Knowledge

Epitope

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193:. X-ray crystallography of Ag-Ab complexes is considered an accurate way to structurally map epitopes. Nuclear magnetic resonance can be used to map epitopes by using data about the Ag-Ab complex. This method does not require crystal formation but can only work on small peptides and proteins. Electron microscopy is a low-resolution method that can localize epitopes on larger antigens like virus particles. 216:, an epitope mapping strategy developed to improve rapid mapping of conformational epitopes on structurally complex proteins. Mutagenesis uses randomly/site-directed mutations at individual residues to map epitopes. B-cell epitope mapping can be used for the development of antibody therapeutics, peptide-based vaccines, and immunodiagnostic tools. 173:
model the peptide-MHC structure and require great computational power. Data-driven methods have higher predictive performance than structure-based methods. Data-driven methods predict peptide-MHC binding based on peptide sequences that bind MHC molecules. By identifying T-cell epitopes, scientists can track, phenotype, and stimulate T-cells.
153:). 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. 172:
MHC class I and II epitopes can be reliably predicted by computational means alone, although not all in-silico T cell epitope prediction algorithms are equivalent in their accuracy. There are two main methods of predicting peptide-MHC binding: data-driven and structure-based. Structure based methods
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The part of the antigen that immunoglobulin or antibodies bind to is called a B-cell epitope. B cell epitopes can be divided into two groups: conformational or linear. B cell epitopes are mainly conformational. There are additional epitope types when the quaternary structure is considered. Epitopes
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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
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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".
70:, based on their structure and interaction with the paratope. 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 256:, V5-tag and OLLAS. Peptides can also be bound by proteins that form covalent bonds to the peptide, allowing irreversible immobilisation. These strategies have also been successfully applied to the development of "epitope-focused" vaccine design. 123:
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, and non-classical MHC molecules also present non-peptidic epitopes such as
236:, 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 1131:
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).
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mapping is often used. Once candidate epitopes are found, the constructs are engineered and tested for vaccine efficiency. While epitope-based vaccines are generally safe, one possible side effect is cytokine storms.
141:. Neotopes are epitopes that are only recognized while in a specific quaternary structure and the residues of the epitope can span multiple protein subunits. Neotopes are not recognized once the subunits dissociate. 1613:
Parvizpour, Sepideh; Pourseif, Mohammad M.; Razmara, Jafar; Rafi, Mohammad A.; Omidi, Yadollah (June 2020). "Epitope-based vaccine design: a comprehensive overview of bioinformatics approaches".
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and are found in oncogenic cells. Neoantigens and, by extension, neoantigenic determinants can be formed when a protein undergoes further modification within a biochemical pathway such as
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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".
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Saravanan V, Gautham N (October 2015). "Harnessing Computational Biology for Exact Linear B-Cell Epitope Prediction: A Novel Amino Acid Composition-Based Feature Descriptor".
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Briggs S, Price MR, Tendler SJ (1993). "Fine specificity of antibody recognition of carcinoma-associated epithelial mucins: antibody binding to synthetic peptide epitopes".
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Epitopes are sometimes cross-reactive. This property is exploited by the immune system in regulation by anti-idiotypic antibodies (originally proposed by Nobel laureate
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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".
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responses using isolated B-cell or T-cell epitopes. These vaccines can use multiple epitopes to increase their efficacy. To find epitopes to use for the vaccine,
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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
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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).
1953: 212:(mABs) can bind to an antigen at the same time or compete with each other to bind at the same site. Another technique involves high-throughput 319:. This, by altering the structure of the protein, can produce new epitopes that are called neoantigenic determinants as they give rise to new 1009:
De Groot, Anne S.; Martin, William (May 2009). "Reducing risk, improving outcomes: Bioengineering less immunogenic protein therapeutics".
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There are two main methods of epitope mapping: either structural or functional studies. Methods for structurally mapping epitopes include
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Antigens can bind in pockets or grooves, or on extended surfaces in the binding sites of antibodies (Janeway Immunobiology Figure 3.8)
1555:"Evaluation of protection induced by a dengue virus serotype 2 envelope domain III protein scaffold/DNA vaccine in non-human primates" 1104:
Ahmad, Tarek A.; Eweida, Amrou E.; El-Sayed, Laila H. (December 2016). "T-cell epitope mapping for the design of powerful vaccines".
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IMGT/3Dstructure-DB β€” Three-dimensional structures of B and T cell epitopes with annotation of IG and TR β€” IMGT, Montpellier, France
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techniques genetic sequences coding for epitopes that are recognized by common antibodies can be fused to the gene. Following
1398: 938: 783: 1704: 1939: 1673: 55:, sequences derived from the host that can be recognized (as in the case of autoimmune diseases) are also epitopes. 2285: 108: 104: 1173:
Kula T, Dezfulian MH, Wang CI, Abdelfattah NS, Hartman ZC, Wucherpfennig KW, Lyerly HK, Elledge SJ (August 2019).
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Rubinstein ND, Mayrose I, Pupko T (February 2009). "A machine-learning approach for predicting B-cell epitopes".
964:"Clinical validation of the 'in silico' prediction of immunogenicity of a human recombinant therapeutic protein" 2382: 2280: 1906: 2223: 366: 1705:
Antibodies bind to conformational shapes on the surfaces of antigens (Janeway Immunobiology Section 3.8)
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The first epitope-based vaccine was developed in 1985 by Jacob et al. Epitope-based vaccines stimulate
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Neoantigen. (n.d.) Mosby's Medical Dictionary, 8th edition. (2009). Retrieved February 9, 2015 from
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that has not been previously recognized by the immune system. Neoantigens are often associated with
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Park HR, Cockrell LM, Du Y, Kasinski A, Havel J, Zhao J, Reyes-Turcu F, Wilkinson KD, Fu H (2008).
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Ferdous, Saba; Kelm, Sebastian; Baker, Terry S.; Shi, Jiye; Martin, Andrew C. R. (1 October 2019).
1378: 2289: 2047: 1439:"Peptide tag forming a rapid covalent bond to a protein, through engineering a bacterial adhesin" 100: 1709: 2311: 2029: 1965: 320: 275: 63: 1553:
McBurney SP, Sunshine JE, Gabriel S, Huynh JP, Sutton WF, Fuller DH, et al. (June 2016).
526:"Differential effects of flanking residues on presentation of epitopes from chimeric peptides" 2258: 2114: 2092: 1902:
IEDB β€” Database of T and B cell epitopes with annotation of recognition context β€” NIH funded
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Correia BE, Bates JT, Loomis RJ, Baneyx G, Carrico C, Jardine JG, et al. (March 2014).
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Zakeri B, Fierer JO, Celik E, Chittock EC, Schwarz-Linek U, Moy VT, Howarth M (March 2012).
2275: 2208: 2119: 2043: 1839: 1509: 1450: 490: 233: 1134:"TScan-II: A genome-scale platform for the de novo identification of CD4+ T cell epitopes" 1061: 8: 2335: 2270: 2253: 2087: 2005: 209: 190: 1843: 1513: 1454: 1070: 1045: 963: 494: 2155: 1862: 1828:"Improved method for linear B-cell epitope prediction using antigen's primary sequence" 1827: 1751: 1724: 1638: 1579: 1554: 1530: 1497: 1473: 1438: 1318: 1293: 1269: 1242: 1199: 1174: 1083: 991: 889: 862: 838: 811: 721: 604: 458: 431: 412: 83:
residues to adopt the epitope's 3-D conformation. 90% of epitopes are conformational.
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Anfinsen CB (July 1973). "Principles that govern the folding of protein chains".
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Proceedings of the National Academy of Sciences of the United States of America
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to determine antibody binding. Competition methods look to determine if two
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Methods for functionally mapping epitopes often use binding assays such as
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Sanchez-Trincado, Jose L.; Gomez-Perosanz, Marta; Reche, Pedro A. (2017).
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SEDB: A Structural Epitope Database β€” Pondicheery University, DIT funded
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Potocnakova, Lenka; Bhide, Mangesh; Pulzova, Lucia Borszekova (2016).
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Bergmann CC, Tong L, Cua R, Sensintaffar J, Stohlman S (August 1994).
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Peters, Bjoern; Nielsen, Morten; Sette, Alessandro (26 April 2020).
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ANTIJEN β€” T and B cell epitope database at the Jenner institute, UK
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Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002).
346: 245: 201: 48: 36: 2356: 2170: 1990: 351: 300: 249: 237: 59: 28: 1415: 1130: 47:. The part of an antibody that binds to the epitope is called a 2328: 2316: 2061: 2012: 1901: 812:"Fundamentals and Methods for T- and B-Cell Epitope Prediction" 241: 96: 44: 40: 1344:
Ahmad, Tarek A.; Eweida, Amrou E.; Sheweita, Salah A. (2016).
925:. Methods in Molecular Biology. Vol. 524. pp. 3–20. 805: 803: 801: 799: 797: 795: 1723:
Rubinstein ND, Mayrose I, Martz E, Pupko T (September 2009).
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Institute for Immunology and Informatics Faculty Publications
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Regenmortel, Marc H.V. (2009). "What is a B-Cell Epitope?".
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that are masked when protein subunits aggregate are called
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present MHC class I peptides. T cell epitopes presented by
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MHCBN: A database of MHC/TAP binder and T-cell epitopes
1725:"Epitopia: a web-server for predicting B-cell epitopes" 1498:"Proof of principle for epitope-focused vaccine design" 1292:
Davidson, Edgar; Doranz, Benjamin J. (September 2014).
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Bergmann CC, Yao Q, Ho CK, Buckwold SL (October 1996).
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Hans-Werner V (2005). "Neoantigen-Forming Chemicals".
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SYFPEITHI β€” First online database of T cell epitopes
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Recognition requires separate, specific 62:antigens are divided into two categories, 1924:at the U.S. National Library of Medicine 1861: 1851: 1750: 1740: 1578: 1529: 1472: 1462: 1361: 1317: 1268: 1258: 1198: 1149: 1069: 888: 878: 837: 827: 590: 549: 457: 447: 259: 480: 432:"CED: a conformational epitope database" 75:epitope is not determined solely by the 1826:Singh H, Ansari HR, Raghava GP (2013). 2375: 1935: 1892:Bcipep: A database of B-cell epitopes 1062:10.1146/annurev-immunol-082119-124838 109:professional antigen-presenting cells 1880: 176: 167: 13: 156: 131: 91: 14: 2394: 1698: 1413: 144: 115:peptides, whereas most nucleated 1381:. In Walker J, Rapley R (eds.). 401:10.1016/j.biotechadv.2020.107653 105:major histocompatibility complex 51:. Although epitopes are usually 1682: 1649: 1546: 1489: 1430: 1407: 1370: 1285: 1166: 1124: 1037: 1002: 955: 854: 767: 542:10.1128/JVI.68.8.5306-5310.1994 430:Huang J, Honda W (April 2006). 219: 2281:Immunoglobulin class switching 1383:Molecular bio-methods handbook 1379:"Protein–Protein Interactions" 1247:Journal of Immunology Research 816:Journal of Immunology Research 732: 685: 650: 615: 566: 517: 474: 423: 379: 1: 1571:10.1016/j.vaccine.2016.03.108 776:Molecular biology of the cell 753:10.1016/j.vaccine.2014.04.039 372: 1853:10.1371/journal.pone.0062216 1782:10.1016/j.molimm.2008.09.009 1627:10.1016/j.drudis.2020.03.006 1363:10.1016/j.trivac.2016.04.003 1118:10.1016/j.vacrep.2016.07.002 1046:"T Cell Epitope Predictions" 710:10.1016/j.molimm.2019.09.014 659:Journal of Molecular Biology 636:10.1016/0959-8049(93)90181-E 503:10.1126/science.181.4096.223 107:(MHC) molecules. In humans, 7: 1050:Annual Review of Immunology 931:10.1007/978-1-59745-450-6_1 592:10.4049/jimmunol.157.8.3242 367:TimeSTAMP protein labelling 330: 224:Epitopes are often used in 111:are specialized to present 86: 10: 2399: 2110:Polyclonal B cell response 1716:Epitope prediction methods 1666:10.1007/3-540-27806-0_1063 1191:10.1016/j.cell.2019.07.009 1151:10.1016/j.cell.2023.10.024 1023:10.1016/j.clim.2009.01.009 980:10.1016/j.clim.2007.03.544 624:European Journal of Cancer 357:Polyclonal B cell response 299:, which is a newly formed 263: 187:nuclear magnetic resonance 160: 103:, where they are bound to 31:that is recognized by the 2344: 2302: 2244: 2145: 2075: 1983: 1976: 1690:Medical Dictionary Online 1391:10.1007/978-1-60327-375-6 923:Epitope Mapping Protocols 880:10.1186/1745-7580-6-S2-S2 1926:Medical Subject Headings 1742:10.1186/1471-2105-10-287 293:neoantigenic determinant 287:Neoantigenic determinant 1464:10.1073/pnas.1115485109 101:antigen-presenting cell 64:conformational epitopes 2224:Tolerance in pregnancy 1966:adaptive immune system 671:10.1006/jmbi.1998.1907 389:Biotechnology Advances 321:antigenic determinants 260:Epitope-based vaccines 2383:Antigenic determinant 2259:Somatic hypermutation 2093:Polyclonal antibodies 2088:Monoclonal antibodies 1811:10.1089/omi.2015.0095 1350:Trials in Vaccinology 579:Journal of Immunology 449:10.1186/1471-2172-7-7 210:monoclonal antibodies 183:X-ray crystallography 25:antigenic determinant 2276:Junctional diversity 2044:Antigen presentation 1770:Molecular Immunology 1615:Drug Discovery Today 1414:Novus, Biologicals. 1260:10.1155/2016/6760830 829:10.1155/2017/2680160 698:Molecular Immunology 27:, is the part of an 2271:V(D)J recombination 2254:Affinity maturation 2006:Antigenic variation 1844:2013PLoSO...862216S 1522:10.1038/nature12966 1514:2014Natur.507..201C 1455:2012PNAS..109E.690Z 1418:. Novus Biologicals 1416:"OLLAS Epitope Tag" 1011:Clinical Immunology 530:Journal of Virology 495:1973Sci...181..223A 295:is an epitope on a 191:electron microscopy 1729:BMC Bioinformatics 72:tertiary structure 35:, specifically by 2370: 2369: 2298: 2297: 2048:professional APCs 1881:Epitope databases 1400:978-1-60327-374-9 1310:10.1111/imm.12323 940:978-1-934115-17-6 867:Immunome Research 785:978-0-8153-3218-3 489:(4096): 223–230. 81:primary structure 77:primary structure 53:non-self proteins 2390: 2264:Clonal selection 2236:Immune privilege 2231:Immunodeficiency 2186:Cross-reactivity 2176:Hypersensitivity 1981: 1980: 1956: 1949: 1942: 1933: 1932: 1875: 1865: 1855: 1822: 1793: 1764: 1754: 1744: 1692: 1686: 1680: 1679: 1653: 1647: 1646: 1610: 1593: 1592: 1582: 1550: 1544: 1543: 1533: 1493: 1487: 1486: 1476: 1466: 1434: 1428: 1427: 1425: 1423: 1411: 1405: 1404: 1374: 1368: 1367: 1365: 1341: 1332: 1331: 1321: 1289: 1283: 1282: 1272: 1262: 1238: 1213: 1212: 1202: 1170: 1164: 1163: 1153: 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302: 298: 294: 284: 281: 277: 273: 267: 257: 255: 251: 247: 243: 239: 235: 231: 227: 217: 215: 211: 207: 203: 199: 194: 192: 188: 184: 174: 164: 154: 152: 142: 140: 129: 127: 122: 118: 117:somatic cells 114: 110: 106: 102: 98: 84: 82: 78: 73: 69: 65: 61: 56: 54: 50: 46: 42: 38: 34: 33:immune system 30: 26: 22: 2181:Inflammation 2166:Alloimmunity 2161:Autoimmunity 2146:Immunity vs. 2098:Autoantibody 2019: 1996:Superantigen 1835: 1831: 1802: 1798: 1776:(5): 840–7. 1773: 1769: 1732: 1728: 1684: 1657: 1651: 1618: 1614: 1562: 1558: 1548: 1505: 1501: 1491: 1446: 1442: 1432: 1420:. Retrieved 1409: 1382: 1372: 1353: 1349: 1304:(1): 13–20. 1301: 1297: 1287: 1250: 1246: 1182: 1178: 1168: 1141: 1137: 1126: 1109: 1105: 1053: 1049: 1039: 1014: 1010: 1004: 974:(1): 26–32. 971: 967: 957: 922: 870: 866: 856: 819: 815: 775: 769: 744: 740: 734: 701: 697: 687: 662: 658: 652: 630:(2): 230–7. 627: 623: 617: 582: 578: 568: 533: 529: 519: 486: 482: 476: 439: 435: 425: 392: 388: 381: 292: 290: 269: 223: 220:Epitope tags 198:western blot 195: 180: 171: 148: 135: 113:MHC class II 95: 57: 24: 20: 18: 2304:Lymphocytes 1963:Lymphocytic 1422:23 November 704:: 643–650. 362:Protein tag 317:proteolysis 214:mutagenesis 139:cryptotopes 126:glycolipids 121:MHC class I 2345:Substances 2209:Peripheral 2197:Inaction: 2076:Antibodies 2057:Macrophage 1970:complement 1298:Immunology 395:: 107653. 373:References 337:Cryptotope 325:antibodies 297:neoantigen 226:proteomics 37:antibodies 2362:Cytolysin 2352:Cytokines 2199:Tolerance 2148:tolerance 2067:Immunogen 1643:214629963 1356:: 71–83. 1112:: 13–22. 1088:211085860 726:202747810 417:226276355 280:in silico 234:synthesis 204:, and/or 2377:Category 2312:Cellular 2156:Immunity 2154:Action: 2137:Paratope 2125:Idiotype 2115:Allotype 2083:Antibody 2037:Mimotope 2001:Allergen 1984:Antigens 1977:Lymphoid 1922:Epitopes 1872:23667458 1832:PLOS ONE 1819:26406767 1790:18947876 1761:19751513 1635:32205198 1589:27085173 1540:24499818 1483:22366317 1328:24854488 1279:28127568 1253:: 1–11. 1209:31398327 1160:38016469 1080:32045313 1071:10878398 1031:19269256 996:12867280 988:17490912 949:19377933 899:21067544 848:29445754 822:: 1–14. 761:24795226 718:31546099 609:24717835 468:16603068 409:33157154 347:Mimotope 331:See also 246:FLAG-tag 202:dot blot 87:Function 49:paratope 2357:Opsonin 2336:NK cell 2324:Humoral 2204:Central 2171:Allergy 2120:Isotype 2020:Epitope 1991:Antigen 1863:3646881 1840:Bibcode 1752:2751785 1735:: 287. 1580:4959041 1559:Vaccine 1531:4260937 1510:Bibcode 1474:3311370 1451:Bibcode 1319:4137951 1270:5227168 1200:6939866 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513:. 501:: 493:: 470:. 446:: 440:7 419:. 399::

Index

antigen
immune system
antibodies
B cells
T cells
paratope
non-self proteins
protein
conformational epitopes
linear epitopes
tertiary structure
primary structure
primary structure
T cell
antigen-presenting cell
major histocompatibility complex
professional antigen-presenting cells
MHC class II
somatic cells
MHC class I
glycolipids
cryptotopes
Niels Kaj Jerne
Epitope mapping
X-ray crystallography
nuclear magnetic resonance
electron microscopy
western blot
dot blot
ELISA

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