Visualization of clustered IgE epitopes on α-lactalbumin

被引:49
作者
Hochwallner, Heidrun [2 ]
Schulmeister, Ulrike [2 ]
Swoboda, Ines [1 ]
Focke-Tejkl, Margit [1 ]
Civaj, Vera [1 ]
Balic, Nadja [2 ]
Nystrand, Mats [3 ]
Harlin, Annika [3 ]
Thalhamer, Josef [4 ]
Scheiblhofer, Sandra [4 ]
Keller, Walter [5 ]
Paykov, Tea [5 ]
Zafred, Domen [5 ]
Niggemann, Bodo [6 ]
Quirce, Santiago [7 ]
Mari, Adriano [8 ]
Pauli, Gabrielle [9 ]
Ebner, Christof [10 ]
Papadopoulos, Nikolaos G. [11 ]
Herz, Udo [12 ]
van Tol, Eric A. F. [12 ]
Valenta, Rudolf [1 ]
Spitzauer, Susanne [2 ]
机构
[1] Med Univ Vienna, Christian Doppler Lab Allergy Res, Div Immunopathol, Dept Pathophysiol,Ctr Pathophysiol Infect & Immun, A-1090 Vienna, Austria
[2] Med Univ Vienna, Dept Med & Chem Lab Diagnost, A-1090 Vienna, Austria
[3] Phadia AB, Uppsala, Sweden
[4] Salzburg Univ, Christian Doppler Lab Allergy Diag & Therapy, Dept Mol Biol, A-5020 Salzburg, Austria
[5] Graz Univ, Inst Mol Biosci, A-8010 Graz, Austria
[6] German Red Cross Hosp, Berlin, Germany
[7] Hosp La Paz, Dept Allergy, Madrid, Spain
[8] IRCCS, IDI, Ctr Clin & Expt Allergol, Rome, Italy
[9] Hop Univ, Serv Pneumol, Strasbourg, France
[10] Allergy Clin Reumannpl, Vienna, Austria
[11] Univ Athens, Dept Allergy, Pediat Clin 2, GR-10679 Athens, Greece
[12] Mead Johnson Nutr, Evansville, IN USA
基金
奥地利科学基金会;
关键词
Allergen; food allergy; milk allergy; recombinant allergen; IgE epitope; GRASS-POLLEN ALLERGEN; IMMUNOGLOBULIN-E LEVELS; COWS MILK ALLERGY; BOVINE BETA-LACTOGLOBULIN; CROSS-REACTIVITY; SYNTHETIC PEPTIDES; BINDING; PROTEIN; DETERMINANTS; EXPRESSION;
D O I
10.1016/j.jaci.2010.03.007
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: alpha-Lactalbumin (alpha-La) is a major cow's milk (CM) allergen responsible for allergic reactions in infants. Objective: We performed molecular, structural, and immunologic characterization of alpha-La. Methods: Recombinant alpha-lactalbumin (r alpha-La) was expressed in Escherichia coli, purified to homogeneity, and characterized by means of mass spectrometry and circular dichroism, and its allergenic activity was studied by using microarray technology, as well as in a basophil histamine release assay. IgE epitope mapping was performed with synthetic peptides. Results: According to circular dichroism analysis, rot-La represented a folded protein with a high thermal stability and refolding capacity. r alpha-La reacted with IgE antibodies from 57.6% of patients with CM allergy (n = 66) and induced the strongest basophil degranulation with sera from patients with CM allergy who had exhibited gastrointestinal symptoms or severe systemic reactions on CM exposure. r alpha-La contained sequential and conformational IgE epitopes. Superposition of IgE-reactive peptides onto the 3-dimensional structure of alpha-La revealed a close vicinity of the N- and C-terminal peptides within a surface-exposed patch. Conclusions: r alpha-La can be used for the diagnosis of patients with severe allergic reactions to CM and serves as a paradigmatic tool for the development of therapeutic strategies for CM allergy. (J Allergy Clin Immunol 2010;125:1279-85.)
引用
收藏
页码:1279 / 1285
页数:7
相关论文
共 50 条
[1]   HUMAN IGE-BINDING SYNTHETIC PEPTIDES OF BOVINE BETA-LACTOGLOBULIN AND ALPHA-LACTALBUMIN - INVITRO CROSS-REACTIVITY OF THE ALLERGENS [J].
ADAMS, SL ;
BARNETT, D ;
WALSH, BJ ;
PEARCE, RJ ;
HILL, DJ ;
HOWDEN, MEH .
IMMUNOLOGY AND CELL BIOLOGY, 1991, 69 :191-197
[2]   THE CCP4 SUITE - PROGRAMS FOR PROTEIN CRYSTALLOGRAPHY [J].
BAILEY, S .
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1994, 50 :760-763
[3]  
BALDO BA, 1984, AUST J DAIRY TECHNOL, V39, P120
[4]  
BALL T, 1994, J BIOL CHEM, V269, P28323
[5]   IgE cross-reactivity with caseins from different species in humans allergic to cow's milk [J].
Bernard, H ;
Creminon, C ;
Negroni, L ;
Peltre, G ;
Wal, JM .
FOOD AND AGRICULTURAL IMMUNOLOGY, 1999, 11 (01) :101-111
[6]   The predictive value of specific immunoglobulin E levels in serum for the outcome of oral food challenges [J].
Celik-Bilgili, S ;
Mehl, A ;
Verstege, A ;
Staden, U ;
Nocon, M ;
Beyer, K ;
Niggemann, B .
CLINICAL AND EXPERIMENTAL ALLERGY, 2005, 35 (03) :268-273
[7]   Crystal structures of apo- and holo-bovine α-lactalbumin at 2.2-A resolution reveal an effect of calcium on inter-lobe interactions [J].
Chrysina, ED ;
Brew, K ;
Acharya, KR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (47) :37021-37029
[8]   Nutritional and functional characteristics of whey proteins in food products [J].
de Wit, JN .
JOURNAL OF DAIRY SCIENCE, 1998, 81 (03) :597-608
[9]  
Docena GH, 1996, ALLERGY, V51, P412, DOI 10.1111/j.1398-9995.1996.tb00151.x
[10]   A Combination Vaccine for Allergy and Rhinovirus Infections Based on Rhinovirus-Derived Surface Protein VP1 and a Nonallergenic Peptide of the Major Timothy Grass Pollen Allergen Phl p 1 [J].
Edlmayr, Johanna ;
Niespodziana, Katarzyna ;
Linhart, Birgit ;
Focke-Tejkl, Margarete ;
Westritschnig, Kerstin ;
Scheiblhofer, Sandra ;
Stoecklinger, Angelika ;
Kneidinger, Michael ;
Valent, Peter ;
Campana, Raffaela ;
Thalhamer, Josef ;
Popow-Kraupp, Theresia ;
Valenta, Rudolf .
JOURNAL OF IMMUNOLOGY, 2009, 182 (10) :6298-6306