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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. 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.^[1]

The epitopes of protein antigens are divided into two categories, conformational epitopes and linear epitopes, based on their structure and interaction with the paratope.^[2] 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.^[3]^[4]^[5]^[6]^[7] 90% of epitopes are conformational.^[8]

Function

T cell epitopes

T cell epitopes^[9] are presented on the surface of an antigen-presenting cell, where they are bound to major histocompatibility complex (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,^[10] and non-classical MHC molecules also present non-peptidic epitopes such as glycolipids.

B cell epitopes

The part of the antigen that immunoglobulin or antibodies bind to is called a B-cell epitope.^[11] B cell epitopes can be divided into two groups: conformational or linear.^[11] B cell epitopes are mainly conformational.^[12]^[13] There are additional epitope types when the quaternary structure is considered.^[13] Epitopes that are masked when protein subunits aggregate are called cryptotopes.^[13] Neotopes are epitopes that are only recognized while in a specific quaternary structure and the residues of the epitope can span multiple protein subunits.^[13] Neotopes are not recognized once the subunits dissociate.^[13]

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.^{[citation needed]}

Epitope mapping

T cell epitopes

MHC class I and II epitopes can be reliably predicted by computational means alone,^[14] although not all in-silico T cell epitope prediction algorithms are equivalent in their accuracy.^[15] There are two main methods of predicting peptide-MHC binding: data-driven and structure-based.^[11] Structure based methods model the peptide-MHC structure and require great computational power.^[11] Data-driven methods have higher predictive performance than structure-based methods.^[11] Data-driven methods predict peptide-MHC binding based on peptide sequences that bind MHC molecules.^[11] By identifying T-cell epitopes, scientists can track, phenotype, and stimulate T-cells.^[16]^[17]^[18]^[19]

B cell epitopes

There are two main methods of epitope mapping: either structural or functional studies.^[20] Methods for structurally mapping epitopes include X-ray crystallography, nuclear magnetic resonance, and electron microscopy.^[20] X-ray crystallography of Ag-Ab complexes is considered an accurate way to structurally map epitopes.^[20] Nuclear magnetic resonance can be used to map epitopes by using data about the Ag-Ab complex.^[20] This method does not require crystal formation but can only work on small peptides and proteins.^[20] Electron microscopy is a low-resolution method that can localize epitopes on larger antigens like virus particles.^[20]

Methods for functionally mapping epitopes often use binding assays such as western blot, dot blot, and/or ELISA to determine antibody binding.^[20] Competition methods look to determine if two monoclonal antibodies (mABs) can bind to an antigen at the same time or compete with each other to bind at the same site.^[20] Another technique involves high-throughput mutagenesis, an epitope mapping strategy developed to improve rapid mapping of conformational epitopes on structurally complex proteins.^[21] Mutagenesis uses randomly/site-directed mutations at individual residues to map epitopes.^[20] B-cell epitope mapping can be used for the development of antibody therapeutics, peptide-based vaccines, and immunodiagnostic tools.^[20]^[22]

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,^[23] V5-tag and OLLAS.^[24] Peptides can also be bound by proteins that form covalent bonds to the peptide, allowing irreversible immobilisation.^[25] These strategies have also been successfully applied to the development of "epitope-focused" vaccine design.^[26]^[27]

Epitope-based vaccines

The first epitope-based vaccine was developed in 1985 by Jacob et al.^[28] Epitope-based vaccines stimulate humoral and cellular immune responses using isolated B-cell or T-cell epitopes.^[28]^[22]^[17] These vaccines can use multiple epitopes to increase their efficacy.^[28] To find epitopes to use for the vaccine, in silico mapping is often used.^[28] Once candidate epitopes are found, the constructs are engineered and tested for vaccine efficiency.^[28] While epitope-based vaccines are generally safe, one possible side effect is cytokine storms.^[28]

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.^[29] Neoantigens are often associated with tumor antigens and are found in oncogenic cells.^[30] 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.^{[citation needed]}

References

^ Mahmoudi Gomari, Mohammad; Saraygord-Afshari, Neda; Farsimadan, Marziye; Rostami, Neda; Aghamiri, Shahin; Farajollahi, Mohammad M. (1 December 2020). "Opportunities and challenges of the tag-assisted protein purification techniques: Applications in the pharmaceutical industry". Biotechnology Advances. 45: 107653. doi:10.1016/j.biotechadv.2020.107653. PMID 33157154. S2CID 226276355.
^ Huang J, Honda W (April 2006). "CED: a conformational epitope database". BMC Immunology. 7: 7. doi:10.1186/1471-2172-7-7. PMC 1513601. PMID 16603068.
^ Anfinsen CB (July 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.
^ Bergmann CC, Tong L, Cua R, Sensintaffar J, Stohlman S (August 1994). "Differential effects of flanking residues on presentation of epitopes from chimeric peptides". Journal of Virology. 68 (8): 5306–10. doi:10.1128/JVI.68.8.5306-5310.1994. PMC 236480. PMID 7518534.
^ Bergmann CC, Yao Q, Ho CK, Buckwold SL (October 1996). "Flanking residues alter antigenicity and immunogenicity of multi-unit CTL epitopes". Journal of Immunology. 157 (8): 3242–9. doi:10.4049/jimmunol.157.8.3242. PMID 8871618. S2CID 24717835.
^ Briggs S, Price MR, Tendler SJ (1993). "Fine specificity of antibody recognition of carcinoma-associated epithelial mucins: antibody binding to synthetic peptide epitopes". European Journal of Cancer. 29A (2): 230–7. doi:10.1016/0959-8049(93)90181-E. PMID 7678496.
^ Craig L, Sanschagrin PC, Rozek A, Lackie S, Kuhn LA, Scott JK (August 1998). "The role of structure in antibody cross-reactivity between peptides and folded proteins". Journal of Molecular Biology. 281 (1): 183–201. doi:10.1006/jmbi.1998.1907. PMID 9680484.
^ Ferdous, Saba; Kelm, Sebastian; Baker, Terry S.; Shi, Jiye; Martin, Andrew C. R. (1 October 2019). "B-cell epitopes: Discontinuity and conformational analysis". Molecular Immunology. 114: 643–650. doi:10.1016/j.molimm.2019.09.014. PMID 31546099. S2CID 202747810.
^ Steers NJ, Currier JR, Jobe O, Tovanabutra S, Ratto-Kim S, Marovich MA, et al. (June 2014). "Designing the epitope flanking regions for optimal generation of CTL epitopes". Vaccine. 32 (28): 3509–16. doi:10.1016/j.vaccine.2014.04.039. PMID 24795226.
^ Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002). Molecular biology of the cell (4th ed.). New York: Garland Science. p. 1401. ISBN 978-0-8153-3218-3.
^ ^a ^b ^c ^d ^e ^f Sanchez-Trincado, Jose L.; Gomez-Perosanz, Marta; Reche, Pedro A. (2017). "Fundamentals and Methods for T- and B-Cell Epitope Prediction". Journal of Immunology Research. 2017: 1–14. doi:10.1155/2017/2680160. PMC 5763123. PMID 29445754.
^ El-Manzalawy Y, Honavar V (November 2010). "Recent advances in B-cell epitope prediction methods". Immunome Research. 6 (Suppl 2): S2. doi:10.1186/1745-7580-6-S2-S2. PMC 2981878. PMID 21067544.
^ ^a ^b ^c ^d ^e Regenmortel, Marc H.V. (2009). "What is a B-Cell Epitope?". Epitope Mapping Protocols. Methods in Molecular Biology. Vol. 524. pp. 3–20. doi:10.1007/978-1-59745-450-6_1. ISBN 978-1-934115-17-6. PMID 19377933.
^ Koren, E.; Groot, Anne De; Jawa, V.; Beck, K.; Boone, T.; Rivera, D.; Li, L.; Mytych, D.; Koscec, M.; Weeraratne, D.; Swanson, S.; Martin, W. (1 January 2007). "Clinical validation of the 'in silico' prediction of immunogenicity of a human recombinant therapeutic protein". Institute for Immunology and Informatics Faculty Publications. 124 (1): 26–32. doi:10.1016/j.clim.2007.03.544. PMID 17490912. S2CID 12867280.
^ De Groot, Anne S.; Martin, William (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.
^ Peters, Bjoern; Nielsen, Morten; Sette, Alessandro (26 April 2020). "T Cell Epitope Predictions". Annual Review of Immunology. 38 (1): 123–145. doi:10.1146/annurev-immunol-082119-124838. PMC 10878398. PMID 32045313. S2CID 211085860.
^ ^a ^b Ahmad, Tarek A.; Eweida, Amrou E.; El-Sayed, Laila H. (December 2016). "T-cell epitope mapping for the design of powerful vaccines". Vaccine Reports. 6: 13–22. doi:10.1016/j.vacrep.2016.07.002.
^ Dezfulian MH, Kula T, Pranzatelli T, Kamitaki N, Meng Q, Khatri B, Perez P, Xu Q, Chang A, Kohlgruber AC, Leng Y, Jupudi AA, Joachims ML, Chiorini JA, Lessard CJ, Farris AD, Muthuswamy SK, Warner BM, Elledge SJ (December 2023). "TScan-II: A genome-scale platform for the de novo identification of CD4+ T cell epitopes". Cell. 186 (25): 5569–86. doi:10.1016/j.cell.2023.10.024. PMID 38016469.
^ Kula T, Dezfulian MH, Wang CI, Abdelfattah NS, Hartman ZC, Wucherpfennig KW, Lyerly HK, Elledge SJ (August 2019). "T-Scan: A Genome-wide Method for the Systematic Discovery of T Cell Epitopes". Cell. 178 (4): 1016–28. doi:10.1016/j.cell.2019.07.009. PMC 6939866. PMID 31398327.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j Potocnakova, Lenka; Bhide, Mangesh; Pulzova, Lucia Borszekova (2016). "An Introduction to B-Cell Epitope Mapping and In Silico Epitope Prediction". Journal of Immunology Research. 2016: 1–11. doi:10.1155/2016/6760830. PMC 5227168. PMID 28127568.
^ Davidson, Edgar; Doranz, Benjamin J. (September 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.
^ ^a ^b Ahmad, Tarek A.; Eweida, Amrou E.; Sheweita, Salah A. (2016). "B-cell epitope mapping for the design of vaccines and effective diagnostics". Trials in Vaccinology. 5: 71–83. doi:10.1016/j.trivac.2016.04.003.
^ Park HR, Cockrell LM, Du Y, Kasinski A, Havel J, Zhao J, Reyes-Turcu F, Wilkinson KD, Fu H (2008). "Protein–Protein Interactions". In Walker J, Rapley R (eds.). Molecular bio-methods handbook (2nd ed.). Humana Press. pp. 463–494, See p. 467. doi:10.1007/978-1-60327-375-6. ISBN 978-1-60327-374-9.
^ Novus, Biologicals. "OLLAS Epitope Tag". Novus Biologicals. Retrieved 23 November 2011.
^ Zakeri B, Fierer JO, Celik E, Chittock EC, Schwarz-Linek U, Moy VT, Howarth M (March 2012). "Peptide tag forming a rapid covalent bond to a protein, through engineering a bacterial adhesin". Proceedings of the National Academy of Sciences of the United States of America. 109 (12): E690–7. Bibcode:2012PNAS..109E.690Z. doi:10.1073/pnas.1115485109. PMC 3311370. PMID 22366317.
^ Correia BE, Bates JT, Loomis RJ, Baneyx G, Carrico C, Jardine JG, et al. (March 2014). "Proof of principle for epitope-focused vaccine design". Nature. 507 (7491): 201–6. Bibcode:2014Natur.507..201C. doi:10.1038/nature12966. PMC 4260937. PMID 24499818.
^ McBurney SP, Sunshine JE, Gabriel S, Huynh JP, Sutton WF, Fuller DH, et al. (June 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): 3500–7. doi:10.1016/j.vaccine.2016.03.108. PMC 4959041. PMID 27085173.
^ ^a ^b ^c ^d ^e ^f Parvizpour, Sepideh; Pourseif, Mohammad M.; Razmara, Jafar; Rafi, Mohammad A.; Omidi, Yadollah (June 2020). "Epitope-based vaccine design: a comprehensive overview of bioinformatics approaches". Drug Discovery Today. 25 (6): 1034–42. doi:10.1016/j.drudis.2020.03.006. PMID 32205198. S2CID 214629963.
^ Hans-Werner V (2005). "Neoantigen-Forming Chemicals". Encyclopedic Reference of Immunotoxicology. p. 475. doi:10.1007/3-540-27806-0_1063. ISBN 978-3540441724.
^ Neoantigen. (n.d.) Mosby's Medical Dictionary, 8th edition. (2009). Retrieved February 9, 2015 from Medical Dictionary Online

External links

Epitope prediction methods

Rubinstein ND, Mayrose I, Martz E, Pupko T (September 2009). "Epitopia: a web-server for predicting B-cell epitopes". BMC Bioinformatics. 10: 287. doi:10.1186/1471-2105-10-287. PMC 2751785. PMID 19751513.
Rubinstein ND, Mayrose I, Pupko T (February 2009). "A machine-learning approach for predicting B-cell epitopes". Molecular Immunology. 46 (5): 840–7. doi:10.1016/j.molimm.2008.09.009. PMID 18947876.
Saravanan V, Gautham N (October 2015). "Harnessing Computational Biology for Exact Linear B-Cell Epitope Prediction: A Novel Amino Acid Composition-Based Feature Descriptor". Omics. 19 (10): 648–658. doi:10.1089/omi.2015.0095. PMID 26406767.
Singh H, Ansari HR, Raghava GP (2013). "Improved method for linear B-cell epitope prediction using antigen's primary sequence". PLOS ONE. 8 (5): e62216. Bibcode:2013PLoSO...862216S. doi:10.1371/journal.pone.0062216. PMC 3646881. PMID 23667458.

Epitope databases

[1] Mahmoudi Gomari, Mohammad; Saraygord-Afshari, Neda; Farsimadan, Marziye; Rostami, Neda; Aghamiri, Shahin; Farajollahi, Mohammad M. (1 December 2020). "Opportunities and challenges of the tag-assisted protein purification techniques: Applications in the pharmaceutical industry". Biotechnology Advances. 45: 107653. doi:10.1016/j.biotechadv.2020.107653. PMID 33157154. S2CID 226276355.

[2] Huang J, Honda W (April 2006). "CED: a conformational epitope database". BMC Immunology. 7: 7. doi:10.1186/1471-2172-7-7. PMC 1513601. PMID 16603068.

[3] Anfinsen CB (July 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.

[4] Bergmann CC, Tong L, Cua R, Sensintaffar J, Stohlman S (August 1994). "Differential effects of flanking residues on presentation of epitopes from chimeric peptides". Journal of Virology. 68 (8): 5306–10. doi:10.1128/JVI.68.8.5306-5310.1994. PMC 236480. PMID 7518534.

[5] Bergmann CC, Yao Q, Ho CK, Buckwold SL (October 1996). "Flanking residues alter antigenicity and immunogenicity of multi-unit CTL epitopes". Journal of Immunology. 157 (8): 3242–9. doi:10.4049/jimmunol.157.8.3242. PMID 8871618. S2CID 24717835.

[6] Briggs S, Price MR, Tendler SJ (1993). "Fine specificity of antibody recognition of carcinoma-associated epithelial mucins: antibody binding to synthetic peptide epitopes". European Journal of Cancer. 29A (2): 230–7. doi:10.1016/0959-8049(93)90181-E. PMID 7678496.

[7] Craig L, Sanschagrin PC, Rozek A, Lackie S, Kuhn LA, Scott JK (August 1998). "The role of structure in antibody cross-reactivity between peptides and folded proteins". Journal of Molecular Biology. 281 (1): 183–201. doi:10.1006/jmbi.1998.1907. PMID 9680484.

[8] Ferdous, Saba; Kelm, Sebastian; Baker, Terry S.; Shi, Jiye; Martin, Andrew C. R. (1 October 2019). "B-cell epitopes: Discontinuity and conformational analysis". Molecular Immunology. 114: 643–650. doi:10.1016/j.molimm.2019.09.014. PMID 31546099. S2CID 202747810.

[9] Steers NJ, Currier JR, Jobe O, Tovanabutra S, Ratto-Kim S, Marovich MA, et al. (June 2014). "Designing the epitope flanking regions for optimal generation of CTL epitopes". Vaccine. 32 (28): 3509–16. doi:10.1016/j.vaccine.2014.04.039. PMID 24795226.

[10] Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002). Molecular biology of the cell (4th ed.). New York: Garland Science. p. 1401. ISBN 978-0-8153-3218-3.

[Sanchez-Trincado_et_al_2017-11] ^ ^a ^b ^c ^d ^e ^f Sanchez-Trincado, Jose L.; Gomez-Perosanz, Marta; Reche, Pedro A. (2017). "Fundamentals and Methods for T- and B-Cell Epitope Prediction". Journal of Immunology Research. 2017: 1–14. doi:10.1155/2017/2680160. PMC 5763123. PMID 29445754.

[12] El-Manzalawy Y, Honavar V (November 2010). "Recent advances in B-cell epitope prediction methods". Immunome Research. 6 (Suppl 2): S2. doi:10.1186/1745-7580-6-S2-S2. PMC 2981878. PMID 21067544.

[Regenmortel2009-13] Regenmortel, Marc H.V. (2009). "What is a B-Cell Epitope?". Epitope Mapping Protocols. Methods in Molecular Biology. Vol. 524. pp. 3–20. doi:10.1007/978-1-59745-450-6_1. ISBN 978-1-934115-17-6. PMID 19377933.

[14] Koren, E.; Groot, Anne De; Jawa, V.; Beck, K.; Boone, T.; Rivera, D.; Li, L.; Mytych, D.; Koscec, M.; Weeraratne, D.; Swanson, S.; Martin, W. (1 January 2007). "Clinical validation of the 'in silico' prediction of immunogenicity of a human recombinant therapeutic protein". Institute for Immunology and Informatics Faculty Publications. 124 (1): 26–32. doi:10.1016/j.clim.2007.03.544. PMID 17490912. S2CID 12867280.

[15] De Groot, Anne S.; Martin, William (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.

[16] Peters, Bjoern; Nielsen, Morten; Sette, Alessandro (26 April 2020). "T Cell Epitope Predictions". Annual Review of Immunology. 38 (1): 123–145. doi:10.1146/annurev-immunol-082119-124838. PMC 10878398. PMID 32045313. S2CID 211085860.

[Ahmad_Eweida_El-Sayed_2016-17] Ahmad, Tarek A.; Eweida, Amrou E.; El-Sayed, Laila H. (December 2016). "T-cell epitope mapping for the design of powerful vaccines". Vaccine Reports. 6: 13–22. doi:10.1016/j.vacrep.2016.07.002.

[18] Dezfulian MH, Kula T, Pranzatelli T, Kamitaki N, Meng Q, Khatri B, Perez P, Xu Q, Chang A, Kohlgruber AC, Leng Y, Jupudi AA, Joachims ML, Chiorini JA, Lessard CJ, Farris AD, Muthuswamy SK, Warner BM, Elledge SJ (December 2023). "TScan-II: A genome-scale platform for the de novo identification of CD4+ T cell epitopes". Cell. 186 (25): 5569–86. doi:10.1016/j.cell.2023.10.024. PMID 38016469.

[19] Kula T, Dezfulian MH, Wang CI, Abdelfattah NS, Hartman ZC, Wucherpfennig KW, Lyerly HK, Elledge SJ (August 2019). "T-Scan: A Genome-wide Method for the Systematic Discovery of T Cell Epitopes". Cell. 178 (4): 1016–28. doi:10.1016/j.cell.2019.07.009. PMC 6939866. PMID 31398327.

[Potocnakova_et_al_2016-20] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j Potocnakova, Lenka; Bhide, Mangesh; Pulzova, Lucia Borszekova (2016). "An Introduction to B-Cell Epitope Mapping and In Silico Epitope Prediction". Journal of Immunology Research. 2016: 1–11. doi:10.1155/2016/6760830. PMC 5227168. PMID 28127568.

[21] Davidson, Edgar; Doranz, Benjamin J. (September 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.

[Ahmad_Eweida_Sheweita_2016-22] Ahmad, Tarek A.; Eweida, Amrou E.; Sheweita, Salah A. (2016). "B-cell epitope mapping for the design of vaccines and effective diagnostics". Trials in Vaccinology. 5: 71–83. doi:10.1016/j.trivac.2016.04.003.

[23] Park HR, Cockrell LM, Du Y, Kasinski A, Havel J, Zhao J, Reyes-Turcu F, Wilkinson KD, Fu H (2008). "Protein–Protein Interactions". In Walker J, Rapley R (eds.). Molecular bio-methods handbook (2nd ed.). Humana Press. pp. 463–494, See p. 467. doi:10.1007/978-1-60327-375-6. ISBN 978-1-60327-374-9.

[24] Novus, Biologicals. "OLLAS Epitope Tag". Novus Biologicals. Retrieved 23 November 2011.

[25] Zakeri B, Fierer JO, Celik E, Chittock EC, Schwarz-Linek U, Moy VT, Howarth M (March 2012). "Peptide tag forming a rapid covalent bond to a protein, through engineering a bacterial adhesin". Proceedings of the National Academy of Sciences of the United States of America. 109 (12): E690–7. Bibcode:2012PNAS..109E.690Z. doi:10.1073/pnas.1115485109. PMC 3311370. PMID 22366317.

[26] Correia BE, Bates JT, Loomis RJ, Baneyx G, Carrico C, Jardine JG, et al. (March 2014). "Proof of principle for epitope-focused vaccine design". Nature. 507 (7491): 201–6. Bibcode:2014Natur.507..201C. doi:10.1038/nature12966. PMC 4260937. PMID 24499818.

[27] McBurney SP, Sunshine JE, Gabriel S, Huynh JP, Sutton WF, Fuller DH, et al. (June 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): 3500–7. doi:10.1016/j.vaccine.2016.03.108. PMC 4959041. PMID 27085173.

[Parvizpour_et_al_2020-28] ^ ^a ^b ^c ^d ^e ^f Parvizpour, Sepideh; Pourseif, Mohammad M.; Razmara, Jafar; Rafi, Mohammad A.; Omidi, Yadollah (June 2020). "Epitope-based vaccine design: a comprehensive overview of bioinformatics approaches". Drug Discovery Today. 25 (6): 1034–42. doi:10.1016/j.drudis.2020.03.006. PMID 32205198. S2CID 214629963.

[29] Hans-Werner V (2005). "Neoantigen-Forming Chemicals". Encyclopedic Reference of Immunotoxicology. p. 475. doi:10.1007/3-540-27806-0_1063. ISBN 978-3540441724.

[30] Neoantigen. (n.d.) Mosby's Medical Dictionary, 8th edition. (2009). Retrieved February 9, 2015 from Medical Dictionary Online

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+{{Short description|Chemical entity which can be bound by an antibody}}
-An '''epitope''', also known as '''antigenic determinant''', is the part of an [[antigen]] that is recognized by the [[immune system]], specifically by [[antibody|antibodies]], [[B cell]]s, or [[T cell]]s. 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 [[exogenous antigen|non-self proteins]], sequences derived from the host that can be recognized (as in the case of autoimmune diseases) are also epitopes.
+An '''epitope''', also known as '''antigenic determinant''', is the part of an [[antigen]] that is recognized by the [[immune system]], specifically by [[antibody|antibodies]], [[B cell]]s, or [[T cell]]s. The part of an antibody that binds to the epitope is called a [[paratope]]. Although epitopes are usually [[exogenous antigen|non-self proteins]], sequences derived from the host that can be recognized (as in the case of autoimmune diseases) are also epitopes.<ref>{{cite journal |last1=Mahmoudi Gomari |first1=Mohammad |last2=Saraygord-Afshari |first2=Neda |last3=Farsimadan |first3=Marziye |last4=Rostami |first4=Neda |last5=Aghamiri |first5=Shahin |last6=Farajollahi |first6=Mohammad M. |title=Opportunities and challenges of the tag-assisted protein purification techniques: Applications in the pharmaceutical industry |journal=Biotechnology Advances |date=1 December 2020 |volume=45 |pages=107653 |doi=10.1016/j.biotechadv.2020.107653 |pmid=33157154 |s2cid=226276355 }}</ref>
-The epitopes of [[protein]] antigens are divided into two categories, [[conformational epitope]]s and [[linear epitope]]s, based on their structure and interaction with the paratope.<ref>{{cite journal | vauthors = Huang J, Honda W | title = CED: a conformational epitope database | journal = BMC Immunology | volume = 7 | pages = 7 | date = April 2006 | pmid = 16603068 | pmc = 1513601 | doi = 10.1186/1471-2172-7-7 }}</ref>   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.<ref>{{cite journal | vauthors = Anfinsen CB | title = Principles that govern the folding of protein chains | journal = Science | volume = 181 | issue = 4096 | pages = 223–30 | date = July 1973 | pmid = 4124164 | doi = 10.1126/science.181.4096.223 | bibcode = 1973Sci...181..223A }}</ref><ref>{{cite journal | vauthors = Bergmann CC, Tong L, Cua R, Sensintaffar J, Stohlman S | title = Differential effects of flanking residues on presentation of epitopes from chimeric peptides | journal = Journal of Virology | volume = 68 | issue = 8 | pages = 5306–10 | date = August 1994 | pmid = 7518534 | pmc = 236480 | doi = 10.1128/JVI.68.8.5306-5310.1994 }}</ref><ref>{{cite journal | vauthors = Bergmann CC, Yao Q, Ho CK, Buckwold SL | title = Flanking residues alter antigenicity and immunogenicity of multi-unit CTL epitopes | journal = Journal of Immunology | volume = 157 | issue = 8 | pages = 3242–9 | date = October 1996 | pmid = 8871618 }}</ref><ref>{{cite journal | vauthors = Briggs S, Price MR, Tendler SJ | title = Fine specificity of antibody recognition of carcinoma-associated epithelial mucins: antibody binding to synthetic peptide epitopes | journal = European Journal of Cancer | volume = 29A | issue = 2 | pages = 230–7 | date = 1993 | pmid = 7678496 | doi = 10.1016/0959-8049(93)90181-E }}</ref><ref>{{cite journal | vauthors = Craig L, Sanschagrin PC, Rozek A, Lackie S, Kuhn LA, Scott JK | title = The role of structure in antibody cross-reactivity between peptides and folded proteins | journal = Journal of Molecular Biology | volume = 281 | issue = 1 | pages = 183–201 | date = August 1998 | pmid = 9680484 | doi = 10.1006/jmbi.1998.1907 }}</ref>  The proportion of epitopes that are conformational is unknown.{{citation needed|date=September 2012}}
+The epitopes of [[protein]] antigens are divided into two categories, [[conformational epitope]]s and [[linear epitope]]s, based on their structure and interaction with the paratope.<ref>{{cite journal | vauthors = Huang J, Honda W | title = CED: a conformational epitope database | journal = BMC Immunology | volume = 7 | pages = 7 | date = April 2006 | pmid = 16603068 | pmc = 1513601 | doi = 10.1186/1471-2172-7-7 | doi-access = free }}</ref>   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.<ref>{{cite journal | vauthors = Anfinsen CB | title = Principles that govern the folding of protein chains | journal = Science | volume = 181 | issue = 4096 | pages = 223–230 | date = July 1973 | pmid = 4124164 | doi = 10.1126/science.181.4096.223 | bibcode = 1973Sci...181..223A }}</ref><ref>{{cite journal | vauthors = Bergmann CC, Tong L, Cua R, Sensintaffar J, Stohlman S | title = Differential effects of flanking residues on presentation of epitopes from chimeric peptides | journal = Journal of Virology | volume = 68 | issue = 8 | pages = 5306–10 | date = August 1994 | pmid = 7518534 | pmc = 236480 | doi = 10.1128/JVI.68.8.5306-5310.1994 }}</ref><ref>{{cite journal | vauthors = Bergmann CC, Yao Q, Ho CK, Buckwold SL | title = Flanking residues alter antigenicity and immunogenicity of multi-unit CTL epitopes | journal = Journal of Immunology | volume = 157 | issue = 8 | pages = 3242–9 | date = October 1996 | doi = 10.4049/jimmunol.157.8.3242 | pmid = 8871618 | s2cid = 24717835 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Briggs S, Price MR, Tendler SJ | title = Fine specificity of antibody recognition of carcinoma-associated epithelial mucins: antibody binding to synthetic peptide epitopes | journal = European Journal of Cancer | volume = 29A | issue = 2 | pages = 230–7 | date = 1993 | pmid = 7678496 | doi = 10.1016/0959-8049(93)90181-E }}</ref><ref>{{cite journal | vauthors = Craig L, Sanschagrin PC, Rozek A, Lackie S, Kuhn LA, Scott JK | title = The role of structure in antibody cross-reactivity between peptides and folded proteins | journal = Journal of Molecular Biology | volume = 281 | issue = 1 | pages = 183–201 | date = August 1998 | pmid = 9680484 | doi = 10.1006/jmbi.1998.1907 }}</ref>  90% of epitopes are conformational.<ref>{{cite journal |last1=Ferdous |first1=Saba |last2=Kelm |first2=Sebastian |last3=Baker |first3=Terry S. |last4=Shi |first4=Jiye |last5=Martin |first5=Andrew C. R. |title=B-cell epitopes: Discontinuity and conformational analysis |journal=Molecular Immunology |date=1 October 2019 |volume=114 |pages=643–650 |doi=10.1016/j.molimm.2019.09.014 |pmid=31546099 |s2cid=202747810 |url=https://discovery.ucl.ac.uk/id/eprint/10081794/ }}</ref>
 ==Function==
 === T cell epitopes ===
-[[T cell]] epitopes<ref>{{cite journal | vauthors = Steers NJ, Currier JR, Jobe O, Tovanabutra S, Ratto-Kim S, Marovich MA, Kim JH, Michael NL, Alving CR, Rao M | display-authors = 6 | title = Designing the epitope flanking regions for optimal generation of CTL epitopes | journal = Vaccine | volume = 32 | issue = 28 | pages = 3509–16 | date = June 2014 | pmid = 24795226 | doi = 10.1016/j.vaccine.2014.04.039 }}</ref> are presented on the surface of an [[antigen-presenting cell]], where they are bound to [[major histocompatibility complex|MHC]] molecules. In humans, professional antigen-presenting cells are specialized to present [[MHC class II]] peptides, whereas most nucleated [[somatic cell]]s 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,<ref>{{cite book | vauthors = Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P |title=Molecular biology of the cell |date=2002 |publisher=Garland Science |location=New York |isbn=978-0-8153-3218-3 |edition=4th |page=1401 }}</ref> and non-classical MHC molecules also present non-peptidic epitopes such as [[glycolipid]]s.
+[[T cell]] epitopes<ref>{{cite journal | vauthors = Steers NJ, Currier JR, Jobe O, Tovanabutra S, Ratto-Kim S, Marovich MA, Kim JH, Michael NL, Alving CR, Rao M | display-authors = 6 | title = Designing the epitope flanking regions for optimal generation of CTL epitopes | journal = Vaccine | volume = 32 | issue = 28 | pages = 3509–16 | date = June 2014 | pmid = 24795226 | doi = 10.1016/j.vaccine.2014.04.039 }}</ref> are presented on the surface of an [[antigen-presenting cell]], where they are bound to [[major histocompatibility complex]] (MHC) molecules. In humans, [[Antigen-presenting cell#Professional APCs|professional antigen-presenting cell]]s are specialized to present [[MHC class II]] peptides, whereas most nucleated [[somatic cell]]s 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,<ref>{{cite book | vauthors = Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P |title=Molecular biology of the cell |date=2002 |publisher=Garland Science |location=New York |isbn=978-0-8153-3218-3 |edition=4th |page=1401 }}</ref> and non-classical MHC molecules also present non-peptidic epitopes such as [[glycolipid]]s.
 === B cell epitopes ===
-The part of the antigen that immunoglobulin or antibodies bind to is called a B-cell epitope.<ref name=":0">{{cite journal | vauthors = Sanchez-Trincado JL, Gomez-Perosanz M, Reche PA | title = Fundamentals and Methods for T- and B-Cell Epitope Prediction | journal = Journal of Immunology Research | volume = 2017 | pages = 2680160 | date = 2017-12-28 | pmid = 29445754 | pmc = 5763123 | doi = 10.1155/2017/2680160 }}</ref> Similar to T cell epitopes, B cell epitopes can be divided into two groups: conformational or linear.<ref name=":0" /> B cell epitopes are mainly conformational.<ref>{{cite journal | vauthors = El-Manzalawy Y, Honavar V | title = Recent advances in B-cell epitope prediction methods | journal = Immunome Research | volume = 6 Suppl 2 | issue = Suppl 2 | pages = S2 | date = November 2010 | pmid = 21067544 | pmc = 2981878 | doi = 10.1186/1745-7580-6-S2-S2 }}</ref><ref name=":1">{{Cite book |title=Epitope Mapping Protocols|date=2009|publisher=Humana Press|isbn=978-1-934115-17-6| veditors = Schutkowski M, Reineke U |series=Methods in Molecular Biology™|volume=524|location=Totowa, NJ|doi=10.1007/978-1-59745-450-6|s2cid=29203458}}</ref> There are additional epitope types when the quaternary structure is considered.<ref name=":1" /> Epitopes that are masked when protein subunits aggregate are called cryptotopes.<ref name=":1" /> Neotopes are epitopes that are only recognized while in a specific quaternary structure and the residues of the epitope can span multiple protein subunits.<ref name=":1" /> Neotopes are not recognized once the subunits dissociate.<ref name=":1" />
+The part of the antigen that immunoglobulin or antibodies bind to is called a B-cell epitope.<ref name="Sanchez-Trincado et al 2017">{{cite journal |last1=Sanchez-Trincado |first1=Jose L. |last2=Gomez-Perosanz |first2=Marta |last3=Reche |first3=Pedro A. |title=Fundamentals and Methods for T- and B-Cell Epitope Prediction |journal=Journal of Immunology Research |date=2017 |volume=2017 |pages=1–14 |doi=10.1155/2017/2680160 |pmid=29445754 |pmc=5763123 |doi-access=free }}</ref> B cell epitopes can be divided into two groups: conformational or linear.<ref name="Sanchez-Trincado et al 2017"/> B cell epitopes are mainly conformational.<ref>{{cite journal | vauthors = El-Manzalawy Y, Honavar V | title = Recent advances in B-cell epitope prediction methods | journal = Immunome Research | volume = 6 | issue = Suppl 2 | pages = S2 | date = November 2010 | pmid = 21067544 | pmc = 2981878 | doi = 10.1186/1745-7580-6-S2-S2 | doi-access = free }}</ref><ref name=Regenmortel2009>{{cite book |doi=10.1007/978-1-59745-450-6_1 |chapter=What is a B-Cell Epitope? |title=Epitope Mapping Protocols |series=Methods in Molecular Biology |year=2009 |last1=Regenmortel |first1=Marc H.V. |volume=524 |pages=3–20 |pmid=19377933 |isbn=978-1-934115-17-6 }}</ref> There are additional epitope types when the quaternary structure is considered.<ref name=Regenmortel2009/> Epitopes that are masked when protein subunits aggregate are called [[cryptotope]]s.<ref name=Regenmortel2009/> Neotopes are epitopes that are only recognized while in a specific quaternary structure and the residues of the epitope can span multiple protein subunits.<ref name=Regenmortel2009/> Neotopes are not recognized once the subunits dissociate.<ref name=Regenmortel2009/>
 ===Cross-activity===
@@ Line 18: / Line 19: @@
 === T cell epitopes ===
-MHC class I and II epitopes can be reliably predicted by computational means alone,<ref>{{cite journal | vauthors = Koren E, De Groot AS, Jawa V, Beck KD, Boone T, Rivera D, Li L, Mytych D, Koscec M, Weeraratne D, Swanson S, Martin W | display-authors = 6 | title = Clinical validation of the "in silico" prediction of immunogenicity of a human recombinant therapeutic protein | journal = Clinical Immunology | volume = 124 | issue = 1 | pages = 26–32 | date = July 2007 | pmid = 17490912 | doi = 10.1016/j.clim.2007.03.544 }}</ref> although not all in-silico T cell epitope prediction algorithms are equivalent in their accuracy.<ref>{{cite journal | vauthors = De Groot AS, Martin W | title = Reducing risk, improving outcomes: bioengineering less immunogenic protein therapeutics | journal = Clinical Immunology | volume = 131 | issue = 2 | pages = 189–201 | date = May 2009 | pmid = 19269256 | doi = 10.1016/j.clim.2009.01.009 }}</ref> There are two main methods of predicting peptide-MHC binding: data-driven and structure-based.<ref name=":0" /> Structure based methods model the peptide-MHC structure and require great computational power.<ref name=":0" /> Data-driven methods have higher predictive performance than structure-based methods.<ref name=":0" /> Data-driven methods predict peptide-MHC binding based on peptide sequences that bind MHC molecules.<ref name=":0" /> By identifying T-cell epitopes, scientists can track, phenotype, and stimulate T-cells.<ref>{{cite journal | vauthors = Peters B, Nielsen M, Sette A | title = T Cell Epitope Predictions | journal = Annual Review of Immunology | volume = 38 | issue = 1 | pages = 123–145 | date = April 2020 | pmid = 32045313 | doi = 10.1146/annurev-immunol-082119-124838 }}</ref>
+MHC class I and II epitopes can be reliably predicted by computational means alone,<ref>{{cite journal |last1=Koren |first1=E. |last2=Groot |first2=Anne De |last3=Jawa |first3=V. |last4=Beck |first4=K. |last5=Boone |first5=T. |last6=Rivera |first6=D. |last7=Li |first7=L. |last8=Mytych |first8=D. |last9=Koscec |first9=M. |last10=Weeraratne |first10=D. |last11=Swanson |first11=S. |last12=Martin |first12=W. |title=Clinical validation of the 'in silico' prediction of immunogenicity of a human recombinant therapeutic protein |journal=Institute for Immunology and Informatics Faculty Publications |date=1 January 2007 |volume=124 |issue=1 |pages=26–32 |doi=10.1016/j.clim.2007.03.544 |pmid=17490912 |s2cid=12867280 |url=https://digitalcommons.uri.edu/immunology_facpubs/69/ }}</ref> although not all in-silico T cell epitope prediction algorithms are equivalent in their accuracy.<ref>{{cite journal |last1=De Groot |first1=Anne S. |last2=Martin |first2=William |title=Reducing risk, improving outcomes: Bioengineering less immunogenic protein therapeutics |journal=Clinical Immunology |date=May 2009 |volume=131 |issue=2 |pages=189–201 |doi=10.1016/j.clim.2009.01.009 |pmid=19269256 }}</ref> There are two main methods of predicting peptide-MHC binding: data-driven and structure-based.<ref name="Sanchez-Trincado et al 2017"/> Structure based methods model the peptide-MHC structure and require great computational power.<ref name="Sanchez-Trincado et al 2017"/> Data-driven methods have higher predictive performance than structure-based methods.<ref name="Sanchez-Trincado et al 2017"/> Data-driven methods predict peptide-MHC binding based on peptide sequences that bind MHC molecules.<ref name="Sanchez-Trincado et al 2017"/> By identifying T-cell epitopes, scientists can track, phenotype, and stimulate T-cells.<ref>{{cite journal |last1=Peters |first1=Bjoern |last2=Nielsen |first2=Morten |last3=Sette |first3=Alessandro |title=T Cell Epitope Predictions |journal=Annual Review of Immunology |date=26 April 2020 |volume=38 |issue=1 |pages=123–145 |doi=10.1146/annurev-immunol-082119-124838 |pmid=32045313 |s2cid=211085860 |pmc=10878398 }}</ref><ref name="Ahmad Eweida El-Sayed 2016">{{cite journal |last1=Ahmad |first1=Tarek A. |last2=Eweida |first2=Amrou E. |last3=El-Sayed |first3=Laila H. |title=T-cell epitope mapping for the design of powerful vaccines |journal=Vaccine Reports |date=December 2016 |volume=6 |pages=13–22 |doi=10.1016/j.vacrep.2016.07.002 }}</ref><ref>{{cite journal |vauthors=Dezfulian MH, Kula T, Pranzatelli T, Kamitaki N, Meng Q, Khatri B, Perez P, Xu Q, Chang A, Kohlgruber AC, Leng Y, Jupudi AA, Joachims ML, Chiorini JA, Lessard CJ, Farris AD, Muthuswamy SK, Warner BM, Elledge SJ |title=TScan-II: A genome-scale platform for the de novo identification of CD4+ T cell epitopes |journal=Cell |volume=186 |issue=25 |pages=5569–86 |date=December 2023 |pmid=38016469 |doi=10.1016/j.cell.2023.10.024 |doi-access=free }}</ref><ref>{{cite journal |vauthors=Kula T, Dezfulian MH, Wang CI, Abdelfattah NS, Hartman ZC, Wucherpfennig KW, Lyerly HK, Elledge SJ |title=T-Scan: A Genome-wide Method for the Systematic Discovery of T Cell Epitopes |journal=Cell |volume=178 |issue=4 |pages=1016–28 |date=August 2019 |pmid=31398327 |pmc=6939866 |doi=10.1016/j.cell.2019.07.009 }}</ref>
 === B cell epitopes ===
-There are two main methods of epitope mapping: either structural or functional studies.<ref name=":2">{{cite journal | vauthors = Potocnakova L, Bhide M, Pulzova LB | title = An Introduction to B-Cell Epitope Mapping and In Silico Epitope Prediction | journal = Journal of Immunology Research | volume = 2016 | pages = 6760830 | date = 2016 | pmid = 28127568 | pmc = 5227168 | doi = 10.1155/2016/6760830 }}</ref> Methods for structurally mapping epitopes include X-ray crystallography, nuclear magnetic resonance, and electron microscopy.<ref name=":2" /> X-ray crystallography of Ag-Ab complexes is considered an accurate way to structurally map epitopes.<ref name=":2" /> Nuclear magnetic resonance can be used to map epitopes by using data about the Ag-Ab complex.<ref name=":2" /> This method does not require crystal formation but can only work on small peptides and proteins.<ref name=":2" /> Electron microscopy is a low-resolution method that can localize epitopes on larger antigens like virus particles.<ref name=":2" />
+There are two main methods of epitope mapping: either structural or functional studies.<ref name="Potocnakova et al 2016">{{cite journal |last1=Potocnakova |first1=Lenka |last2=Bhide |first2=Mangesh |last3=Pulzova |first3=Lucia Borszekova |title=An Introduction to B-Cell Epitope Mapping and In Silico Epitope Prediction |journal=Journal of Immunology Research |date=2016 |volume=2016 |pages=1–11 |doi=10.1155/2016/6760830 |pmid=28127568 |pmc=5227168 |doi-access=free }}</ref> Methods for structurally mapping epitopes include [[X-ray crystallography]], [[nuclear magnetic resonance]], and [[Electron microscope|electron microscopy]].<ref name="Potocnakova et al 2016"/> X-ray crystallography of Ag-Ab complexes is considered an accurate way to structurally map epitopes.<ref name="Potocnakova et al 2016"/> Nuclear magnetic resonance can be used to map epitopes by using data about the Ag-Ab complex.<ref name="Potocnakova et al 2016"/> This method does not require crystal formation but can only work on small peptides and proteins.<ref name="Potocnakova et al 2016"/> Electron microscopy is a low-resolution method that can localize epitopes on larger antigens like virus particles.<ref name="Potocnakova et al 2016"/>
-Methods for functionally mapping epitopes often use binding assays such as western blot, dot blot, and/or ELISA to determine antibody binding.<ref name=":2" /> Competition methods look to determine if two monoclonal antibodies (mABs) can bind to an antigen at the same time or compete with each other to bind at the same site.<ref name=":2" />  Another technique involves high-throughput [[mutagenesis]], an epitope mapping strategy developed to improve rapid mapping of conformational epitopes on structurally complex proteins.<ref>{{cite journal | vauthors = Davidson E, Doranz BJ | title = A high-throughput shotgun mutagenesis approach to mapping B-cell antibody epitopes | journal = Immunology | volume = 143 | issue = 1 | pages = 13–20 | date = September 2014 | pmid = 24854488 | pmc = 4137951 | doi = 10.1111/imm.12323 }}</ref> Mutagenesis uses randomly/site-directed mutations at individual residues to map epitopes.<ref name=":2" /> B-cell epitope mapping can be used for the development of antibody therapeutics, peptide-based vaccines, and immunodiagnostic tools.<ref name=":2" />
+Methods for functionally mapping epitopes often use binding assays such as [[western blot]], [[dot blot]], and/or [[ELISA]] to determine antibody binding.<ref name="Potocnakova et al 2016"/> Competition methods look to determine if two [[Monoclonal antibody|monoclonal antibodies]] (mABs) can bind to an antigen at the same time or compete with each other to bind at the same site.<ref name="Potocnakova et al 2016"/> Another technique involves high-throughput [[mutagenesis]], an epitope mapping strategy developed to improve rapid mapping of conformational epitopes on structurally complex proteins.<ref>{{cite journal |last1=Davidson |first1=Edgar |last2=Doranz |first2=Benjamin J. |title=A high-throughput shotgun mutagenesis approach to mapping B-cell antibody epitopes |journal=Immunology |date=September 2014 |volume=143 |issue=1 |pages=13–20 |doi=10.1111/imm.12323 |pmid=24854488 |pmc=4137951 }}</ref> Mutagenesis uses randomly/site-directed mutations at individual residues to map epitopes.<ref name="Potocnakova et al 2016"/> B-cell epitope mapping can be used for the development of antibody therapeutics, peptide-based vaccines, and immunodiagnostic tools.<ref name="Potocnakova et al 2016"/><ref name="Ahmad Eweida Sheweita 2016">{{cite journal |last1=Ahmad |first1=Tarek A. |last2=Eweida |first2=Amrou E. |last3=Sheweita |first3=Salah A. |title=B-cell epitope mapping for the design of vaccines and effective diagnostics |journal=Trials in Vaccinology |date=2016 |volume=5 |pages=71–83 |doi=10.1016/j.trivac.2016.04.003 |doi-access=free }}</ref>
 ==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 [[Protein biosynthesis|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]], [[Polyhistidine-tag|6xHis]],<ref>{{cite book |title= Molecular bio-methods handbook| vauthors = Walker J, Rapley R |year= 2008|publisher= Humana Press |isbn= 978-1-60327-374-9|page=467}}</ref> V5-tag and OLLAS.<ref>{{cite web|last=Novus|first=Biologicals|title=OLLAS Epitope Tag|url=http://www.novusbio.com/ollas|publisher=Novus Biologicals|access-date=23 November 2011}}</ref> Peptides can also be bound by proteins that form covalent bonds to the peptide, allowing irreversible immobilisation<ref>{{cite journal | vauthors = Zakeri B, Fierer JO, Celik E, Chittock EC, Schwarz-Linek U, Moy VT, Howarth M | title = Peptide tag forming a rapid covalent bond to a protein, through engineering a bacterial adhesin | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 12 | pages = E690-7 | date = March 2012 | pmid = 22366317 | pmc = 3311370 | doi = 10.1073/pnas.1115485109 | bibcode = 2012PNAS..109E.690Z }}</ref> These strategies have also been successfully applied to the development of "epitope-focused" vaccine design.<ref>{{cite journal | vauthors = Correia BE, Bates JT, Loomis RJ, Baneyx G, Carrico C, Jardine JG, Rupert P, Correnti C, Kalyuzhniy O, Vittal V, Connell MJ, Stevens E, Schroeter A, Chen M, Macpherson S, Serra AM, Adachi Y, Holmes MA, Li Y, Klevit RE, Graham BS, Wyatt RT, Baker D, Strong RK, Crowe JE, Johnson PR, Schief WR | display-authors = 6 | title = Proof of principle for epitope-focused vaccine design | journal = Nature | volume = 507 | issue = 7491 | pages = 201–6 | date = March 2014 | pmid = 24499818 | pmc = 4260937 | doi = 10.1038/nature12966 | bibcode = 2014Natur.507..201C }}</ref><ref>{{cite journal | vauthors = McBurney SP, Sunshine JE, Gabriel S, Huynh JP, Sutton WF, Fuller DH, Haigwood NL, Messer WB | display-authors = 6 | title = Evaluation of protection induced by a dengue virus serotype 2 envelope domain III protein scaffold/DNA vaccine in non-human primates | journal = Vaccine | volume = 34 | issue = 30 | pages = 3500–7 | date = June 2016 | pmid = 27085173 | pmc = 4959041 | doi = 10.1016/j.vaccine.2016.03.108 | author-link7 = Nancy Haigwood }}</ref>
+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 [[Protein biosynthesis|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]], [[Polyhistidine-tag|6xHis]],<ref>{{cite book |title= Molecular bio-methods handbook| veditors = Walker J, Rapley R |year= 2008|publisher= Humana Press |isbn= 978-1-60327-374-9 |doi=10.1007/978-1-60327-375-6 |edition=2nd |chapter=Protein–Protein Interactions |chapter-url=https://link.springer.com/protocol/10.1007/978-1-60327-375-6_30 |pages=463–494, See p. 467 |vauthors= Park HR, Cockrell LM, Du Y, Kasinski A, Havel J, Zhao J, Reyes-Turcu F, Wilkinson KD, Fu H }}</ref> V5-tag and OLLAS.<ref>{{cite web|last=Novus|first=Biologicals|title=OLLAS Epitope Tag|url=http://www.novusbio.com/ollas|publisher=Novus Biologicals|access-date=23 November 2011}}</ref> Peptides can also be bound by proteins that form covalent bonds to the peptide, allowing irreversible immobilisation.<ref>{{cite journal | vauthors = Zakeri B, Fierer JO, Celik E, Chittock EC, Schwarz-Linek U, Moy VT, Howarth M | title = Peptide tag forming a rapid covalent bond to a protein, through engineering a bacterial adhesin | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 12 | pages = E690–7 | date = March 2012 | pmid = 22366317 | pmc = 3311370 | doi = 10.1073/pnas.1115485109 | bibcode = 2012PNAS..109E.690Z | doi-access = free }}</ref> These strategies have also been successfully applied to the development of "epitope-focused" vaccine design.<ref>{{cite journal | vauthors = Correia BE, Bates JT, Loomis RJ, Baneyx G, Carrico C, Jardine JG, Rupert P, Correnti C, Kalyuzhniy O, Vittal V, Connell MJ, Stevens E, Schroeter A, Chen M, Macpherson S, Serra AM, Adachi Y, Holmes MA, Li Y, Klevit RE, Graham BS, Wyatt RT, Baker D, Strong RK, Crowe JE, Johnson PR, Schief WR | display-authors = 6 | title = Proof of principle for epitope-focused vaccine design | journal = Nature | volume = 507 | issue = 7491 | pages = 201–6 | date = March 2014 | pmid = 24499818 | pmc = 4260937 | doi = 10.1038/nature12966 | bibcode = 2014Natur.507..201C }}</ref><ref>{{cite journal | vauthors = McBurney SP, Sunshine JE, Gabriel S, Huynh JP, Sutton WF, Fuller DH, Haigwood NL, Messer WB | display-authors = 6 | title = Evaluation of protection induced by a dengue virus serotype 2 envelope domain III protein scaffold/DNA vaccine in non-human primates | journal = Vaccine | volume = 34 | issue = 30 | pages = 3500–7 | date = June 2016 | pmid = 27085173 | pmc = 4959041 | doi = 10.1016/j.vaccine.2016.03.108 | author-link7 = Nancy Haigwood }}</ref>
 == Epitope-based vaccines ==
 {{Main articles|Peptide vaccine}}
-The first epitope-based vaccine was developed in 1985 by Jacob et al.<ref name=":3">{{cite journal | vauthors = Parvizpour S, Pourseif MM, Razmara J, Rafi MA, Omidi Y | title = Epitope-based vaccine design: a comprehensive overview of bioinformatics approaches | journal = Drug Discovery Today | volume = 25 | issue = 6 | pages = 1034–1042 | date = June 2020 | pmid = 32205198 | doi = 10.1016/j.drudis.2020.03.006 }}</ref> Epitope-based vaccines stimulate humoral and cellular immune responses using isolated B-cell or T-cell epitopes.<ref name=":3" /> These vaccines can use multiple epitopes to increase their efficacy.<ref name=":3" /> To find epitopes to use for the vaccine, in silico mapping is often used.<ref name=":3" /> Once candidate epitopes are found, the constructs are engineered and tested for vaccine efficiency.<ref name=":3" /> While epitope-based vaccines are generally safe, one possible side effect are cytokine storms.<ref name=":3" />
+The first epitope-based vaccine was developed in 1985 by Jacob et al.<ref name="Parvizpour et al 2020">{{cite journal |last1=Parvizpour |first1=Sepideh |last2=Pourseif |first2=Mohammad M. |last3=Razmara |first3=Jafar |last4=Rafi |first4=Mohammad A. |last5=Omidi |first5=Yadollah |title=Epitope-based vaccine design: a comprehensive overview of bioinformatics approaches |journal=Drug Discovery Today |date=June 2020 |volume=25 |issue=6 |pages=1034–42 |doi=10.1016/j.drudis.2020.03.006 |pmid=32205198 |s2cid=214629963 }}</ref> Epitope-based vaccines stimulate [[Humoral immunity|humoral]] and [[Cell-mediated immunity|cellular immune]] responses using isolated B-cell or T-cell epitopes.<ref name="Parvizpour et al 2020"/><ref name="Ahmad Eweida Sheweita 2016"/><ref name="Ahmad Eweida El-Sayed 2016"/> These vaccines can use multiple epitopes to increase their efficacy.<ref name="Parvizpour et al 2020"/> To find epitopes to use for the vaccine, [[in silico]] mapping is often used.<ref name="Parvizpour et al 2020"/> Once candidate epitopes are found, the constructs are engineered and tested for vaccine efficiency.<ref name="Parvizpour et al 2020"/> While epitope-based vaccines are generally safe, one possible side effect is cytokine storms.<ref name="Parvizpour et al 2020"/>
 ==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.<ref>{{cite book | vauthors = Hans-Werner V |date=2005 |chapter=Neoantigen-Forming Chemicals | title = Encyclopedic Reference of Immunotoxicology |volume= |issue= |page=475 |doi=10.1007/3-540-27806-0_1063|isbn=978-3-540-44172-4 }}</ref> Neoantigens are often associated with [[tumor antigen]]s and are found in oncogenic cells.<ref>Neoantigen. (n.d.) Mosby's Medical Dictionary, 8th edition. (2009). Retrieved February 9, 2015 from [http://medical-dictionary.thefreedictionary.com/neoantigen Medical Dictionary Online]</ref> 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]].
+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.<ref>{{cite book | vauthors = Hans-Werner V |date=2005 |chapter=Neoantigen-Forming Chemicals | title = Encyclopedic Reference of Immunotoxicology |page=475 |doi=10.1007/3-540-27806-0_1063|isbn=978-3540441724 }}</ref> Neoantigens are often associated with [[tumor antigen]]s and are found in oncogenic cells.<ref>Neoantigen. (n.d.) Mosby's Medical Dictionary, 8th edition. (2009). Retrieved February 9, 2015 from [http://medical-dictionary.thefreedictionary.com/neoantigen Medical Dictionary Online]</ref> 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]].{{cn|date=November 2023}}
 == See also ==
+* [[Cryptotope]]
 * [[Epitope binning]]
 * [[Mimotope]]
@@ Line 43: / Line 45: @@
 * [[Protein tag]]
 * [[TimeSTAMP protein labelling]]
-* [[Cryptotope]]
 == References ==
-{{reflist}}
+{{Reflist}}
 == External links ==
@@ Line 54: / Line 55: @@
 ===Epitope prediction methods===
 {{refbegin}}
-* {{cite journal | vauthors = Rubinstein ND, Mayrose I, Martz E, Pupko T | title = Epitopia: a web-server for predicting B-cell epitopes | journal = BMC Bioinformatics | volume = 10 | pages = 287 | date = September 2009 | pmid = 19751513 | pmc = 2751785 | doi = 10.1186/1471-2105-10-287 }}
+* {{cite journal | vauthors = Rubinstein ND, Mayrose I, Martz E, Pupko T | title = Epitopia: a web-server for predicting B-cell epitopes | journal = BMC Bioinformatics | volume = 10 | pages = 287 | date = September 2009 | pmid = 19751513 | pmc = 2751785 | doi = 10.1186/1471-2105-10-287 | doi-access = free }}
 * {{cite journal | vauthors = Rubinstein ND, Mayrose I, Pupko T | title = A machine-learning approach for predicting B-cell epitopes | journal = Molecular Immunology | volume = 46 | issue = 5 | pages = 840–7 | date = February 2009 | pmid = 18947876 | doi = 10.1016/j.molimm.2008.09.009 }}
-* {{cite journal | vauthors = Saravanan V, Gautham N | title = Harnessing Computational Biology for Exact Linear B-Cell Epitope Prediction: A Novel Amino Acid Composition-Based Feature Descriptor | journal = Omics | volume = 19 | issue = 10 | pages = 648–58 | date = October 2015 | pmid = 26406767 | doi = 10.1089/omi.2015.0095 }}
+* {{cite journal | vauthors = Saravanan V, Gautham N | title = Harnessing Computational Biology for Exact Linear B-Cell Epitope Prediction: A Novel Amino Acid Composition-Based Feature Descriptor | journal = Omics | volume = 19 | issue = 10 | pages = 648–658 | date = October 2015 | pmid = 26406767 | doi = 10.1089/omi.2015.0095 }}
-* {{cite journal | vauthors = Singh H, Ansari HR, Raghava GP | title = Improved method for linear B-cell epitope prediction using antigen's primary sequence | journal = Plos One | volume = 8 | issue = 5 | pages = e62216 | date = 2013 | pmid = 23667458 | pmc = 3646881 | doi = 10.1371/journal.pone.0062216 }}
+* {{cite journal | vauthors = Singh H, Ansari HR, Raghava GP | title = Improved method for linear B-cell epitope prediction using antigen's primary sequence | journal = PLOS ONE | volume = 8 | issue = 5 | pages = e62216 | date = 2013 | pmid = 23667458 | pmc = 3646881 | doi = 10.1371/journal.pone.0062216 | bibcode = 2013PLoSO...862216S | doi-access = free }}
 {{refend}}
 ===Epitope databases===
-*[http://www.imtech.res.in/raghava/mhcbn/ MHCBN: A database of MHC/TAP binder and T-cell epitopes]
+* [http://www.imtech.res.in/raghava/mhcbn/ MHCBN: A database of MHC/TAP binder and T-cell epitopes]
-*[http://www.imtech.res.in/raghava/bcipep/ Bcipep: A database of B-cell epitopes]
+* [http://www.imtech.res.in/raghava/bcipep/ Bcipep: A database of B-cell epitopes]
-* [http://www.syfpeithi.de SYFPEITHI – First online database of T cell epitopes]
+* [http://www.syfpeithi.de SYFPEITHI — First online database of T cell epitopes]
-* [http://www.immuneepitope.org IEDB –  Database of T and B cell epitopes with annotation of recognition context – NIH funded]
+* [http://www.immuneepitope.org IEDB —  Database of T and B cell epitopes with annotation of recognition context — NIH funded]
-* [https://web.archive.org/web/20060902162039/http://www.jenner.ac.uk/antijen/ ANTIJEN – T and B cell epitope database at the Jenner institute, UK]
+* [https://web.archive.org/web/20060902162039/http://www.jenner.ac.uk/antijen/ ANTIJEN — T and B cell epitope database at the Jenner institute, UK]
-* [https://web.archive.org/web/20061006031248/http://imgt.cines.fr/ IMGT/3Dstructure-DB – Three-dimensional structures of B and T cell epitopes with annotation of IG and TR – IMGT, Montpellier, France]
+* [https://web.archive.org/web/20061006031248/http://imgt.cines.fr/ IMGT/3Dstructure-DB — Three-dimensional structures of B and T cell epitopes with annotation of IG and TR — IMGT, Montpellier, France]
-* [http://sedb.bicpu.edu.in/ SEDB: A Structural Epitope Database – Pondicheery University, DIT funded]
+* [http://sedb.bicpu.edu.in/ SEDB: A Structural Epitope Database — Pondicheery University, DIT funded]
 * {{MeshName|Epitopes}}
 {{Immune system}}
+{{Authority control}}
 [[Category:Antigenic determinant|*]]