID 16603068.
  2. Anfinsen, C.B. (1973). "Principles That Govern The Folding Of Protein Chains". Science. 181 (4096): 223–230. Bibcode:1973Sci...181..223A. doi:10.1126/science.181.4096.223. PMID 4124164.
  3. Bergmann, C.C. (1994). "Differential Effects of Flanking Residues on Presentation of Epitopes from Chimeric Peptides". Journal of Virology. 68 (8): 5306–5310. doi:10.1128/JVI.68.8.5306-5310.1994. PMC 236480. PMID 7518534.
  4. Bergmann, C.C. (1996). "Flanking Residues Alter Antigenicity And Immunogenicity Of Multi-Unit CTL Epitopes". Journal of Immunology. 157 (8): 3242–3249. PMID 8871618.
  5. Briggs, S.S. (1993). "Fine Specificity of Antibody Recognition of Carcinoma-Associated Epithelial Mucins: Antibody Binding to Synthetic Peptide Epitopes". Eur. J. Cancer. 29A(2) (2): 230–237. doi:10.1016/0959-8049(93)90181-E. PMID 7678496.
  6. Craig, L. (1998). "The Role of Structure in Antibody Cross-reactivity Between Peptides and Folded Proteins". J. Mol. Biol. 281 (1): 183–201. doi:10.1006/jmbi.1998.1907. PMID 9680484.
  7. Steers, N.J. (2014). "Designing The Epitope Flanking Regions For Optimal Generation Of CTL Epitopes". Vaccine. 32 (28): 3509–3516. doi:10.1016/j.vaccine.2014.04.039. PMID 24795226.
  8. Alberts (2002). Molecular Biology of the Cell. New York: Garland Science. p. 1401.
  9. Davidson, Edgar; Doranz, Benjamin J. (2014). "A High-throughput Shotgun Mutagenesis Approach to Mapping B-cell Antibody Epitopes". Immunology. 143 (1): 13–20. doi:10.1111/imm.12323. PMC 4137951. PMID 24854488.
  10. 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. PMID 17490912.
  11. 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. PMID 19269256.
  12. Walker, John; Ralph Rapley (2008). Molecular bio-methods handbook. Humana Press. p. 467. ISBN 978-1-60327-374-9.
  13. Novus, Biologicals. "OLLAS Epitope Tag". Novus Biologicals. Retrieved 23 November 2011.
  14. 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. Bibcode:2012PNAS..109E.690Z. doi:10.1073/pnas.1115485109. PMC 3311370. PMID 22366317.
  15. 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. Bibcode:2014Natur.507..201C. doi:10.1038/nature12966. ISSN 0028-0836. PMC 4260937. PMID 24499818.
  16. McBurney, Sean P.; Sunshine, Justine E.; Gabriel, Sarah; Huynh, Jeremy P.; Sutton, William F.; Fuller, Deborah H.; Haigwood, Nancy L.; Messer, William B. (2016). "Evaluation of protection induced by a dengue virus serotype 2 envelope domain III protein scaffold/DNA vaccine in non-human primates". Vaccine. 34 (30): 3500–3507. doi:10.1016/j.vaccine.2016.03.108. PMC 4959041. PMID 27085173.
  17. Hans-Werner, Vohr (2005). Neoantigen-Forming Chemicals. Encyclopedic Reference of Immunotoxicology. p. 475. doi:10.1007/3-540-27806-0_1063. ISBN 978-3-540-44172-4.
  18. Neoantigen. (n.d.) Mosby's Medical Dictionary, 8th edition. (2009). Retrieved February 9, 2015 from Medical Dictionary Online

Epitope prediction methods
  • Epitopia: A web-server that predicts B-Cell Epitope using Naive Bayes approach on sequence or structure protein data.[1][2]
  • Saravanan, V; Gautham, N (2015). "Harnessing Computational Biology for Exact Linear B-Cell Epitope Prediction: A Novel Amino Acid Composition-Based Feature Descriptor". OMICS. 19: 648–58. doi:10.1089/omi.2015.0095. PMID 26406767.
  • Lbtope: Improved Method for Linear B-Cell Epitope Prediction Using Antigen’s Primary Sequence. PLoS ONE 8(5): e62216
  • BCEP: Prediction of B-cell epitopes using protein 3D structures.

Epitope databases
  1. Rubinstein, Nimrod D.; Mayrose, Itay; Martz, Eric; Pupko, Tal (2009-09-14). "Epitopia: a web-server for predicting B-cell epitopes". BMC Bioinformatics. 10: 287. doi:10.1186/1471-2105-10-287. ISSN 1471-2105. PMC 2751785. PMID 19751513.
  2. Rubinstein, Nimrod D.; Mayrose, Itay; Pupko, Tal (2009-02-01). "A machine-learning approach for predicting B-cell epitopes". Molecular Immunology. 46 (5): 840–847. doi:10.1016/j.molimm.2008.09.009. ISSN 0161-5890. PMID 18947876.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.