Allergenic activity of a major grass pollen allergen is elevated in the presence of nasal secretion

被引:28
作者
Bufe, A [1 ]
Gehlhar, K [1 ]
Schramm, G [1 ]
Schlaak, M [1 ]
Becker, WM [1 ]
机构
[1] Forschungszentrum Borstel, D-23845 Borstel, Germany
关键词
D O I
10.1164/ajrccm.157.4.9709040
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Phl p5 is a major allergen of timothy grass and causes rhinitis and bronchial asthma in nearly all patients allergic to grass pollen. The biochemical processing of this molecule by the nasal mucosa at its first encounter and possible changes of its biologic activity are unknown. Two isoforms of the allergen were expressed in Escherichia coli and subsequently purified. Conversion of these preparations to various forms with molecular size between 10 and 20 kD in the presence of nasal secretion was observed. Surprisingly, in skin prick test assays with allergic patients the mixture of converted peptides caused significantly higher allergic response when compared with the parent protein. Allergenic activity of the recombinant N-terminal Phl p5a and the C-terminal Phl p5b as measured by skin prick test and histamine release assays was significantly higher than that of the respective parent molecules. Using pancreatic rather than nasal secretion, Phl p5b was completely degraded and its allergenicity was almost completely reduced. Proteolytic degradation converts Phl p5 to defined fragments with increased allergenicity. Complete degradation of Phl p5 on the mucosa could be a preventive strategy to destroy its potency for the induction of an allergic response.
引用
收藏
页码:1269 / 1276
页数:8
相关论文
共 31 条
[21]   COMPARISON OF 4 GRASS-POLLEN SPECIES CONCERNING THEIR ALLERGENS OF GRASS GROUP-V BY 2D IMMUNOBLOTTING AND MICROSEQUENCING [J].
PETERSEN, A ;
SCHRAMM, G ;
BECKER, WM ;
SCHLAAK, M .
BIOLOGICAL CHEMISTRY HOPPE-SEYLER, 1993, 374 (09) :855-861
[22]   EPITOPE ANALYSIS OF ISOFORMS OF THE MAJOR ALLERGEN PHL-P-V BY FINGERPRINTING AND MICROSEQUENCING [J].
PETERSEN, A ;
BECKER, WM ;
SCHLAAK, M .
CLINICAL AND EXPERIMENTAL ALLERGY, 1994, 24 (03) :250-256
[23]   DNA SEQUENCING WITH CHAIN-TERMINATING INHIBITORS [J].
SANGER, F ;
NICKLEN, S ;
COULSON, AR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1977, 74 (12) :5463-5467
[24]   Mapping of IgE-binding epitopes on the recombinant major group I allergen of velvet grass pollen, rHol I 1 [J].
Schramm, G ;
Bufe, A ;
Petersen, A ;
Haas, H ;
Schlaak, M ;
Becker, WM .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1997, 99 (06) :781-787
[25]   Reduction in IgE binding to allergen variants generated by site-directed mutagenesis: Contribution of disulfide bonds to the antigenic structure of the major house dust mite allergen Der p 2 [J].
Smith, AM ;
Chapman, MD .
MOLECULAR IMMUNOLOGY, 1996, 33 (4-5) :399-405
[26]  
Stewart G A, 1993, Pediatr Allergy Immunol, V4, P163, DOI 10.1111/j.1399-3038.1993.tb00087.x
[27]   MECHANISM OF GRASS-POLLEN-INDUCED ASTHMA [J].
SUPHIOGLU, C ;
SINGH, MB ;
TAYLOR, P ;
BELLOMO, R ;
HOLMES, P ;
PUY, R ;
KNOX, RB .
LANCET, 1992, 339 (8793) :569-572
[28]   THE HUMAN IGE NETWORK [J].
SUTTON, BJ ;
GOULD, HJ .
NATURE, 1993, 366 (6454) :421-428
[29]   COMPARATIVE MODELING OF MAJOR HOUSE-DUST MITE ALLERGEN DER-P-I - STRUCTURE VALIDATION USING AN EXTENDED ENVIRONMENTAL AMINO-ACID PROPENSITY TABLE [J].
TOPHAM, CM ;
SRINIVASAN, N ;
THORPE, CJ ;
OVERINGTON, JP ;
KALSHEKER, NA .
PROTEIN ENGINEERING, 1994, 7 (07) :869-894
[30]   IGE EPITOPES ON THE CAT (FELIS-DOMESTICUS) MAJOR ALLERGEN FEL D-I - A STUDY WITH OVERLAPPING SYNTHETIC PEPTIDES [J].
VANMILLIGEN, FJ ;
VANTHOF, W ;
VANDENBERG, M ;
AALBERSE, RC .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1994, 93 (01) :34-43