IgE is a key mediator in allergic diseases. However, in strong contrast to other antibody isotypes, many details of the composition of the human IgE repertoire are poorly defined. The low levels of human IgE in the circulation and the rarity of IgE-producing B cells are important reasons for this lack of knowledge. In this review, we summarize the current knowledge on these repertoires both in terms of their complexity and activity, i.e. knowledge which despite the difficulties encountered when studying the molecular details of human IgE has been acquired in recent years. We also take a look at likely future developments, for instance through improvements in sequencing technology and methodology that allow the isolation of additional allergen-specific human antibodies mimicking IgE, as this certainly will support our understanding of human IgE in the context of human disease in the years to come.

1.
Flöistrup H, Swartz J, Bergström A, et al: Allergic disease and sensitization in Steiner school children. J Allergy Clin Immunol 2006;117:59-66.
2.
Larche M, Akdis CA, Valenta R: Immunological mechanisms of allergen-specific immunotherapy. Nat Rev Immunol 2006;6:761-771.
3.
Ishizaka K, Ishizaka T: Identification of γE-antibodies as a carrier of reaginic activity. J Immunol 1967;99:1187-1198.
4.
Johansson SG: The history of IgE: from discovery to 2010. Curr Allergy Asthma Rep 2011;11:173-177.
5.
Stanworth DR, Humphrey JH, Bennich H, Johansson SGO: Specific inhibition of the Prausnitz-Küstner reaction by an atypical human myeloma protein. Lancet 1967;2:330-332.
6.
Wide L, Bennich H, Johansson SG: Diagnosis of allergy by an in-vitro test for allergen antibodies. Lancet 1967;2:1105-1107.
7.
Fang KS, Vitale M, Fehlner P, King TP: cDNA cloning and primary structure of a white-face hornet venom allergen, antigen 5. Proc Natl Acad Sci USA 1988;85:895-899.
8.
Chua KY, Stewart GA, Thomas WR, et al: Sequence analysis of cDNA coding for a major house dust mite allergen, Der p 1. Homology with cysteine proteases. J Exp Med 1988;167:175-182.
9.
Thomas WR, Stewart GA, Simpson RJ, et al: Cloning and expression of DNA coding for the major house dust mite allergen Der p 1 in Escherichia coli. Int Arch Allergy Appl Immunol 1988;85:127-129.
10.
Breiteneder H, Pettenburger K, Bito A, et al: The gene coding for the major birch pollen allergen Betv1, is highly homologous to a pea disease resistance response gene. EMBO J 1989;8:1935-1938.
11.
Mari A, Scala E: Allergome: a unifying platform. Arb Paul Ehrlich Inst Bundesamt Sera Impfstoffe Frankf AM 2006;95:29-39.
12.
Radauer C, Bublin M, Wagner S, Mari A, Breiteneder H: Allergens are distributed into few protein families and possess a restricted number of biochemical functions. J Allergy Clin Immunol 2008;121:847-852.
13.
Chapman MD, Pomés A, Breiteneder H, Ferreira F: Nomenclature and structural biology of allergens. J Allergy Clin Immunol 2007;119:414-420.
14.
Valenta R, Lidholm J, Niederberger V, et al: The recombinant allergen-based concept of component-resolved diagnostics and immunotherapy (CRD and CRIT). Clin Exp Allergy 1999;29:896-904.
15.
Heiss S, Mahler V, Steiner R, et al: Component-resolved diagnosis (CRD) of type I allergy with recombinant grass and tree pollen allergens by skin testing. J Invest Dermatol 1999;113:830-837.
16.
Hiller R, Laffer S, Harwanegg C, et al: Microarrayed allergen molecules: diagnostic gatekeepers for allergy treatment. FASEB J 2002;16:414-416.
17.
Valenta R, Linhart B, Swoboda I, Niederberger V: Recombinant allergens for allergen-specific immunotherapy: 10 years anniversary of immunotherapy with recombinant allergens. Allergy 2011;66:775-783.
18.
Xu JL, Davis MM: Diversity in the CDR3 region of V(H) is sufficient for most antibody specificities. Immunity 2000;13:37-45.
19.
Venet S, Ravn U, Buatois V, et al: Transferring the characteristics of naturally occurring and biased antibody repertoires to human antibody libraries by trapping CDRH3 sequences. PLoS One 2012;7:e43471.
20.
Gadermaier E, Flicker S, Lupinek C, Steinberger P, Valenta R: Determination of allergen specificity by heavy chains in grass pollen allergen-specific IgE antibodies. J Allergy Clin Immunol 2013;131:1185-1193.
21.
Lefranc MP, Giudicelli V, Ginestoux C, et al: IMGT®, the international ImMunoGeneTics information system®. Nucl Acids Res 2009;37:D1006-D1012.
22.
Cook GP, Tomlinson IM, Walter G, et al: A map of the human immunoglobulin VH locus completed by analysis of the telomeric region of chromosome 14q. Nat Genet 1994;7:162-168.
23.
Corbett SJ, Tomlinson IM, Sonnhammer ELL, Buck D, Winter G: Sequence of the human immunoglobulin diversity (D) segment locus: a systematic analysis provides no evidence for the use of DIR segments, inverted D segments, ‘minor' D segments or D-D recombination. J Mol Biol 1997;270:587-597.
24.
Ravetch JV, Siebenlist U, Korsmeyer S, Waldmann T, Leder P: Structure of the human immunoglobulin mu locus: characterization of embryonic and rearranged J and D genes. Cell 1981;27:583-591.
25.
Tomlinson IM, Walter G, Marks JD, Llewelyn MB, Winter G: The repertoire of human germline VH sequences reveals about fifty groups of VH segments with different hypervariable loops. J Mol Biol 1992;227:776-798.
26.
Kidd MJ, Chen Z, Wang Y, et al: The inference of phased haplotypes for the immunoglobulin H chain V region gene loci by analysis of VDJ gene rearrangements. J Immunol 2012;188:1333-1340.
27.
Boyd SD, Gaëta BA, Jackson KJ, et al: Individual variation in the germline Ig gene repertoire inferred from variable region gene rearrangements. J Immunol 2010;184:6986-6992.
28.
Watson CT, Breden F: The immunoglobulin heavy chain locus: genetic variation, missing data, and implications for human disease. Genes Immun 2012;13:363-373.
29.
Barrios Y, Jirholt P, Ohlin M: Length of the antibody heavy chain complementarity determining region 3 as a specificity-determining factor. J Mol Recognit 2004;17:332-338.
30.
Cupps TR, Goldsmith PK, Volkman DJ, et al: Activation of human peripheral blood B cells following immunization with hepatitis B surface antigen vaccine. Cell Immunol 1984;86:145-154.
31.
Falkoff RJ, Zhu LP, Fauci AS: The relationship between immunization and circulating antigen-specific plaque-forming cells. Cell Immunol 1983;78:392-399.
32.
Wrammert J, Smith K, Miller J, et al: Rapid cloning of high-affinity human monoclonal antibodies against influenza virus. Nature 2008;453:667-671.
33.
Poulsen TR, Meijer PJ, Jensen A, Nielsen LS, Andersen PS: Kinetic, affinity, and diversity limits of human polyclonal antibody responses against tetanus toxoid. J Immunol 2007;179:3841-3850.
34.
Snow RE, Chapman CJ, Frew AJ, Holgate ST, Stevenson FK: Pattern of usage and somatic hypermutation in the V(H)5 gene segments of a patient with asthma: implications for IgE. Eur J Immunol 1997;27:162-170.
35.
Snow RE, Djukanovic R, Stevenson FK: Analysis of immunoglobulin E VH transcripts in a bronchial biopsy of an asthmatic patient confirms bias towards VH5, and indicates local clonal expansion, somatic mutation and isotype switch events. Immunology 1999;98:646-651.
36.
Coker HA, Harries HE, Banfield GK, et al: Biased use of VH5 IgE-positive B cells in the nasal mucosa in allergic rhinitis. J Allergy Clin Immunol 2005;116:445-452.
37.
Edwards MR, Brouwer W, Choi CH, et al: Analysis of IgE antibodies from a patient with atopic dermatitis: biased V gene usage and evidence for polyreactive IgE heavy chain complementarity-determining region 3. J Immunol 2002;168:6305-6313.
38.
Janezic A, Chapman CJ, Snow RE, et al: Immunogenetic analysis of the heavy chain variable regions of IgE from patients allergic to peanuts. J Allergy Clin Immunol 1998;101:391-396.
39.
Wang Y, Jackson KJ, Chen Z, et al: IgE sequences in individuals living in an area of endemic parasitism show little mutational evidence of antigen selection. Scand J Immunol 2011;73:496-504.
40.
Dahlke I, Nott DJ, Ruhno J, Sewell WA, Collins AM: Antigen selection in the IgE response of allergic and nonallergic individuals. J Allergy Clin Immunol 2006;117:1477-1483.
41.
Davies JM, Platts-Mills TA, Aalberse RC: The enigma of IgE+ B-cell memory in human subjects. J Allergy Clin Immunol 2013;131:972-976.
42.
Levin M, Ohlin M: Inconclusive evidence for or against positive antigen selection in the shaping of human IgE repertoires - a call for new approaches. Int Arch Allergy Immunol 2013;161:122-126.
43.
Davies JM, O'Hehir RE: VH gene usage in immunoglobulin E responses of seasonal rhinitis patients allergic to grass pollen is oligoclonal and antigen driven. Clin Exp Allergy 2004;34:429-436.
44.
Kerzel S, Rogosch T, Struecker B, Maier RF, Zemlin M: IgE transcripts in the circulation of allergic children reflect a classical antigen-driven B cell response and not a superantigen-like activation. J Immunol 2010;185:2253-2260.
45.
Pratt E, Collins AM, Sewell WA, Harvey RJ: Antigen selection in IgE antibodies from individuals with chronic rhinosinusitis with nasal polyps. Am J Rhinol Allergy 2010;24:416-421.
46.
MacDonald CM, Boursier L, D'Cruz DP, Dunn-Walters DK, Spencer J: Mathematical analysis of antigen selection in somatically mutated immunoglobulin genes associated with autoimmunity. Lupus 2010;19:1161-1170.
47.
Coker HA, Durham SR, Gould HJ: Local somatic hypermutation and class switch recombination in the nasal mucosa of allergic rhinitis patients. J Immunol 2003;171:5602-5610.
48.
Gould HJ, Takhar P, Harries HE, Durham SR, Corrigan CJ: Germinal-centre reactions in allergic inflammation. Trends Immunol 2006;27:446-452.
49.
Gevaert P, Nouri-Aria KT, Wu H, et al: Local receptor revision and class switching to IgE in chronic rhinosinusitis with nasal polyps. Allergy 2013;68:55-63.
50.
Takhar P, Corrigan CJ, Smurthwaite L, et al: Class switch recombination to IgE in the bronchial mucosa of atopic and nonatopic patients with asthma. J Allergy Clin Immunol 2007;119:213-218.
51.
Takhar P, Smurthwaite L, Coker HA, et al: Allergen drives class switching to IgE in the nasal mucosa in allergic rhinitis. J Immunol 2005;174:5024-5032.
52.
KleinJan A, Vinke JG, Severijnen LW, Fokkens WJ: Local production and detection of (specific) IgE in nasal B-cells and plasma cells of allergic rhinitis patients. Eur Respir J 2000;15:491-497.
53.
Rondón C, Romero JJ, López S, et al: Local IgE production and positive nasal provocation test in patients with persistent nonallergic rhinitis. J Allergy Clin Immunol 2007;119:899-905.
54.
Levin M, Tan LW, Baker L, et al: Diversity of IgE-encoding transcripts in sinus mucosa of subjects diagnosed with non-allergic fungal eosinophilic sinusitis. Clin Exp Allergy 2011;41:811-820.
55.
Smurthwaite L, Walker SN, Wilson DR, et al: Persistent IgE synthesis in the nasal mucosa of hay fever patients. Eur J Immunol 2001;31:3422-3431.
56.
Karpas A, Dremucheva A, Czepulkowski BH: A human myeloma cell line suitable for the generation of human monoclonal antibodies. Proc Natl Acad Sci USA 2001;98:1799-1804.
57.
Traggiai E, Becker S, Subbarao K, et al: An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirus. Nat Med 2004;10:871-875.
58.
Meijer PJ, Andersen PS, Haahr Hansen M, et al: Isolation of human antibody repertoires with preservation of the natural heavy and light chain pairing. J Mol Biol 2006;358:764-772.
59.
Kwakkenbos MJ, Diehl SA, Yasuda E, et al: Generation of stable monoclonal antibody-producing B cell receptor-positive human memory B cells by genetic programming. Nat Med 2010;16:123-128.
60.
Aalberse RC, Crameri R: IgE-binding epitopes: a reappraisal. Allergy 2011;66:1261-1274.
61.
Horst A, Hunzelmann N, Arce S, et al: Detection and characterization of plasma cells in peripheral blood: correlation of IgE+ plasma cell frequency with IgE serum titre. Clin Exp Immunol 2002;130:370-378.
62.
Eckl-Dorna J, Niederberger V: What is the source of serum allergen-specific IgE? Curr Allergy Asthma Rep 2013;13:281-287.
63.
Visco V, Dolecek C, Denépoux S, et al: Human IgG monoclonal antibodies that modulate the binding of specific IgE to birch pollen Bet v 1. J Immunol 1996;157:956-962.
64.
van de Veen W, de Jong M, Stanic B, et al: Phenotypic and functional characterization of human allergen-specific memory B cells (abstract 54). EAACI-WAO Congress, Milan, 2013.
65.
James LK, Bowen H, Calvert RA, et al: Allergen specificity of IgG4-expressing B cells in patients with grass pollen allergy undergoing immunotherapy. J Allergy Clin Immunol 2012;130:663-670.
66.
Patil SU, Ogunniyi AO, Kubala S: Induction of antigen-specific B cells using novel tetramer-based approach occurs early during peanut oral immunotherapy (abstract 1291). EAACI-WAO Congress, Milan, 2013.
67.
McCafferty J, Griffiths AD, Winter G, Chiswell DJ: Phage antibodies: filamentous phage displaying antibody variable domains. Nature 1990;348:552-554.
68.
Smith GP: Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science 1985;228:1315-1317.
69.
Burton DR, Barbas CF 3rd, Persson MA, et al: A large array of human monoclonal antibodies to type 1 human immunodeficiency virus from combinatorial libraries of asymptomatic seropositive individuals. Proc Natl Acad Sci USA 1991;88:10134-10137.
70.
Benichou J, Ben-Hamo R, Louzoun Y, Efroni S: Rep-Seq: uncovering the immunological repertoire through next-generation sequencing. Immunology 2012;135:183-191.
71.
Saggy I, Wine Y, Shefet-Carasso L, et al: Antibody isolation from immunized animals: comparison of phage display and antibody discovery via V gene repertoire mining. Protein Eng Des Sel 2012;25:539-549.
72.
Derda R, Tang SK, Li SC, et al: Diversity of phage-displayed libraries of peptides during panning and amplification. Molecules 2011;16:1776-1803.
73.
Matochko WL, Chu K, Jin B, et al: Deep sequencing analysis of phage libraries using Illumina platform. Methods 2012;58:47-55.
74.
Steinberger P, Kraft D, Valenta R: Construction of a combinatorial IgE library from an allergic patient. Isolation and characterization of human IgE Fabs with specificity for the major timothy grass pollen allergen, Phl p 5. J Biol Chem 1996;271:10967-10972.
75.
Hecker J, Diethers A, Schulz D, et al: An IgE epitope of Bet v 1 and fagales PR10 proteins as defined by a human monoclonal IgE. Allergy 2012;67:1530-1537.
76.
Persson H, Karbalaei Sadegh M, Greiff L, Ohlin M: Delineating the specificity of an IgE-encoding transcriptome. J Allergy Clin Immunol 2007;120:1186-1192.
77.
Flicker S, Steinberger P, Ball T, et al: Spatial clustering of the IgE epitopes on the major timothy grass pollen allergen Phl p 1: importance for allergenic activity. J Allergy Clin Immunol 2006;117:1336-1343.
78.
Levin M, Rydnert F, Källström E, et al: Phl p 1-specific human monoclonal IgE and design of a hypoallergenic group 1 grass pollen allergen fragment. J Immunol 2013;191:551-560.
79.
Persson H, Flicker S, Karbalaei Sadegh M, et al: A common idiotype in IgE and its relation to recognition of the grass pollen allergen Phl p 2. Mol Immunol 2008;45:2715-2720.
80.
Flicker S, Steinberger P, Norderhaug L, et al: Conversion of grass pollen allergen-specific human IgE into a protective IgG1 antibody. Eur J Immunol 2002;32:2156-2162.
81.
Padavattan S, Flicker S, Schirmer T, et al: High-affinity IgE recognition of a conformational epitope of the major respiratory allergen Phl p 2 as revealed by X-ray crystallography. J Immunol 2009;182:2141-2151.
82.
Flicker S, Vrtala S, Steinberger P, et al: A human monoclonal IgE antibody defines a highly allergenic fragment of the major timothy grass pollen allergen, Phl p 5: molecular, immunological, and structural characterization of the epitope-containing domain. J Immunol 2000;165:3849-3859.
83.
Andréasson U, Flicker S, Lindstedt M, et al: The human IgE-encoding transcriptome to assess antibody repertoires and repertoire evolution. J Mol Biol 2006;362:212-227.
84.
Persson J, Augustsson P, Laurell T, Ohlin M: Acoustic microfluidic chip technology to facilitate automation of phage display selection. FEBS J 2008;275:5657-5666.
85.
Madritsch C, Flicker S, Scheiblhofer S, et al: Recombinant monoclonal human immunoglobulin E to investigate the allergenic activity of major grass pollen allergen Phl p 5. Clin Exp Allergy 2011;41:270-280.
86.
Hecker J, Diethers A, Etzold S, et al: Generation and epitope analysis of human monoclonal antibody isotypes with specificity for the timothy grass major allergen Phl p 5a. Mol Immunol 2011;48:1236-1244.
87.
Christensen LH, Riise E, Bang L, Zhang C, Lund K: Isoallergen variations contribute to the overall complexity of effector cell degranulation: effect mediated through differentiated IgE affinity. J Immunol 2010;184:4966-4972.
88.
Christensen LH, Holm J, Lund G, Riise E, Lund K: Several distinct properties of the IgE repertoire determine effector cell degranulation in response to allergen challenge. J Allergy Clin Immunol 2008;122:298-304.
89.
Niemi M, Jylha S, Laukkanen ML, et al: Molecular interactions between a recombinant IgE antibody and the β-lactoglobulin allergen. Structure 2007;15:1413-1421.
90.
Jylhä S, Makinen-Kiljunen S, Haahtela T, et al: Selection of recombinant IgE antibodies binding the β-lactoglobulin allergen in a conformation-dependent manner. J Immunol Methods 2009;350:63-70.
91.
Laukkanen ML, Mäkinen-Kiljunen S, Isoherranen K, et al: Hevein-specific recombinant IgE antibodies from human single-chain antibody phage display libraries. J Immunol Methods 2003;278:271-281.
92.
Yamada M, Wasserman R, Reichard BA, et al: Preferential utilization of specific immunoglobulin heavy chain diversity and joining segments in adult human peripheral blood B lymphocytes. J Exp Med 1991;173:395-407.
93.
Wu TT, Johnson G, Kabat EA: Length distribution of CDRH3 in antibodies. Proteins 1993;16:1-7.
94.
Souto-Carneiro MM, Sims GP, Girschik H, Lee J, Lipsky PE: Developmental changes in the human heavy chain CDR3. J Immunol 2005;175:7425-7436.
95.
Köhler G, Milstein C: Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 1975;256:495-497.
96.
Böttcher I, Hämmerling G: Continuous production of monoclonal mouse IgE antibodies with known allergenic specificity by a hybrid cell line. Nature 1978;275:761-762.
97.
Liu FT, Bohn JW, Ferry EL, et al: Monoclonal dinitrophenyl-specific murine IgE antibody: preparation, isolation, and characterization. J Immunol 1980;124:2728-2737.
98.
Rudolph AK, Burrows PD, Wabl MR: Thirteen hybridomas secreting hapten-specific immunoglobulin E from mice with Iga or Igb heavy chain haplotype. Eur J Immunol 1981;11:527-529.
99.
Larrick JW, Danielsson L, Brenner CA, et al: Rapid cloning of rearranged immunoglobulin genes from human hybridoma cells using mixed primers and the polymerase chain reaction. Biochem Biophys Res Commun 1989;160:1250-1256.
100.
Li ZD, Yeh M: Construction and diversity analysis of a murine IgE phage surface display library. Cell Res 1997;7:161-170.
101.
Gritzmacher CA, Liu FT: Expression of a recombinant murine IgE in transfected myeloma cells. J Immunol 1987;138:324-329.
102.
Boulianne GL, Hozumi N, Shulman MJ: Production of functional chimaeric mouse/human antibody. Nature 1984;312:643-646.
103.
Morrison SL, Johnson MJ, Herzenberg LA, Oi VT: Chimeric human antibody molecules: mouse antigen-binding domains with human constant region domains. Proc Natl Acad Sci USA 1984;81:6851-6855.
104.
Neuberger MS, Williams GT, Mitchell EB, et al: A hapten-specific chimaeric IgE antibody with human physiological effector function. Nature 1985;314:268-270.
105.
Schuurman J, Perdok GJ, Lourens TE, et al: Production of a mouse/human chimeric IgE monoclonal antibody to the house dust mite allergen Der p 2 and its use for the absolute quantification of allergen-specific IgE. J Allergy Clin Immunol 1997;99:545-550.
106.
Rodin DV, Kolesnikov VA, Srdiuk OV, et al: Synthesis of chimeric IgE in vivo after ballistic transfection of immunoglobulin genes in various mouse tissues. Mol Biol (Mosk) 2000;34:18-23.
107.
Furtado PB, McElveen JE, Gough L, et al: The production and characterisation of a chimaeric human IgE antibody, recognising the major mite allergen Der p 1, and its chimaeric human IgG1 anti-idiotype. Mol Pathol 2002;55:315-324.
108.
Jakobsen CG, Bodtger U, Kristensen P, Poulsen LK, Roggen EL: Isolation of high-affinity human IgE and IgG antibodies recognising Bet v 1 and Humicola lanuginosa lipase from combinatorial phage libraries. Mol Immunol 2004;41:941-953.
109.
Geyer CR, McCafferty J, Dübel S, Bradbury AR, Sidhu SS: Recombinant antibodies and in vitro selection technologies. Methods Mol Biol 2012;901:11-32.
110.
de Lalla C, Tamborini E, Longhi R, et al: Human recombinant antibody fragments specific for a rye-grass pollen allergen: characterization and potential applications. Mol Immunol 1996;33:1049-1058.
111.
Braren I, Blank S, Seismann H, et al: Generation of human monoclonal allergen-specific IgE and IgG antibodies from synthetic antibody libraries. Clin Chem 2007;53:837-844.
112.
Pomés A: Relevant B cell epitopes in allergic disease. Int Arch Allergy Immunol 2010;152:1-11.
113.
Gieras A, Cejka P, Blatt K, et al: Mapping of conformational IgE epitopes with peptide-specific monoclonal antibodies reveals simultaneous binding of different IgE antibodies to a surface patch on the major birch pollen allergen, Bet v 1. J Immunol 2011;186:5333-5344.
114.
Geysen HM, Rodda SJ, Mason TJ: A priori delineation of a peptide which mimics a discontinuous antigenic determinant. Mol Immunol 1986;23:709-715.
115.
Meloen RH, Puijk WC, Slootstra JW: Mimotopes: realization of an unlikely concept. J Mol Recogn 2000;13:352-359.
116.
Devlin JJ, Panganiban LC, Devlin PE: Random peptide libraries: a source of specific protein binding molecules. Science 1990;249:404-406.
117.
Scott JK, Smith GP: Searching for peptide ligands with an epitope library. Science 1990;249:386-390.
118.
Tribbick G: Multipin peptide libraries for antibody and receptor epitope screening and characterization. J Immunol Methods 2002;267:27-35.
119.
Negi SS, Braun W: Automated detection of conformational epitopes using phage display peptide sequences. Bioinform Biol Insights 2009;3:71-81.
120.
Dall'Antonia F, Gieras A, Devanaboyina SC, Valenta R, Keller W: Prediction of IgE-binding epitopes by means of allergen surface comparison and correlation to cross-reactivity. J Allergy Clin Immunol 2011;128:872-879.e8.
121.
Mirza O, Henriksen A, Ipsen H, et al: Dominant epitopes and allergic cross-reactivity: complex formation between a Fab fragment of a monoclonal murine IgG antibody and the major allergen from birch pollen Bet v 1. J Immunol 2000;165:331-338.
122.
Padavattan S, Schirmer T, Schmidt M, et al: Identification of a B-cell epitope of hyaluronidase, a major bee venom allergen, from its crystal structure in complex with a specific Fab. J Mol Biol 2007;368:742-752.
123.
Li M, Gustchina A, Alexandratos J, et al: Crystal structure of a dimerized cockroach allergen Bla g 2 complexed with a monoclonal antibody. J Biol Chem 2008;283:22806-22814.
124.
Valenta R, Kraft D: Recombinant allergen molecules: tools to study effector cell activation. Immunol Rev 2001;179:119-127.
125.
Chruszcz M, Pomés A, Glesner J, et al: Molecular determinants for antibody binding on group 1 house dust mite allergens. J Biol Chem 2012;287:7388-7398.
126.
Boström J, Yu SF, Kan D, et al: Variants of the antibody herceptin that interact with HER2 and VEGF. Science 2009;323:1610-1614.
127.
Ohlin M, Owman H, Mach M, Borrebaeck CAK: Light chain shuffling of a high affinity antibody results in a drift in epitope recognition. Mol Immunol 1996;33:47-56.
128.
Poulsen TR, Jensen A, Haurum JS, Andersen PS: Limits for antibody affinity maturation and repertoire diversification in hypervaccinated humans. J Immunol 2011;187:4229-4235.
129.
Valenta R, Lidholm J, Niederberger V, et al: The recombinant allergen-based concept of component-resolved diagnostics and immunotherapy (CRD and CRIT). Clin Exp Allergy 1999;29:896-904.
130.
Melioli G, Marcomini L, Agazzi A, et al: The IgE repertoire in children and adolescents resolved at component level: a cross-sectional study. Pediatr Allergy Immunol 2012;23:433-440.
131.
Scala E, Alessandri C, Bernardi ML, et al: Cross-sectional survey on immunoglobulin E reactivity in 23,077 subjects using an allergenic molecule-based microarray detection system. Clin Exp Allergy 2010;40:911-921.
132.
Scala E, Alessandri C, Palazzo P, et al: IgE recognition patterns of profilin, PR-10, and tropomyosin panallergens tested in 3,113 allergic patients by allergen microarray-based technology. Plos One 2011;6:e24912.
133.
De Knop KJ, Verweij MM, Grimmelikhuijsen M, et al: Age-related sensitization profiles for hazelnut (Corylus avellana) in a birch-endemic region. Pediatr Allergy Immunol 2011;22:e139-e149.
134.
Asher MI, Montefort S, Björkstén B, et al: Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys. Lancet 2006;368:733-743.
135.
Kulig M, Bergmann R, Klettke U, et al: Natural course of sensitization to food and inhalant allergens during the first 6 years of life. J Allergy Clin Immunol 1999;103:1173-1179.
136.
Kulig M, Klettke U, Wahn V, et al: Development of seasonal allergic rhinitis during the first 7 years of life. J Allergy Clin Immunol 2000;106:832-839.
137.
Niederberger V, Niggemann B, Kraft D, Spitzauer S, Valenta R: Evolution of IgM, IgE and IgG(1-4) antibody responses in early childhood monitored with recombinant allergen components: implications for class switch mechanisms. Eur Immunol 2002;32:576-584.
138.
Lupinek C, Marth K, Niederberger V, Valenta R: Analysis of serum IgE reactivity profiles with microarrayed allergens indicates absence of de novo IgE sensitizations in adults. J Allergy Clin Immunol 2012;130:1418-1420.
139.
Hatzler L, Panetta V, Lau S, et al: Molecular spreading and predictive value of preclinical IgE response to Phleum pratense in children with hay fever. J Allergy Clin Immunol 2012;130:894-901.
140.
Bousquet J, Anto J, Auffray C, et al: MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine. Allergy 2011;66:596-604.
141.
Marth K, Novatchkova M, Focke-Tejkl M, et al: Tracing antigen signatures in the human IgE repertoire. Mol Immunol 2010;47:2323-2329.
142.
Collins AM, Thelian D, Basil M: Antigen valency as a determinant of the responsiveness of IgE-sensitized rat basophil leukemia cells. Int Arch Allergy Immunol 1995;107:547-556.
143.
Lund G, Willumsen N, Holm J, et al: Antibody repertoire complexity and effector cell biology determined by assays for IgE-mediated basophil and T-cell activation. J Immunol Methods 2012;383:4-20.
144.
Holm J, Willumsen N, Würtzen PA, Christensen LH, Lund K: Facilitated antigen presentation and its inhibition by blocking IgG antibodies depends on IgE repertoire complexity. J Allergy Clin Immunol 2011;127:1029-1037.
145.
Willumsen N, Holm J, Christensen LH, Würtzen PA, Lund K: The complexity of allergic patients' IgE repertoire correlates with serum concentration of allergen-specific IgE. Clin Exp Allergy 2012;42:1227-1236.
146.
Gieras A, Focke-Tejkl M, Ball T, et al: Molecular determinants of allergen-induced effector cell degranulation. J Allergy Clin Immunol 2007;119:384-390.
147.
van der Heijden FL, van Neerven RJ, van Katwijk M, Bos JD, Kapsenberg ML: Serum-IgE-facilitated allergen presentation in atopic disease. J Immunol 1993;150:3643-3650.
148.
Jiang N, He J, Weinstein JA, et al: Lineage structure of the human antibody repertoire in response to influenza vaccination. Sci Transl Med 2013;5:171ra19.
149.
Mersmann M, Meier D, Mersmann J, et al: Towards proteome scale antibody selections using phage display. N Biotechnol 2010;27:118-128.
150.
Turunen L, Takkinen K, Söderlund H, Pulli T: Automated panning and screening procedure on microplates for antibody generation from phage display libraries. J Biomol Screen 2009;14:282-293.
151.
Levin M, Davies AM, Liljekvist M, et al: Human IgE against the major allergen Bet v 1 - defining an epitope with limited cross-reactivity between different PR-10 family proteins. Clin Exp Allergy 2013, DOI: 10.1111/cea.12230.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.