352:, this technique uses a library of oligopeptide sequences from overlapping and non-overlapping segments of a target protein, and tests for their ability to bind the antibody of interest. This method is fast, relatively inexpensive, and specifically suited to profile epitopes for large numbers of candidate antibodies against a defined target. The epitope mapping resolution depends on the number of overlapping peptides that are used. The main disadvantage of this approach is that discontinuous epitopes are deconstructed into smaller peptides, which can cause lower binding affinities. However, advances have been made with technologies such as constrained peptides, which can be used to mimic conformational as well as discontinuous epitopes. For example, an antibody against
408:
native solution, and does not introduce any modifications (e.g. mutation) to either the antigen or the antibody. HDX epitope mapping has also been demonstrated to be the effective method to rapidly supply complete information for epitope structure. It does not usually provide data at the level of amino acid, but this limitation is being improved by new technology advancements. It has recently been recommended as a fast and cost-effective epitope mapping approach, using the complex protein system influenza hemagglutinin as an example.
191:
398:
visualize the epitope. Benefits of high-throughput shotgun mutagenesis epitope mapping include: 1) the ability to identify both linear and conformational epitopes, 2) a shorter assay time than other methods, 3) the presentation of properly folded and post-translationally modified proteins, and 4) the ability to identify key amino acids that drive the energetic interactions (energetic "hot spots" of the epitope).
335:
approaches are technically challenging, time-consuming, and expensive, and not all proteins are amenable to crystallization. Moreover, these techniques are not always feasible due to the difficulty in obtaining sufficient quantities of correctly folded and processed protein. Finally, neither technique can distinguish key epitope residues (energetic "hot spots") for mAbs that bind to the same group of amino acids.
462:
261:
20:
397:
clones from the library are individually arrayed in 384-well microplates, expressed in human cells, and tested for antibody binding. Amino acids of the target required for antibody binding are identified by a loss of immunoreactivity. These residues are mapped onto structures of the target protein to
356:
was mapped in a study using array-based oligopeptide scanning, by combining non-adjacent peptide sequences from different parts of the target protein and enforcing conformational rigidity onto this combined peptide (e.g., by using CLIPS scaffolds). Replacement analysis on peptides also allows single
407:
This method gives information about the solvent accessibility of various parts of the antigen and antibody, demonstrating reduced solvent accessibility in regions of protein-protein interactions. One of its advantages is that it determines the interaction site of the antigen-antibody complex in its
374:
of amino acids are introduced into the sequence of the target protein. Binding of an antibody to each mutated protein is tested to identify the amino acids that comprise the epitope. This technique can be used to map both linear and conformational epitopes but is labor-intensive and time-consuming,
334:
X-ray co-crystallography has historically been regarded as the gold-standard approach for epitope mapping because it allows direct visualization of the interaction between the antigen and antibody. Cryo-EM can similarly provide high-resolution maps of antibody-antigen interactions. However, both
181:
these complex proteins. Membrane proteins frequently have short antigenic regions (epitopes) that fold correctly only when in the context of a lipid bilayer. As a result, mAb epitopes on these membrane proteins are often conformational and, therefore, are more difficult to map.
1872:"Autoantibody epitope mapping by hydrogen-deuterium exchange mass spectrometry at nearly single amino acid residue resolution reveals novel exosites on ADAMTS13 critical for substrate recognition and mechanism of autoimmune thrombotic thrombocytopenic purpura"
109:
that are nearby in the folded 3D structure but distant in the protein sequence. Note that conformational epitopes can include some linear segments. B-cell epitope mapping studies suggest that most interactions between antigens and antibodies, particularly
1656:
Linnebacher, M; et al. (2012). "Clonality characterization of natural epitope-specific antibodies against the tumor-related antigen topoisomerase IIa by peptide chip and proteome analysis: a pilot study with colorectal carcinoma patient samples".
76:. Epitope characterization can also help elucidate the binding mechanism of an antibody and can strengthen intellectual property (patent) protection. Experimental epitope mapping data can be incorporated into robust algorithms to facilitate
434:
are determined in one experiment). The key advantage of this technique is the high sensitivity of MS detection, which means that very little material (hundreds of micrograms or less) is needed.
221:) that can be drugged by multiple competing antibodies. In addition to verifying antibody patentability, epitope mapping data have been used to support broad antibody claims submitted to the
2233:
138:
that are only present when the protein is in its native (properly folded) state, which can make epitope mapping challenging. Epitope mapping has been crucial to the development of
228:
Epitope data have been central to several high-profile legal cases involving disputes over the specific protein regions targeted by therapeutic antibodies. In this regard, the
422:(MS). The cross-linked complex is highly stable and can be exposed to various enzymatic and digestion conditions, allowing many different peptide options for detection. MS or
213:(existing) antibodies. The ability to differentiate between antibodies is particularly important when patenting antibodies against well-validated therapeutic targets (e.g.,
1785:
197:
epitope mapping of antibodies against HER2 revealed a novel epitope (orange spheres). Epitope maps provide supporting data for intellectual property (patent) claims.
2226:
415:
2219:
243:
case hinged on the ability to show that both the Amgen and Sanofi/Regeneron therapeutic antibodies bound to overlapping amino acids on the surface of
222:
1439:
Sandercock, CG; Storz, U (2012). "Antibody specification beyond the target: claiming a later-generation therapeutic antibody by its target epitope".
1903:
Malito, E.; Faleri, A.; Surdo, PL; Veggi, D.; Maruggi, G.; Grassi, E.; Cartocci, E.; Bertoldi, I.; Genovese, A.; Santini, L.; Romagnoli, G. (2013).
381:
Shotgun mutagenesis is a high-throughput approach for mapping the epitopes of mAbs. The shotgun mutagenesis technique begins with the creation of a
2327:
599:
512:
2277:
866:
303:
130:(mAb) development. Epitope mapping can reveal how a mAb exerts its functional effects - for instance, by blocking the binding of a
1337:"Peptide microarray-based identification of Mycobacterium tuberculosis epitope binding to HLA-DRB1*0101, DRB1*1501, and DRB1*0401"
285:
1553:"Cryo-EM structures elucidate neutralizing mechanisms of anti-chikungunya human monoclonal antibodies with therapeutic activity"
1531:
1130:"Mapping the human memory B cell and serum neutralizing antibody responses to dengue virus serotype 4 infection and vaccination"
402:
214:
1179:"Broadly neutralizing antibodies from human survivors target a conserved site in the Ebola virus glycoprotein HR2–MPER region"
166:
2475:
2250:
2267:
326:
2169:"Mapping epitopes with H/D-ex mass spec: ExSAR expands repertoire of technology platform beyond protein characterization"
2312:
2292:
726:"Integral Molecular sizes up Ebola: Membrane protein specialist maps Ebola's binding sites to advance vaccine discovery"
276:
177:) are key targets of drug discovery. Mapping epitopes on these targets can be challenging because of the difficulty in
2422:
450:, provide high-throughput monitoring of antibody binding but lack resolution, especially for conformational epitopes.
2168:
1905:"Defining a protective epitope on factor H binding protein, a key meningococcal virulence factor and vaccine antigen"
677:"Systematic analysis of monoclonal antibodies against Ebola virus GP defines features that contribute to protection"
2470:
426:
techniques are used to detect the amino-acid locations of the labelled cross-linkers and the bound peptides (both
2444:
1049:
725:
367:
361:
237:
2407:
2332:
2205:
2017:
Puchades, C.; Kűkrer, B.; Diefenbach, O.; Sneekes-Vriese, E.; Juraszek, J.; Koudstaal, W.; Apetri, A. (2019).
1228:"Immunization-elicited broadly protective antibody reveals ebolavirus fusion loop as a site of vulnerability"
64:). Identification and characterization of antibody binding sites aid in the discovery and development of new
2357:
2282:
414:
Antibody and antigen are bound to a labeled cross-linker, and complex formation is confirmed by high-mass
135:
102:
2397:
2287:
1779:
321:
202:
190:
131:
1827:
Lo Conte, L; Chothia, C; Janin, J (1999). "The atomic structure of protein-protein recognition sites".
781:
2417:
2211:
2121:
2030:
1916:
1564:
1288:
1084:
958:
813:"Mechanism of binding to Ebola virus glycoprotein by the ZMapp, ZMAb, and MB-003 cocktail antibodies"
178:
271:
2412:
2381:
2259:
151:
127:
123:
1871:
1484:"The biological activity of human CD20 monoclonal antibodies is linked to unique epitopes on CD20"
158:, by determining the antigenic elements (epitopes) that confer long-lasting immunization effects.
2347:
2342:
1999:
1852:
1682:
1638:
1464:
654:
339:
2434:
2149:
2066:
2048:
1991:
1952:
1934:
1844:
1723:
1674:
1630:
1592:
1513:
1505:
1456:
1418:
1366:
1314:
1257:
1208:
1159:
1110:
1027:
976:
924:
842:
706:
646:
595:
572:
518:
508:
419:
2110:"Fructose 1,6-Bisphosphate Aldolase, a Novel Immunogenic Surface Protein on Listeria Species"
2365:
2337:
2180:
2139:
2129:
2056:
2038:
1983:
1942:
1924:
1883:
1836:
1767:
1757:
1713:
1666:
1622:
1582:
1572:
1495:
1448:
1408:
1400:
1356:
1348:
1304:
1296:
1247:
1239:
1198:
1190:
1149:
1141:
1100:
1092:
1017:
1007:
966:
914:
906:
832:
824:
793:
760:
696:
688:
636:
628:
562:
554:
500:
205:(IP) of therapeutic mAbs. Knowledge of the specific binding sites of antibodies strengthens
162:
2201:
1971:
2272:
475:
240:
170:
114:
and protective antibodies (e.g., in vaccines), rely on binding to discontinuous epitopes.
89:
Epitopes are generally divided into two classes: linear and conformational/discontinuous.
1742:
615:
Gershoni, JM; Roitburd-Berman, A; Siman-Tov, DD; Tarnovitski Freund, N; Weiss, Y (2007).
418:
detection. The binding location of the antibody to the antigen can then be identified by
2125:
2034:
1920:
1568:
1292:
1277:"Neutralizing human antibodies prevent Zika virus replication and fetal disease in mice"
1088:
962:
2144:
2109:
2084:
2061:
2018:
1947:
1904:
1587:
1552:
1413:
1388:
1361:
1336:
1309:
1276:
1252:
1227:
1203:
1178:
1154:
1129:
1105:
1072:
1022:
995:
919:
894:
837:
812:
701:
676:
641:
616:
567:
542:
467:
111:
90:
316:
There are several methods available for mapping antibody epitopes on target antigens:
2464:
2369:
2003:
1987:
1802:
632:
443:
439:
194:
31:
1856:
1743:"Functional reconstruction of structurally complex epitopes using CLIPS™ technology"
1686:
1642:
1468:
658:
543:"A high-throughput shotgun mutagenesis approach to mapping B-cell antibody epitopes"
2402:
2242:
343:
147:
65:
27:
19:
1888:
910:
2134:
2019:"Epitope mapping of diverse influenza Hemagglutinin drug candidates using HDX-MS"
1718:
1701:
797:
765:
748:
134:
or by trapping a protein in a non-functional state. Many therapeutic mAbs target
2374:
2304:
1762:
447:
174:
143:
106:
94:
73:
24:
2043:
1972:"Antibody epitope mapping at single residue resolution for unpurified antigens"
1500:
1483:
1243:
971:
946:
692:
504:
461:
2439:
2246:
1670:
1194:
1096:
457:
390:
155:
39:
2052:
1995:
1938:
1509:
749:"B-cell epitope mapping for the design of vaccines and effective diagnostics"
1929:
1577:
996:"An introduction to B-cell epitope mapping and in silico epitope prediction"
371:
210:
78:
2153:
2070:
1956:
1840:
1727:
1678:
1626:
1613:
Bogan, AA; Thorn, KS (1998). "Anatomy of hot spots in protein interfaces".
1596:
1517:
1460:
1422:
1370:
1318:
1261:
1212:
1163:
1114:
1031:
1012:
980:
928:
846:
710:
650:
576:
522:
1848:
1771:
1634:
2184:
1352:
1145:
828:
431:
382:
69:
53:
1300:
895:"Enhancing antibody patent protection using epitope mapping information"
2322:
427:
394:
386:
357:
amino acid resolution, and can therefore pinpoint key epitope residues.
349:
139:
98:
61:
57:
48:
1404:
617:"Epitope mapping: the first step in developing epitope-based vaccines"
558:
34:. Epitope maps provide data for determining mechanism of action (MOA).
2449:
1452:
375:
typically limiting analysis to a small number of amino-acid residues.
233:
206:
83:
2317:
423:
281:
Most methods mentioned are only for antibodies, not B- or T-cells.
244:
229:
46:
is the process of experimentally identifying the binding site, or
209:
and regulatory submissions by distinguishing between current and
16:
Identifying the binding site of an antibody on its target antigen
370:(SDM) can be used to enable epitope mapping. In SDM, systematic
353:
218:
2215:
254:
1073:"Mxra8 is a receptor for multiple arthritogenic alphaviruses"
947:"Rush to protect lucrative antibody patents kicks into gear"
782:"T-cell epitope mapping for the design of powerful vaccines"
393:
mutation (typically an alanine substitution). Hundreds of
126:, epitope mapping is a critical component in therapeutic
201:
Epitope mapping has become prevalent in protecting the
867:"Using epitope mapping to derive more value from mAbs"
1389:"Atomic-level mapping of antibody epitopes on a GPCR"
142:
against prevalent or deadly viral pathogens, such as
379:
High-throughput shotgun mutagenesis epitope mapping.
186:
Importance for intellectual property (IP) protection
2390:
2356:
2303:
2258:
590:Westwood, Olwyn M. R.; Hay, Frank C., eds. (2001).
86:epitopes based on sequence and/or structural data.
23:High-resolution epitope maps of antibodies against
499:. Methods Mol Biol. Vol. 96. pp. 11–20.
594:. Oxford, Oxfordshire: Oxford University Press.
389:, with each clone containing a unique
1909:Proceedings of the National Academy of Sciences
994:Potocnakova, L; Bhide, M; Pulzova, LB (2017).
2227:
1784:: CS1 maint: DOI inactive as of April 2024 (
8:
2173:Genetic Engineering & Biotechnology News
2089:covalx.com/services/epitope-mapping-overview
1054:Genetic Engineering & Biotechnology News
871:Genetic Engineering & Biotechnology News
730:Genetic Engineering & Biotechnology News
780:Ahmad, TA; Eweida, A; El-Sayed, LH (2016).
747:Ahmad, TA; Eweida, A; Sheweita, SA (2016).
2234:
2220:
2212:
348:Also known as overlapping peptide scan or
2204:at the U.S. National Library of Medicine
2143:
2133:
2060:
2042:
1946:
1928:
1887:
1761:
1717:
1586:
1576:
1499:
1412:
1360:
1308:
1251:
1202:
1153:
1104:
1021:
1011:
970:
918:
836:
764:
700:
640:
566:
304:Learn how and when to remove this message
223:United States Patent and Trademark Office
1393:Journal of the American Chemical Society
495:DeLisser, HM (1999). "Epitope mapping".
412:Cross-linking-coupled mass spectrometry.
189:
118:Importance for antibody characterization
18:
2328:Enzyme multiplied immunoassay technique
487:
328:cryogenic electron microscopy (cryo-EM)
93:are formed by a continuous sequence of
1777:
1702:"CD20 antibodies: doing the time warp"
1659:Analytical and Bioanalytical Chemistry
1608:
1606:
893:Deng, X; Storz, U; Doranz, BJ (2018).
366:The molecular biological technique of
1797:
1795:
1434:
1432:
1382:
1380:
1330:
1328:
1043:
1041:
940:
938:
888:
886:
884:
865:Banik, S; Deng, X; Doranz, B (2017).
860:
858:
856:
592:Epitope Mapping: A Practical Approach
7:
1335:Gaseitsiwe, S.; et al. (2010).
670:
668:
536:
534:
532:
1050:"Mapping complex antibody epitopes"
32:shotgun mutagenesis epitope mapping
2278:Ouchterlony double immunodiffusion
1741:Timmerman, P; et al. (2009).
1532:"Amgen Inc. et al v. Sanofi et al"
1275:Sapparapu, G; et al. (2016).
1128:Nivarthi, UK; et al. (2017).
14:
2108:Mendonça, M; et al. (2016).
1482:Teeling, TJ; et al. (2006).
811:Davidson, E; et al. (2015).
161:Complex target antigens, such as
1988:10.4049/jimmunol.202.Supp.131.36
1870:Casina, VC; et al. (2014).
633:10.2165/00063030-200721030-00002
460:
259:
1341:Clinical and Vaccine Immunology
1048:Banik, SSR; Doranz, BJ (2010).
541:Davidson, E; Doranz, B (2014).
1177:Flyak AI; et al. (2018).
1071:Zhang, R; et al. (2018).
1000:Journal of Immunology Research
1:
2268:Chromatin immunoprecipitation
1889:10.1182/blood.V124.21.108.108
1551:Long, F; et al. (2015).
1387:Paes, C; et al. (2009).
1226:Zhao, X; et al. (2017).
911:10.1080/19420862.2017.1402998
724:Dutton, G (January 1, 2016).
385:library of the entire target
2313:Chemiluminescent immunoassay
2293:Counterimmunoelectrophoresis
2167:Flanagan, N (May 15, 2011).
2135:10.1371/journal.pone.0160544
1829:Journal of Molecular Biology
1719:10.1182/blood-2011-04-346700
1615:Journal of Molecular Biology
798:10.1016/j.vacrep.2016.07.002
766:10.1016/j.trivac.2016.04.003
167:G protein-coupled receptors
122:By providing information on
2423:Direct fluorescent antibody
1763:10.2174/1875035400902010056
403:Hydrogen–deuterium exchange
279:. The specific problem is:
2492:
2044:10.1038/s41598-019-41179-0
1803:"Epitope Mapping Services"
1501:10.4049/jimmunol.177.1.362
1244:10.1016/j.cell.2017.04.038
972:10.1038/d41586-018-05273-z
693:10.1016/j.cell.2018.07.033
497:Adhesion Protein Protocols
275:to meet Knowledge (XXG)'s
2445:Total complement activity
1976:The Journal of Immunology
1671:10.1007/s00216-012-5781-5
1195:10.1038/s41564-018-0157-z
1097:10.1038/s41586-018-0121-3
368:site-directed mutagenesis
362:Site-directed mutagenesis
238:Regeneron Pharmaceuticals
2408:Complement fixation test
2206:Medical Subject Headings
1982:(1 Supplement): 131.36.
1750:The Open Vaccine Journal
505:10.1385/1-59259-258-9:11
322:X-ray co-crystallography
179:expressing and purifying
1930:10.1073/pnas.1222845110
1766:(inactive 2024-04-03).
1578:10.1073/pnas.1515558112
438:Other methods, such as
136:conformational epitopes
105:epitopes are formed by
103:Conformational epitopes
30:(GP), determined using
2283:Radial immunodiffusion
1841:10.1006/jmbi.1998.2439
1627:10.1006/jmbi.1998.1843
687:(4). et al.: P938–52.
198:
35:
2476:Antigenic determinant
2398:Diagnostic immunology
2288:Immunoelectrophoresis
1488:Journal of Immunology
753:Trials in Vaccinology
203:intellectual property
193:
22:
2418:Immunohistochemistry
2185:10.1089/gen.31.10.02
1441:Nature Biotechnology
1353:10.1128/CVI.00208-09
1146:10.1128/JVI.02041-16
1013:10.1155/2016/6760830
829:10.1128/JVI.01490-15
675:Saphire, EO (2018).
286:improve this article
2413:Immunocytochemistry
2382:Latex fixation test
2260:Immunoprecipitation
2126:2016PLoSO..1160544M
2035:2019NatSR...9.4735P
1921:2013PNAS..110.3304M
1569:2015PNAS..11213898L
1563:(45): 13898–13903.
1301:10.1038/nature20564
1293:2016Natur.540..443S
1183:Nature Microbiology
1134:Journal of Virology
1089:2018Natur.557..570Z
963:2018Natur.557..623L
945:Ledford, H (2018).
817:Journal of Virology
195:Shotgun mutagenesis
128:monoclonal antibody
124:mechanism of action
2348:Immunofluorescence
2343:Radiobinding assay
2023:Scientific Reports
1807:Integral Molecular
1700:Cragg, MS (2011).
199:
36:
2471:Immunologic tests
2458:
2457:
2435:Skin allergy test
2085:"Epitope Mapping"
1405:10.1021/ja900186n
1399:(20): 6952–6954.
957:(7707): 623–624.
601:978-0-19-963652-5
559:10.1111/imm.12323
514:978-1-59259-258-6
420:mass spectrometry
314:
313:
306:
277:quality standards
268:This article may
163:membrane proteins
2483:
2366:Hemagglutination
2338:Radioimmunoassay
2236:
2229:
2222:
2213:
2189:
2188:
2164:
2158:
2157:
2147:
2137:
2105:
2099:
2098:
2096:
2095:
2081:
2075:
2074:
2064:
2046:
2014:
2008:
2007:
1970:Pan, J. (2019).
1967:
1961:
1960:
1950:
1932:
1915:(9): 3304–3309.
1900:
1894:
1893:
1891:
1867:
1861:
1860:
1835:(5): 2177–2198.
1824:
1818:
1817:
1815:
1813:
1799:
1790:
1789:
1783:
1775:
1765:
1747:
1738:
1732:
1731:
1721:
1697:
1691:
1690:
1653:
1647:
1646:
1610:
1601:
1600:
1590:
1580:
1548:
1542:
1541:
1539:
1538:
1528:
1522:
1521:
1503:
1479:
1473:
1472:
1453:10.1038/nbt.2291
1436:
1427:
1426:
1416:
1384:
1375:
1374:
1364:
1332:
1323:
1322:
1312:
1272:
1266:
1265:
1255:
1223:
1217:
1216:
1206:
1174:
1168:
1167:
1157:
1140:(5): e02041–16.
1125:
1119:
1118:
1108:
1068:
1062:
1061:
1045:
1036:
1035:
1025:
1015:
991:
985:
984:
974:
942:
933:
932:
922:
890:
879:
878:
862:
851:
850:
840:
823:(21): 10982–92.
808:
802:
801:
777:
771:
770:
768:
744:
738:
737:
721:
715:
714:
704:
672:
663:
662:
644:
612:
606:
605:
587:
581:
580:
570:
538:
527:
526:
492:
470:
465:
464:
350:pepscan analysis
309:
302:
298:
295:
289:
263:
262:
255:
173:proteins (e.g.,
2491:
2490:
2486:
2485:
2484:
2482:
2481:
2480:
2461:
2460:
2459:
2454:
2430:Epitope mapping
2386:
2352:
2299:
2273:Immunodiffusion
2254:
2240:
2202:Epitope+mapping
2198:
2193:
2192:
2166:
2165:
2161:
2120:(8): e0160544.
2107:
2106:
2102:
2093:
2091:
2083:
2082:
2078:
2016:
2015:
2011:
1969:
1968:
1964:
1902:
1901:
1897:
1869:
1868:
1864:
1826:
1825:
1821:
1811:
1809:
1801:
1800:
1793:
1776:
1745:
1740:
1739:
1735:
1699:
1698:
1694:
1655:
1654:
1650:
1612:
1611:
1604:
1550:
1549:
1545:
1536:
1534:
1530:
1529:
1525:
1481:
1480:
1476:
1438:
1437:
1430:
1386:
1385:
1378:
1334:
1333:
1326:
1287:(7633): 443–7.
1274:
1273:
1269:
1225:
1224:
1220:
1176:
1175:
1171:
1127:
1126:
1122:
1083:(7706): 570–4.
1070:
1069:
1065:
1047:
1046:
1039:
993:
992:
988:
944:
943:
936:
892:
891:
882:
864:
863:
854:
810:
809:
805:
786:Vaccine Reports
779:
778:
774:
746:
745:
741:
723:
722:
718:
674:
673:
666:
614:
613:
609:
602:
589:
588:
584:
540:
539:
530:
515:
494:
493:
489:
484:
476:Epitope binning
466:
459:
456:
310:
299:
293:
290:
283:
264:
260:
253:
241:PCSK9 inhibitor
188:
120:
91:Linear epitopes
60:(usually, on a
44:epitope mapping
17:
12:
11:
5:
2489:
2487:
2479:
2478:
2473:
2463:
2462:
2456:
2455:
2453:
2452:
2447:
2442:
2437:
2432:
2427:
2426:
2425:
2415:
2410:
2405:
2400:
2394:
2392:
2388:
2387:
2385:
2384:
2379:
2378:
2377:
2362:
2360:
2354:
2353:
2351:
2350:
2345:
2340:
2335:
2330:
2325:
2320:
2315:
2309:
2307:
2301:
2300:
2298:
2297:
2296:
2295:
2290:
2285:
2280:
2270:
2264:
2262:
2256:
2255:
2241:
2239:
2238:
2231:
2224:
2216:
2210:
2209:
2197:
2196:External links
2194:
2191:
2190:
2159:
2100:
2076:
2009:
1962:
1895:
1862:
1819:
1791:
1772:11245/1.309707
1733:
1692:
1648:
1602:
1543:
1523:
1474:
1447:(7): 615–618.
1428:
1376:
1324:
1267:
1238:(5): 891–904.
1218:
1189:(6): 670–677.
1169:
1120:
1063:
1037:
986:
934:
880:
852:
803:
772:
739:
716:
664:
607:
600:
582:
528:
513:
486:
485:
483:
480:
479:
478:
472:
471:
468:Biology portal
455:
452:
446:, and limited
436:
435:
409:
399:
376:
358:
336:
312:
311:
267:
265:
258:
252:
249:
187:
184:
119:
116:
112:autoantibodies
82:prediction of
56:on its target
15:
13:
10:
9:
6:
4:
3:
2:
2488:
2477:
2474:
2472:
2469:
2468:
2466:
2451:
2448:
2446:
2443:
2441:
2438:
2436:
2433:
2431:
2428:
2424:
2421:
2420:
2419:
2416:
2414:
2411:
2409:
2406:
2404:
2401:
2399:
2396:
2395:
2393:
2389:
2383:
2380:
2376:
2373:
2372:
2371:
2370:Hemagglutinin
2367:
2364:
2363:
2361:
2359:
2358:Agglutination
2355:
2349:
2346:
2344:
2341:
2339:
2336:
2334:
2331:
2329:
2326:
2324:
2321:
2319:
2316:
2314:
2311:
2310:
2308:
2306:
2302:
2294:
2291:
2289:
2286:
2284:
2281:
2279:
2276:
2275:
2274:
2271:
2269:
2266:
2265:
2263:
2261:
2257:
2252:
2248:
2244:
2243:Medical tests
2237:
2232:
2230:
2225:
2223:
2218:
2217:
2214:
2207:
2203:
2200:
2199:
2195:
2186:
2182:
2178:
2174:
2170:
2163:
2160:
2155:
2151:
2146:
2141:
2136:
2131:
2127:
2123:
2119:
2115:
2111:
2104:
2101:
2090:
2086:
2080:
2077:
2072:
2068:
2063:
2058:
2054:
2050:
2045:
2040:
2036:
2032:
2028:
2024:
2020:
2013:
2010:
2005:
2001:
1997:
1993:
1989:
1985:
1981:
1977:
1973:
1966:
1963:
1958:
1954:
1949:
1944:
1940:
1936:
1931:
1926:
1922:
1918:
1914:
1910:
1906:
1899:
1896:
1890:
1885:
1881:
1877:
1873:
1866:
1863:
1858:
1854:
1850:
1846:
1842:
1838:
1834:
1830:
1823:
1820:
1812:September 21,
1808:
1804:
1798:
1796:
1792:
1787:
1781:
1773:
1769:
1764:
1759:
1755:
1751:
1744:
1737:
1734:
1729:
1725:
1720:
1715:
1712:(2): 219–20.
1711:
1707:
1703:
1696:
1693:
1688:
1684:
1680:
1676:
1672:
1668:
1665:(1): 227–38.
1664:
1660:
1652:
1649:
1644:
1640:
1636:
1632:
1628:
1624:
1620:
1616:
1609:
1607:
1603:
1598:
1594:
1589:
1584:
1579:
1574:
1570:
1566:
1562:
1558:
1554:
1547:
1544:
1533:
1527:
1524:
1519:
1515:
1511:
1507:
1502:
1497:
1494:(1): 362–71.
1493:
1489:
1485:
1478:
1475:
1470:
1466:
1462:
1458:
1454:
1450:
1446:
1442:
1435:
1433:
1429:
1424:
1420:
1415:
1410:
1406:
1402:
1398:
1394:
1390:
1383:
1381:
1377:
1372:
1368:
1363:
1358:
1354:
1350:
1347:(1): 168–75.
1346:
1342:
1338:
1331:
1329:
1325:
1320:
1316:
1311:
1306:
1302:
1298:
1294:
1290:
1286:
1282:
1278:
1271:
1268:
1263:
1259:
1254:
1249:
1245:
1241:
1237:
1233:
1229:
1222:
1219:
1214:
1210:
1205:
1200:
1196:
1192:
1188:
1184:
1180:
1173:
1170:
1165:
1161:
1156:
1151:
1147:
1143:
1139:
1135:
1131:
1124:
1121:
1116:
1112:
1107:
1102:
1098:
1094:
1090:
1086:
1082:
1078:
1074:
1067:
1064:
1059:
1055:
1051:
1044:
1042:
1038:
1033:
1029:
1024:
1019:
1014:
1009:
1005:
1001:
997:
990:
987:
982:
978:
973:
968:
964:
960:
956:
952:
948:
941:
939:
935:
930:
926:
921:
916:
912:
908:
904:
900:
896:
889:
887:
885:
881:
876:
872:
868:
861:
859:
857:
853:
848:
844:
839:
834:
830:
826:
822:
818:
814:
807:
804:
799:
795:
791:
787:
783:
776:
773:
767:
762:
758:
754:
750:
743:
740:
735:
731:
727:
720:
717:
712:
708:
703:
698:
694:
690:
686:
682:
678:
671:
669:
665:
660:
656:
652:
648:
643:
638:
634:
630:
627:(3): 145–56.
626:
622:
618:
611:
608:
603:
597:
593:
586:
583:
578:
574:
569:
564:
560:
556:
552:
548:
544:
537:
535:
533:
529:
524:
520:
516:
510:
506:
502:
498:
491:
488:
481:
477:
474:
473:
469:
463:
458:
453:
451:
449:
445:
444:phage display
441:
440:yeast display
433:
429:
425:
421:
417:
413:
410:
406:
404:
400:
396:
392:
388:
384:
380:
377:
373:
369:
365:
363:
359:
355:
351:
347:
345:
341:
337:
333:
330:
329:
324:
323:
319:
318:
317:
308:
305:
297:
287:
282:
278:
274:
273:
266:
257:
256:
250:
248:
246:
242:
239:
235:
231:
226:
224:
220:
216:
212:
208:
204:
196:
192:
185:
183:
180:
176:
172:
168:
164:
159:
157:
153:
149:
145:
141:
137:
133:
129:
125:
117:
115:
113:
108:
104:
100:
96:
92:
87:
85:
81:
80:
75:
71:
67:
63:
59:
55:
51:
50:
45:
41:
33:
29:
26:
21:
2429:
2403:Nephelometry
2253:86000–86849)
2176:
2172:
2162:
2117:
2113:
2103:
2092:. Retrieved
2088:
2079:
2026:
2022:
2012:
1979:
1975:
1965:
1912:
1908:
1898:
1879:
1875:
1865:
1832:
1828:
1822:
1810:. Retrieved
1806:
1780:cite journal
1756:(1): 56–67.
1753:
1749:
1736:
1709:
1705:
1695:
1662:
1658:
1651:
1618:
1614:
1560:
1556:
1546:
1535:. Retrieved
1526:
1491:
1487:
1477:
1444:
1440:
1396:
1392:
1344:
1340:
1284:
1280:
1270:
1235:
1231:
1221:
1186:
1182:
1172:
1137:
1133:
1123:
1080:
1076:
1066:
1057:
1053:
1003:
999:
989:
954:
950:
905:(2): 204–9.
902:
898:
874:
870:
820:
816:
806:
789:
785:
775:
756:
752:
742:
733:
729:
719:
684:
680:
624:
620:
610:
591:
585:
553:(1): 13–20.
550:
546:
496:
490:
437:
411:
401:
378:
360:
344:oligopeptide
338:
331:
327:
320:
315:
300:
291:
284:Please help
280:
269:
227:
200:
175:ion channels
169:) and multi-
160:
156:Zika viruses
121:
88:
77:
66:therapeutics
47:
43:
37:
28:glycoprotein
2375:Coombs test
2305:Immunoassay
2029:(1): 4735.
1882:(21): 108.
448:proteolysis
288:if you can.
144:chikungunya
107:amino acids
95:amino acids
74:diagnostics
2465:Categories
2440:Patch test
2247:immunology
2094:2017-02-23
1621:(1): 1–9.
1537:2017-07-23
1060:(2): 25–8.
547:Immunology
482:References
391:amino acid
294:March 2024
40:immunology
2333:RAST test
2053:2045-2322
2004:255732819
1996:0022-1767
1939:0027-8424
1510:0022-1767
792:: 13–22.
759:: 71–83.
372:mutations
346:scanning.
211:prior art
79:in silico
2245:used in
2154:27489951
2114:PLOS ONE
2071:30894620
1957:23396847
1857:20154946
1728:21757627
1687:33847079
1679:22349330
1643:11014160
1597:26504196
1518:16785532
1469:52810327
1461:22781681
1423:19453194
1371:19864486
1319:27819683
1262:28525756
1213:29736037
1164:28031369
1115:29769725
1032:28127568
1006:: 1–11.
981:29844545
929:29120697
847:26311869
711:30096313
659:29506607
651:17516710
621:BioDrugs
577:24854488
523:10098119
454:See also
432:paratope
383:mutation
364:mapping.
270:require
140:vaccines
70:vaccines
54:antibody
52:, of an
2323:ELISpot
2145:4973958
2122:Bibcode
2062:6427009
2031:Bibcode
1948:3587270
1917:Bibcode
1849:9925793
1635:9653027
1588:4653152
1565:Bibcode
1414:2943208
1362:2812096
1310:5583716
1289:Bibcode
1253:5803079
1204:6030461
1155:5309932
1106:5970976
1085:Bibcode
1023:5227168
959:Bibcode
920:5825199
838:4621129
702:6102396
642:7100438
568:4137951
428:epitope
395:plasmid
387:antigen
342:-based
272:cleanup
251:Methods
207:patents
171:subunit
165:(e.g.,
99:protein
62:protein
58:antigen
49:epitope
2450:MELISA
2208:(MeSH)
2179:(10).
2152:
2142:
2069:
2059:
2051:
2002:
1994:
1955:
1945:
1937:
1855:
1847:
1726:
1685:
1677:
1641:
1633:
1595:
1585:
1516:
1508:
1467:
1459:
1421:
1411:
1369:
1359:
1317:
1307:
1281:Nature
1260:
1250:
1211:
1201:
1162:
1152:
1113:
1103:
1077:Nature
1030:
1020:
979:
951:Nature
927:
917:
845:
835:
709:
699:
657:
649:
639:
598:
575:
565:
521:
511:
405:(HDX).
234:Sanofi
154:, and
148:dengue
132:ligand
84:B-cell
72:, and
2391:Other
2318:ELISA
2000:S2CID
1876:Blood
1853:S2CID
1746:(PDF)
1706:Blood
1683:S2CID
1639:S2CID
1465:S2CID
877:(15).
655:S2CID
424:MS/MS
416:MALDI
340:Array
245:PCSK9
230:Amgen
152:Ebola
97:in a
25:Ebola
2150:PMID
2067:PMID
2049:ISSN
1992:ISSN
1953:PMID
1935:ISSN
1845:PMID
1814:2018
1786:link
1724:PMID
1675:PMID
1631:PMID
1593:PMID
1557:PNAS
1514:PMID
1506:ISSN
1457:PMID
1419:PMID
1367:PMID
1315:PMID
1258:PMID
1232:Cell
1209:PMID
1160:PMID
1111:PMID
1028:PMID
1004:2016
977:PMID
925:PMID
899:mAbs
843:PMID
736:(1).
707:PMID
681:Cell
647:PMID
596:ISBN
573:PMID
519:PMID
509:ISBN
430:and
354:CD20
325:and
219:CD20
217:and
2251:CPT
2181:doi
2140:PMC
2130:doi
2057:PMC
2039:doi
1984:doi
1980:202
1943:PMC
1925:doi
1913:110
1884:doi
1880:124
1837:doi
1833:285
1768:hdl
1758:doi
1714:doi
1710:118
1667:doi
1663:403
1623:doi
1619:280
1583:PMC
1573:doi
1561:112
1496:doi
1492:177
1449:doi
1409:PMC
1401:doi
1397:131
1357:PMC
1349:doi
1305:PMC
1297:doi
1285:540
1248:PMC
1240:doi
1236:169
1199:PMC
1191:doi
1150:PMC
1142:doi
1101:PMC
1093:doi
1081:557
1018:PMC
1008:doi
967:doi
955:557
915:PMC
907:doi
833:PMC
825:doi
794:doi
761:doi
697:PMC
689:doi
685:174
637:PMC
629:doi
563:PMC
555:doi
551:143
501:doi
232:v.
215:PD1
38:In
2467::
2177:31
2175:.
2171:.
2148:.
2138:.
2128:.
2118:11
2116:.
2112:.
2087:.
2065:.
2055:.
2047:.
2037:.
2025:.
2021:.
1998:.
1990:.
1978:.
1974:.
1951:.
1941:.
1933:.
1923:.
1911:.
1907:.
1878:.
1874:.
1851:.
1843:.
1831:.
1805:.
1794:^
1782:}}
1778:{{
1752:.
1748:.
1722:.
1708:.
1704:.
1681:.
1673:.
1661:.
1637:.
1629:.
1617:.
1605:^
1591:.
1581:.
1571:.
1559:.
1555:.
1512:.
1504:.
1490:.
1486:.
1463:.
1455:.
1445:30
1443:.
1431:^
1417:.
1407:.
1395:.
1391:.
1379:^
1365:.
1355:.
1345:17
1343:.
1339:.
1327:^
1313:.
1303:.
1295:.
1283:.
1279:.
1256:.
1246:.
1234:.
1230:.
1207:.
1197:.
1185:.
1181:.
1158:.
1148:.
1138:91
1136:.
1132:.
1109:.
1099:.
1091:.
1079:.
1075:.
1056:.
1052:.
1040:^
1026:.
1016:.
1002:.
998:.
975:.
965:.
953:.
949:.
937:^
923:.
913:.
903:10
901:.
897:.
883:^
875:37
873:.
869:.
855:^
841:.
831:.
821:89
819:.
815:.
788:.
784:.
755:.
751:.
734:36
732:.
728:.
705:.
695:.
683:.
679:.
667:^
653:.
645:.
635:.
625:21
623:.
619:.
571:.
561:.
549:.
545:.
531:^
517:.
507:.
442:,
247:.
225:.
150:,
146:,
101:.
68:,
42:,
2368:/
2249:(
2235:e
2228:t
2221:v
2187:.
2183::
2156:.
2132::
2124::
2097:.
2073:.
2041::
2033::
2027:9
2006:.
1986::
1959:.
1927::
1919::
1892:.
1886::
1859:.
1839::
1816:.
1788:)
1774:.
1770::
1760::
1754:2
1730:.
1716::
1689:.
1669::
1645:.
1625::
1599:.
1575::
1567::
1540:.
1520:.
1498::
1471:.
1451::
1425:.
1403::
1373:.
1351::
1321:.
1299::
1291::
1264:.
1242::
1215:.
1193::
1187:3
1166:.
1144::
1117:.
1095::
1087::
1058:3
1034:.
1010::
983:.
969::
961::
931:.
909::
849:.
827::
800:.
796::
790:6
769:.
763::
757:5
713:.
691::
661:.
631::
604:.
579:.
557::
525:.
503::
332:.
307:)
301:(
296:)
292:(
236:/
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
