{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T12:59:11Z","timestamp":1777294751120,"version":"3.51.4"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2013,7,1]],"date-time":"2013-07-01T00:00:00Z","timestamp":1372636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Detailed understanding of how Abs of the IgE isotype interact with allergen at the onset of an allergic reaction is of great importance for deciphering mechanisms involved in the development of disease and may aid in the design of hypoallergenic variants. In this study, we have used a set of human monoclonal IgE Abs derived from the repertoires of allergic individuals, specific for the major timothy grass pollen allergen Phl p 1, to gain detailed information on the interaction between Abs and allergen. These allergen-specific IgE are to varying degrees cross-reactive toward both different allergen isoforms and various group 1 allergens originating from other grass species. The usage of human monoclonal IgE, as an alternative to polyclonal preparations or mouse Abs, allowed us to locate several important IgE-binding epitopes on the C-terminal domain of Phl p 1, all clustered to an IgE-binding \u201chot spot.\u201d By introducing three mutations in the IgE-binding area of the C-terminal domain we were able to significantly reduce its reactivity with serum IgE. In conclusion, our study shows the great potential of using human monoclonal IgE as a tool for studies of the molecular interactions taking place during allergic responses. Furthermore, we present a novel IgE-hyporeactive fragment with the potential to be used as a safer hypoallergenic alternative in specific immunotherapy than the pollen extracts used today.<\/jats:p>","DOI":"10.4049\/jimmunol.1202051","type":"journal-article","created":{"date-parts":[[2013,6,13]],"date-time":"2013-06-13T04:06:15Z","timestamp":1371096375000},"page":"551-560","source":"Crossref","is-referenced-by-count":17,"title":["Phl p 1\u2013Specific Human Monoclonal IgE and Design of a Hypoallergenic Group 1 Grass Pollen Allergen Fragment"],"prefix":"10.1093","volume":"191","author":[{"given":"Mattias","family":"Levin","sequence":"first","affiliation":[{"name":"Department of Immunotechnology, Lund University , S-223 81 Lund,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frida","family":"Rydnert","sequence":"additional","affiliation":[{"name":"Department of Immunotechnology, Lund University , S-223 81 Lund,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"K\u00e4llstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Sk\u00e5ne University Hospital , SE-205 02 Malm\u00f6,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lor Wai","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Surgery-Otorhinolaryngology, Head and Neck Surgery, University of Adelaide , Adelaide 5000, South Australia,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter J","family":"Wormald","sequence":"additional","affiliation":[{"name":"Department of Surgery-Otorhinolaryngology, Head and Neck Surgery, University of Adelaide , Adelaide 5000, South Australia,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malin","family":"Lindstedt","sequence":"additional","affiliation":[{"name":"Department of Immunotechnology, Lund University , S-223 81 Lund,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lennart","family":"Greiff","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Sk\u00e5ne University Hospital , SE-211 85 Lund,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mats","family":"Ohlin","sequence":"additional","affiliation":[{"name":"Department of Immunotechnology, Lund University , S-223 81 Lund,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,7,15]]},"reference":[{"key":"2025032405094227100_r1","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.jaci.2007.05.025","article-title":"Advances in asthma, allergy mechanisms, and genetics in 2006","volume":"120","author":"Finkelman","year":"2007","journal-title":"J. Allergy Clin. Immunol."},{"key":"2025032405094227100_r2","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1146\/annurev.immunol.21.120601.141103","article-title":"The biology of IGE and the basis of allergic disease","volume":"21","author":"Gould","year":"2003","journal-title":"Annu. Rev. Immunol."},{"key":"2025032405094227100_r3","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/nri2273","article-title":"IgE in allergy and asthma today","volume":"8","author":"Gould","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"2025032405094227100_r4","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1159\/000069013","article-title":"Characteristics and immunobiology of grass pollen allergens","volume":"130","author":"Andersson","year":"2003","journal-title":"Int. Arch. Allergy Immunol."},{"key":"2025032405094227100_r5","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1111\/j.1651-2227.2010.02028.x","article-title":"Swedish translation and validation of the Pediatric Allergic Disease Quality of Life Questionnaire (PADQLQ)","volume":"100","author":"Kiotseridis","year":"2011","journal-title":"Acta Paediatr."},{"key":"2025032405094227100_r6","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1111\/j.1398-9995.2009.02269.x","article-title":"Allergic rhinitis and the common cold: high cost to society","volume":"65","author":"Hellgren","year":"2010","journal-title":"Allergy"},{"key":"2025032405094227100_r7","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1056\/NEJM199908123410702","article-title":"Long-term clinical efficacy of grass-pollen immunotherapy","volume":"341","author":"Durham","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"2025032405094227100_r8","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1016\/S0140-6736(00)78276-6","article-title":"Prophylactic inoculation against hay fever","volume":"177","author":"Noon","year":"1911","journal-title":"Lancet"},{"key":"2025032405094227100_r9","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1111\/j.1365-2222.2009.03443.x","article-title":"Developments in allergen-specific immunotherapy: from allergen extracts to allergy vaccines bypassing allergen-specific immunoglobulin E and T cell reactivity","volume":"40","author":"Focke","year":"2010","journal-title":"Clin. Exp. Allergy"},{"key":"2025032405094227100_r10","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1046\/j.1365-2222.2000.00910.x","article-title":"Safety of allergen-specific immunotherapy. Relation between dosage regimen, allergen extract, disease and systemic side-effects during induction treatment","volume":"30","author":"Mellerup","year":"2000","journal-title":"Clin. Exp. Allergy"},{"key":"2025032405094227100_r11","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.jaci.2011.02.016","article-title":"Recombinant allergens: what does the future hold?","volume":"127","author":"Valenta","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"2025032405094227100_r12","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0065-2776(04)82003-0","article-title":"Immunotherapy of allergic disease","volume":"82","author":"Valenta","year":"2004","journal-title":"Adv. Immunol."},{"key":"2025032405094227100_r13","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/S0091-6749(03)02022-0","article-title":"Inhibition of allergen-IgE binding to B cells by IgG antibodies after grass pollen immunotherapy","volume":"112","author":"Wachholz","year":"2003","journal-title":"J. Allergy Clin. Immunol."},{"key":"2025032405094227100_r14","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1046\/j.1365-2222.2003.01699.x","article-title":"Allergen-specific immunotherapy with a monophosphoryl lipid A-adjuvanted vaccine: reduced seasonally boosted immunoglobulin E production and inhibition of basophil histamine release by therapy-induced blocking antibodies","volume":"33","author":"Mothes","year":"2003","journal-title":"Clin. Exp. Allergy"},{"key":"2025032405094227100_r15","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.coi.2006.09.013","article-title":"Immunoregulation by targeting T cells in the treatment of allergy and asthma","volume":"18","author":"Larch\u00e9","year":"2006","journal-title":"Curr. Opin. Immunol."},{"key":"2025032405094227100_r16","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/0091-6749(94)90075-2","article-title":"IgE-binding capacity of recombinant timothy grass (Phleum pratense) pollen allergens","volume":"94","author":"Laffer","year":"1994","journal-title":"J. Allergy Clin. Immunol."},{"key":"2025032405094227100_r17","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1159\/000110887","article-title":"Antigenic similarity among group 1 allergens from grasses and quantitation ELISA using monoclonal antibodies to Phl p 1","volume":"145","author":"Duffort","year":"2008","journal-title":"Int. Arch. Allergy Immunol."},{"key":"2025032405094227100_r18","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1016\/j.jaci.2006.02.012","article-title":"Spatial clustering of the IgE epitopes on the major timothy grass pollen allergen Phl p 1: importance for allergenic activity","volume":"117","author":"Flicker","year":"2006","journal-title":"J. Allergy Clin. Immunol."},{"key":"2025032405094227100_r19","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/0161-5890(95)00152-2","article-title":"Common IgE-epitopes of recombinant Phl p I, the major timothy grass pollen allergen and natural group I grass pollen isoallergens","volume":"33","author":"Laffer","year":"1996","journal-title":"Mol. Immunol."},{"key":"2025032405094227100_r20","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1111\/j.1432-1033.1997.00886.x","article-title":"Biochemical and immunological characterization of recombinant allergen Lol p 1","volume":"249","author":"Tamborini","year":"1997","journal-title":"Eur. J. Biochem."},{"key":"2025032405094227100_r21","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1159\/000236709","article-title":"Isolation and characterization of group-I isoallergens from Bermuda grass pollen","volume":"104","author":"Smith","year":"1994","journal-title":"Int. Arch. Allergy Immunol."},{"key":"2025032405094227100_r22","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.jmb.2006.06.062","article-title":"The human IgE-encoding transcriptome to assess antibody repertoires and repertoire evolution","volume":"362","author":"Andr\u00e9asson","year":"2006","journal-title":"J. Mol. Biol."},{"key":"2025032405094227100_r23","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.1016\/j.molimm.2008.01.004","article-title":"A common idiotype in IgE and its relation to recognition of the grass pollen allergen Phl p 2","volume":"45","author":"Persson","year":"2008","journal-title":"Mol. Immunol."},{"key":"2025032405094227100_r24","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1093\/protein\/gzn024","article-title":"In vitro evolution of an antibody fragment population to find high-affinity hapten binders","volume":"21","author":"Persson","year":"2008","journal-title":"Protein Eng. Des. Sel."},{"key":"2025032405094227100_r25","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.jaci.2008.05.026","article-title":"Several distinct properties of the IgE repertoire determine effector cell degranulation in response to allergen challenge","volume":"122","author":"Christensen","year":"2008","journal-title":"J. Allergy Clin. Immunol."},{"key":"2025032405094227100_r26","doi-asserted-by":"crossref","first-page":"4966","DOI":"10.4049\/jimmunol.0904038","article-title":"Isoallergen variations contribute to the overall complexity of effector cell degranulation: effect mediated through differentiated IgE affinity","volume":"184","author":"Christensen","year":"2010","journal-title":"J. Immunol."},{"key":"2025032405094227100_r27","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/j.jaci.2011.01.062","article-title":"Facilitated antigen presentation and its inhibition by blocking IgG antibodies depends on IgE repertoire complexity","volume":"127","author":"Holm","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"2025032405094227100_r28","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1016\/j.jaci.2007.06.041","article-title":"Delineating the specificity of an IgE-encoding transcriptome","volume":"120","author":"Persson","year":"2007","journal-title":"J. Allergy Clin. Immunol."},{"key":"2025032405094227100_r29","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1111\/j.1365-2222.2011.03724.x","article-title":"Diversity of immunoglobulin E-encoding transcripts in sinus mucosa of subjects diagnosed with non-allergic fungal eosinophilic sinusitis","volume":"41","author":"Levin","year":"2011","journal-title":"Clin. Exp. Allergy"},{"key":"2025032405094227100_r30","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1472-6750-9-14","article-title":"A multi-Fc-species system for recombinant antibody production","volume":"9","author":"Moutel","year":"2009","journal-title":"BMC Biotechnol."},{"key":"2025032405094227100_r31","doi-asserted-by":"crossref","first-page":"W503","DOI":"10.1093\/nar\/gkn316","article-title":"IMGT\/V-QUEST: the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysis","volume":"36","author":"Brochet","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"2025032405094227100_r32","first-page":"132","article-title":"The IMGT unique numbering for Immunoglobulins, T cell receptors and Ig-like domains","volume":"7","author":"Lefranc","year":"1997","journal-title":"The Immunologist"},{"key":"2025032405094227100_r33","doi-asserted-by":"crossref","first-page":"6986","DOI":"10.4049\/jimmunol.1000445","article-title":"Individual variation in the germline Ig gene repertoire inferred from variable region gene rearrangements","volume":"184","author":"Boyd","year":"2010","journal-title":"J. Immunol."},{"key":"2025032405094227100_r34","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S1074-7613(00)00006-6","article-title":"Diversity in the CDR3 region of VH is sufficient for most antibody specificities","volume":"13","author":"Xu","year":"2000","journal-title":"Immunity"},{"key":"2025032405094227100_r35","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.4049\/jimmunol.0902942","article-title":"IgE transcripts in the circulation of allergic children reflect a classical antigen-driven B cell response and not a superantigen-like activation","volume":"185","author":"Kerzel","year":"2010","journal-title":"J. Immunol."},{"key":"2025032405094227100_r36","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1007\/s11882-009-0055-9","article-title":"Allergen databases: current status and perspectives","volume":"9","author":"Mari","year":"2009","journal-title":"Curr. Allergy Asthma Rep."},{"key":"2025032405094227100_r37","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1002\/1521-4141(200208)32:8<2156::AID-IMMU2156>3.0.CO;2-A","article-title":"Conversion of grass pollen allergen-specific human IgE into a protective IgG1 antibody","volume":"32","author":"Flicker","year":"2002","journal-title":"Eur. J. Immunol."},{"key":"2025032405094227100_r38","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1159\/000236850","article-title":"Rabbit IgG directed to a synthetic C-terminal peptide of the major grass pollen allergen Lol p I inhibits human basophil histamine release induced by natural Lol p I","volume":"106","author":"van Ree","year":"1995","journal-title":"Int. Arch. Allergy Immunol."},{"key":"2025032405094227100_r39","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1096\/fasebj.13.11.1277","article-title":"B cell epitopes of the major timothy grass pollen allergen, Phl p 1, revealed by gene fragmentation as candidates for immunotherapy","volume":"13","author":"Ball","year":"1999","journal-title":"FASEB J."},{"key":"2025032405094227100_r40","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1096\/fj.01-0016fje","article-title":"Nonanaphylactic synthetic peptides derived from B cell epitopes of the major grass pollen allergen, Phl p 1, for allergy vaccination","volume":"15","author":"Focke","year":"2001","journal-title":"FASEB J."},{"key":"2025032405094227100_r41","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1111\/j.1398-9995.2008.01910.x","article-title":"Reducing allergenicity by altering allergen fold: a mosaic protein of Phl p 1 for allergy vaccination","volume":"64","author":"Ball","year":"2009","journal-title":"Allergy"},{"key":"2025032405094227100_r42","doi-asserted-by":"crossref","first-page":"943","DOI":"10.4049\/jimmunol.1000405","article-title":"Molecular determinants of T cell epitope recognition to the common timothy grass allergen","volume":"185","author":"Oseroff","year":"2010","journal-title":"J. Immunol."},{"key":"2025032405094227100_r43","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.vaccine.2007.10.048","article-title":"Humoral immunity targeting site I of antigenic domain 2 of glycoprotein B upon immunization with different cytomegalovirus candidate vaccines","volume":"26","author":"Axelsson","year":"2007","journal-title":"Vaccine"},{"key":"2025032405094227100_r44","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1128\/cdli.2.3.325-329.1995","article-title":"Human antibody reactivity against the lower matrix protein (pp65) produced by cytomegalovirus","volume":"2","author":"Ohlin","year":"1995","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"2025032405094227100_r45","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1128\/CVI.00561-10","article-title":"Antibodies recognizing protective pertussis toxin epitopes are preferentially elicited by natural infection versus acellular immunization","volume":"18","author":"Sutherland","year":"2011","journal-title":"Clin. Vaccine Immunol."},{"key":"2025032405094227100_r46","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1128\/CVI.00418-10","article-title":"Antibody recognition of porcine circovirus type 2 capsid protein epitopes after vaccination, infection, and disease","volume":"18","author":"Trible","year":"2011","journal-title":"Clin. Vaccine Immunol."},{"key":"2025032405094227100_r47","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1128\/JVI.00866-09","article-title":"Differential specificity and immunogenicity of adenovirus type 5 neutralizing antibodies elicited by natural infection or immunization","volume":"84","author":"Cheng","year":"2010","journal-title":"J. Virol."},{"key":"2025032405094227100_r48","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1046\/j.1365-2567.1997.00268.x","article-title":"Antigen dose-dependent predominance of either direct or sequential switch in IgE antibody responses","volume":"91","author":"Sudowe","year":"1997","journal-title":"Immunology"},{"key":"2025032405094227100_r49","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/j.1365-2222.1995.tb01036.x","article-title":"Differences between specificities of IgE and IgG4 antibodies: studies using recombinant chain 1 and chain 2 of the major cat allergen Felis domesticus (Fel d) I","volume":"25","author":"Van Milligen","year":"1995","journal-title":"Clin. Exp. Allergy"},{"key":"2025032405094227100_r50","doi-asserted-by":"crossref","first-page":"10967","DOI":"10.1074\/jbc.271.18.10967","article-title":"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","volume":"271","author":"Steinberger","year":"1996","journal-title":"J. Biol. Chem."},{"key":"2025032405094227100_r51","doi-asserted-by":"crossref","first-page":"e27780","DOI":"10.1371\/journal.pone.0027780","article-title":"Human anti-V3 HIV-1 monoclonal antibodies encoded by the VH5-51\/VL lambda genes define a conserved antigenic structure","volume":"6","author":"Gorny","year":"2011","journal-title":"PLoS ONE"},{"key":"2025032405094227100_r52","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/nature11371","article-title":"Structural and genetic basis for development of broadly neutralizing influenza antibodies","volume":"489","author":"Lingwood","year":"2012","journal-title":"Nature"},{"key":"2025032405094227100_r53","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1111\/j.1365-2222.2009.03380.x","article-title":"Molecular variability of group 1 and 5 grass pollen allergens between Pooideae species: implications for immunotherapy","volume":"40","author":"Chabre","year":"2010","journal-title":"Clin. Exp. Allergy"},{"key":"2025032405094227100_r54","doi-asserted-by":"crossref","first-page":"4014","DOI":"10.1021\/pr900359p","article-title":"Mass spectrometric investigation of molecular variability of grass pollen group 1 allergens","volume":"8","author":"Fenaille","year":"2009","journal-title":"J. Proteome Res."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/191\/2\/551\/62510193\/1202051.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/191\/2\/551\/62510193\/1202051.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T22:56:58Z","timestamp":1742857018000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/191\/2\/551\/7991191"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,7]]},"references-count":54,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2013,7,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1202051","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2013,7]]},"published":{"date-parts":[[2013,7]]}}}