{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T04:13:43Z","timestamp":1783224823690,"version":"3.54.6"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2009,6,1]],"date-time":"2009-06-01T00:00:00Z","timestamp":1243814400000},"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":[[2009,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Milk is one of the first components introduced into human diet. It also represents one of the first allergen sources, which induces IgE-mediated allergies in childhood ranging from gastrointestinal, skin, and respiratory manifestations to severe life-threatening manifestations, such as anaphylaxis. Here we isolated a cDNA coding for a major cow\u2019s milk allergen, \u03b1S1-casein, from a bovine mammary gland cDNA library with allergic patients\u2019 IgE Abs. Recombinant \u03b1S1-casein was expressed in Escherichia coli, purified, and characterized by circular dichroism as a folded protein. IgE epitopes of \u03b1S1-casein were determined with recombinant fragments and synthetic peptides spanning the \u03b1S1-casein sequence using microarrayed components and sera from 66 cow\u2019s milk-sensitized patients. The allergenic activity of r\u03b1S1-casein and the \u03b1S1-casein-derived peptides was determined using rat basophil leukemia cells transfected with human Fc\u03b5RI, which had been loaded with the patients\u2019 serum IgE. Our results demonstrate that r\u03b1S1-casein as well as \u03b1S1-casein-derived peptides exhibit IgE reactivity, but mainly the intact r\u03b1S1-casein induced strong basophil degranulation. These results suggest that primarily intact \u03b1S1-casein or larger IgE-reactive portions thereof are responsible for IgE-mediated symptoms of food allergy. Recombinant \u03b1S1-casein as well as \u03b1S1-casein-derived peptides may be used in clinical studies to further explore pathomechanisms of food allergy as well as for the development of new diagnostic and therapeutic strategies for milk allergy.<\/jats:p>","DOI":"10.4049\/jimmunol.0712366","type":"journal-article","created":{"date-parts":[[2009,5,19]],"date-time":"2009-05-19T17:00:29Z","timestamp":1242752429000},"page":"7019-7029","source":"Crossref","is-referenced-by-count":67,"title":["Cloning, Expression, and Mapping of Allergenic Determinants of \u03b1S1-Casein, a Major Cow\u2019s Milk Allergen"],"prefix":"10.1093","volume":"182","author":[{"given":"Ulrike","family":"Schulmeister","sequence":"first","affiliation":[{"name":"Institute of Medical and Chemical Laboratory Diagnostics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidrun","family":"Hochwallner","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Division of Immunopathology, Center for Physiology and Pathophysiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Swoboda","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Division of Immunopathology, Center for Physiology and Pathophysiology"},{"name":"Christian Doppler Laboratory for Allergy Research, Medical University of Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarete","family":"Focke-Tejkl","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Division of Immunopathology, Center for Physiology and Pathophysiology"},{"name":"Christian Doppler Laboratory for Allergy Research, Medical University of Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Geller","sequence":"additional","affiliation":[{"name":"Institute of Medical and Chemical Laboratory Diagnostics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mats","family":"Nystrand","sequence":"additional","affiliation":[{"name":"Phadia , Uppsala,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"H\u00e4rlin","sequence":"additional","affiliation":[{"name":"Phadia , Uppsala,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"Thalhamer","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Division of Allergy and Immunology, University of Salzburg ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Scheiblhofer","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Division of Allergy and Immunology, University of Salzburg ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Keller","sequence":"additional","affiliation":[{"name":"Institute for Chemistry, Structural Biology, Karl-Franzens-University , Graz,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bodo","family":"Niggemann","sequence":"additional","affiliation":[{"name":"Department of Pediatric Allergology and Pneumology, Hedwig-von-Rittberg-Zentrum, German Red Cross Hospital Westend , Berlin,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Quirce","sequence":"additional","affiliation":[{"name":"Hospital La Paz, Allergy Department , Madrid,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Ebner","sequence":"additional","affiliation":[{"name":"Allergy Clinic Reumannplatz , Vienna,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano","family":"Mari","sequence":"additional","affiliation":[{"name":"Division of Immunopathology, Department of Pathophysiology, Center for Clinical and Experimental Allergy, Istituto Dermopatico dell\u2019Immacolata-Istituto di Ricovero e Cura a Carattere Scientifico , Rome,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle","family":"Pauli","sequence":"additional","affiliation":[{"name":"Service de Pneumologie, H\u00f4pitaux Universitaires , Strasbourg,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udo","family":"Herz","sequence":"additional","affiliation":[{"name":"Mead Johnson Nutritionals , Evansville, IN 47712"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Valenta","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Division of Immunopathology, Center for Physiology and Pathophysiology"},{"name":"Christian Doppler Laboratory for Allergy Research, Medical University of Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Spitzauer","sequence":"additional","affiliation":[{"name":"Institute of Medical and Chemical Laboratory Diagnostics"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,6,1]]},"reference":[{"key":"2026012806300820700_R1","first-page":"1089","article-title":"Gastrointestinal food allergy: new insights into pathophysiology and clinical perspectives.","volume-title":"Gastroenterology","year":"2005"},{"key":"2026012806300820700_R2","first-page":"304","article-title":"Common manifestations of cow\u2019s milk allergy in children.","volume-title":"Lancet","year":"1978"},{"key":"2026012806300820700_R3","first-page":"1437","article-title":"Food allergy, II: Prevalence of organ manifestations of allergy-inducing food: a study on the basis of 173 cases, 1978\u20131982 (in German).","volume-title":"Schweiz Med. Wochenschr.","year":"1985"},{"key":"2026012806300820700_R4","first-page":"191","article-title":"Fatalities due to anaphylactic reactions to foods.","volume-title":"J. Allergy Clin. Immunol.","year":"2001"},{"key":"2026012806300820700_R5","first-page":"1173","article-title":"Natural course of sensitization to food and inhalant allergens during the first 6 years of life.","volume-title":"J. Allergy Clin. Immunol.","year":"1999"},{"key":"2026012806300820700_R6","first-page":"489","article-title":"Milk allergy: a survey of its incidence; experiments with a masked ingestion test.","volume-title":"J. Allergy","year":"1950"},{"key":"2026012806300820700_R7","first-page":"595","article-title":"Food allergy.","volume-title":"Mol. Nutr. Food Res.","year":"2006"},{"key":"2026012806300820700_R8","first-page":"470","article-title":"9. Food allergy.","volume-title":"J. Allergy Clin. Iimmunol.","year":"2006"},{"key":"2026012806300820700_R9","first-page":"64","article-title":"Kuhmilch als Ursache akuter Ern\u00e4hrungsst\u00f6rungen bei S\u00e4uglingen.","volume-title":"Monatschr. Kinderheilkunde","year":"1905"},{"key":"2026012806300820700_R10","first-page":"641","article-title":"Anaf. familiare per il latte di mucca: tentativie di terapia antianaf.","volume-title":"Pediatria","year":"1911"},{"key":"2026012806300820700_R11","first-page":"12","article-title":"Oral desensitization in children with milk and egg allergies obtains recovery in a significant proportion of cases: a randomized study in 60 children with cow\u2019s milk allergy and 90 children with egg allergy.","volume-title":"Eur. Ann. Allergy Clin. Immunol.","year":"2007"},{"key":"2026012806300820700_R12","first-page":"1679","article-title":"Allergen-responsive CD4+CD25+ regulatory T cells in children who have outgrown cow\u2019s milk allergy.","volume-title":"J. Exp. 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Allergy","year":"2005"},{"key":"2026012806300820700_R17","first-page":"1013","article-title":"Cow\u2019s milk allergens.","volume-title":"Allergy","year":"1998"},{"key":"2026012806300820700_R18","first-page":"306","article-title":"Allergenic epitopes of bovine \u03b1S1-casein recognized by human IgE and IgG.","volume-title":"Allergy","year":"1996"},{"key":"2026012806300820700_R19","first-page":"379","article-title":"Identification of IgE- and IgG-binding epitopes on \u03b1s1-casein: differences in patients with persistent and transient cow\u2019s milk allergy.","volume-title":"J. Allergy Clin. Immunol.","year":"2001"},{"key":"2026012806300820700_R20","first-page":"303","article-title":"Characterization of T cell epitopes in \u03b1s1-casein in cow\u2019s milk allergic, atopic and non-atopic children.","volume-title":"Clin. Exp. Allergy","year":"2006"},{"key":"2026012806300820700_R21","first-page":"119","article-title":"Role of human leucocyte antigen DQ in the presentation of T cell epitopes in the major cow\u2019s milk allergen \u03b1s1-casein.","volume-title":"Int. Arch. Allergy Immunol.","year":"2007"},{"key":"2026012806300820700_R22","first-page":"185","article-title":"Specific IgE levels in the diagnosis of immediate hypersensitivity to cows\u2019 milk protein in the infant.","volume-title":"J. Allergy Clin. Immunol.","year":"2001"},{"key":"2026012806300820700_R23","first-page":"680","article-title":"Cleavage of structural proteins during the assembly of the head of bacteriophage T4.","volume-title":"Nature","year":"1970"},{"key":"2026012806300820700_R24","first-page":"248","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.","volume-title":"Anal. Biochem.","year":"1976"},{"key":"2026012806300820700_R25","first-page":"2042","article-title":"Nonanaphylactic synthetic peptides derived from B cell epitopes of the major grass pollen allergen, Phl p 1, for allergy vaccination.","volume-title":"FASEB J.","year":"2001"},{"key":"2026012806300820700_R26","first-page":"836","article-title":"Induction of hepatitis A virus-neutralizing antibody by a virus-specific synthetic peptide.","volume-title":"J. Virol.","year":"1985"},{"key":"2026012806300820700_R27","first-page":"4350","article-title":"Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1979"},{"key":"2026012806300820700_R28"},{"key":"2026012806300820700_R29","first-page":"141","article-title":"Mediator release assays based on human and nurine immunoglobulin E in allergen standadization.","volume-title":"Clin. Exp. 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Immunol.","year":"2005"},{"key":"2026012806300820700_R34","first-page":"486","article-title":"Evaluation of the allergenicity and antigenicity of bovine-milk \u03b1s1-casein using extensively purified synthetic peptides.","volume-title":"Scand. J. Immunol.","year":"2004"},{"key":"2026012806300820700_R35","first-page":"1599","article-title":"Role of conformational and linear epitopes in the achievement of tolerance in cow\u2019s milk allergy.","volume-title":"Clin. Exp. Allergy","year":"2001"},{"key":"2026012806300820700_R36","first-page":"704","article-title":"IgE-binding peptides coupled to a commercial matrix as a diagnostic instrument for persistent cow\u2019s milk allergy.","volume-title":"J. Allergy Clin. Immunol.","year":"2005"},{"key":"2026012806300820700_R37","first-page":"384","article-title":"Molecular determinants of allergen-induced effector cell degranulation.","volume-title":"J. Allergy Clin. Immunol.","year":"2007"},{"key":"2026012806300820700_R38","first-page":"186","article-title":"Poor association between allergen-specific serum immunoglobulin E levels, skin sensitivity and basophil degranulation: a study with recombinant birch pollen allergen Bet v 1 and an immunoglobulin E detection system measuring immunoglobulin E capable of binding to Fc\u03b5RI.","volume-title":"Clin. Exp. Allergy","year":"2005"},{"key":"2026012806300820700_R39","first-page":"848","article-title":"Skin test results but not serology reflect immediate type respiratory sensitivity: a study performed with recombinant allergen molecules.","volume-title":"J. Invest. Dermatol.","year":"2001"},{"key":"2026012806300820700_R40","first-page":"268","article-title":"The predictive value of specific immunoglobulin E levels in serum for the outcome of oral food challenges.","volume-title":"Clin. Exp. Allergy","year":"2005"},{"key":"2026012806300820700_R41","first-page":"47","article-title":"Effect of T-cell peptides derived from Fel d 1 on allergic reactions and cytokine production in patients sensitive to cats: a randomised controlled trial.","volume-title":"Lancet","year":"2002"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/182\/11\/7019\/62682303\/9056.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/182\/11\/7019\/62682303\/9056.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T11:33:06Z","timestamp":1769599986000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/182\/11\/7019\/8006960"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,6,1]]},"references-count":41,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2009,6,1]]},"published-print":{"date-parts":[[2009,6,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.0712366","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2009,6]]},"published":{"date-parts":[[2009,6,1]]}}}