NEW HORIZONS IN ALLERGY IMMUNOTHERAPY

ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY

Editorial Board:

NATHAN BACK, State University of New York at Buffalo

IRUN R. COHEN, The Weizmann Institute of Science

DAVID KRITCHEVSKY, Wistar Institute

ABEL LAJTHA, N. S. Kline Institute for Psychiatric Research

RODOLFO PAOLETTI, University of Milan

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NEW HORIZONS IN ALLERGY IMMUNOTHERAPY

Edited by

Alee Sehon University of Manitoba Winnipeg, Manitoba, Canada

Kent T. HayGlass University ofManitoba Winnipeg, Manitoba, Canada

and

Dietrieh Kraft Institute of General and Experimental Pathology Vienna, Austria

SPRINGER SCIENCE+BUSINESS MEDIA, LLC

Llbrary of Congress Cataloglng-ln-Publlcatlon Data

New horlzons In allergy iNmunotherapy / edlted by Alec Sehon. Kent T. HayGlass. and 01etrich Kraft.

p. c •. -- (Advances In experimental medlclne and blology ; v. 409)

"Proceedings of the 2nd International Conference on the Molecular Blology of Allergens and the AtopiC Im_une Response. held February 18-22. 1995. ln Quebec Clty. Canada"--T.p. verso.

Includes blbllographlcal references and index. ISBN 978-1-4613-7684-2 ISBN 978-1-4615-5855-2 (eBook) DOI 10.1007/978-1-4615-5855-2 1. Allergy--Immunotherapy--Congresses. 1. Sehon. Alec H.

II. HayGlass. Kent T. III. Kraft. Oietrlch. IV. International Conference on the Molecular Blology of Allergens and the Atoplc Immune Response (2nd : 1995 : Ouebec Clty. Ouebec) V. Serles.

[ONLM: 1. Hypersensltlvity. Immedlate--congresses. 2. Immunotherapy--congresses. 3. Allergens--genetics--congresses. 4. Recomblnant Protelns--lmmunology--congresses. Wl A0559 v.409 1996 / WO 300 N5317 19961 RC588.145N48 1996 616.97·06--dc21 ONLM/OLC for Library of Congress 96-50090

CIP

Proceedings ofthe Second International Conference on the Molecular Biology of Allergens and the Atopic Immune Response, held February 18-22, 1995, in Quebec City, Canada

ISBN 978-1-4613-7684-2

© 1996 Springer Science+Business Media New York Originally published by Plenum Press,New York in 1996 Softcover reprint of the hardcover 1 st edition 1996

109876543 2 1

AII rights reserved

No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher

FOREWORD

One of the main attractions of research into hypersensitivity disorders is that it brings together scientists from a very broad range of disciplines. As the most common hu­man immunologic disorder, it excites the interest and concern of clinicians, geneticists, basic and clinical immunologists, molecular biologists, biochemists, and physiologists. General agreement has been forged on the the pathophysiology of the disease and the mechanisms responsible for its maintenance, but many areas remain as black boxes for which we have only hypotheses.

In 1992 Vienna hosted an international symposium to consider the explosion of in­formation being generated by the identification, cloning, and expression of common envi­ronmental allergens: The present second international conference on the MOLECULAR BIOLOGY OF ALLERGENS AND THE ATOPIC IMMUNE RESPONSE, again jointly organized and co-chaired by Professors Alec Sehon (Winnipeg) and Dietrich Kraft (Vi­enna), provided an exciting opportunity for many leaders in this field to share data, argue hypotheses and seek future opportunities to enlarge our understanding of these very com­plex diseases. This symposium was co-sponsored by the International Union of Immu­nological Societies (I.U.I.S.) and the International Association of Allergology and Clinical Immunology. It was held in the hospitable and comfortably elegant surroundings of Que­bec City.

Over five days, data and opinions on many topical, often controversial, issues were presented which addressed (i) genetic factors predisposing, or perhaps protecting, any given individual from development of atopic disease; (ii) detailed molecular charac­terization of many of the major allergens known to be associated with atopic disease; (iii) examination of the characteristics of environmental antigens that lead to their (functional) definition as allergens in some individuals; (iv) mechanisms of allergic sensitization and the role played by different cell populations and cytokines in this process; and (v) novel approaches for therapy of atopic disease ranging from antigen-specific tolerization or pro­phylaxis to methods resulting in inhibition of IgE synthesis or function across the board, and a host of other topics critically reviewed in this volume.

Tremendous progress has been made in identifying, cloning, and expressing the ma­jor allergens responsible for atopic diseases. The implications that our increasing access to such well-defined materials has for diagnosis, experimental studies, and therapy of ongo­ing hypersensitivity disease were thoroughly explored. The field has clearly progressed from the cloning of a handful of the major allergens by pioneers in this area, beginning

• Molecular Biology and Immunology of Allergens. Eds. Dietrich Kraft and Alec Sehon, CRC Press, Inc., Boca Raton, Florida, 1993

v

vi Preface

only in 1988 with publication of the cDNA sequence of Der pi, to the current situation, where the widespread availability of a multitude of allergens allows us to pose questions about the physiological and practical relevance of different allergen isoforms. Clearly, with the current availability of these molecular tools, our ability to probe the induction, maintenance, expression, and suppression of allergic disease enters a new era.

The co-chairmen and the participants of this symposium express their gratitude for the generous support of the listed sponsors who made it possible to organize this confer­ence. Special thanks for the splendid organization and hospitality are expressed to Profes­sor Jacques Hebert (Quebec) and his colleague Dr. Yvan Boutin who were responsible for the splendid planning of the scientific program and the Symposium Secretariat.

Kent T. HayGlass, Ph.D. Winnipeg, Canada

ACKNOWLEDGMENTS

The financial assistance in support of this Symposium from the following agencies and companies is gratefully acknowledged.

Allergen Standardization Committee ALK Laboratories ASAHI Breweries Ltd. ClBA-GEIGY LTD. Connaught Laboratories Ltd. Medical Research Council of Canada Fujisawa Pharmaceutical Co., Ltd. Glaxo Canada Glaxo Nippon Ltd. Hoechst-Roussel Canada Inc. Hokuriku Seiyaku Co., Ltd. Immuno Aktiengesell Schaft ImmuLogic Pharmaceutical Corporation Kabi Pharmacia Kirin Brewery Co., Ltd. Kyorin Pharmaceutical Co., Ltd. Merck Frosst Canada Miles Inc., Pharmaceutical Division Nippon Boehringer Ingelheim Co., Ltd. Marion Merre! Dow, Inc. Nordic Merrel Dow Sandoz Canada Inc. Sanofi Diagnostics Pasteur, Inc. Schering Torii Pharmaceutical Co., Ltd. Wakamoto Pharmaceutical Co., Ltd.

(I.U.I.S.) (Denmark) (Japan) (Switzerland) (Canada)

(Japan) (Canada) (Japan) (Canada) (Japan) (Austria) (U.S.A.) (Sweden) (Japan) (Japan) (Canada) (U.S.A.) (Japan) (U.S.A.) (Canada) (Canada) (U.S.A.) (Canada) (Japan) (Japan)

vii

CONTENTS

1. Food Allergy in Atopic Dogs O. L. Frick

2. Mechanisms of Allergic Bronchoconstriction in the Rat . . . . . . . . . . . . . . . . . . . . 9 James G. Martin

3. The Role of Nebulized IFN-y in the Modulation of Allergic Responses Gideon Lack and Erwin W. Gelfand

4. Murine Animal Models to Study the Central Role ofT Cells in Immediate-Type

17

Hyersensitivity Responses ...................................... 25 Udo Herz, Uschi Lumpp, Angelika Daser, Erwin W. Gelfand, and

Harald Renz

5. Glutathione S-Transferase Induces Murine Dermatitis that Resembles Human Allergic Dermatitis ............................................ 33

Ching-Hsiang Hsu, Kaw-Yan Chua, Shau-Ku Huang, I-Ping Chiang, and Kue-Hsiung Hsieh

6. Effects ofrIL-12 Administration on an Antigen Specific Immune Response. . . . 39 Julia D. Rempel-Chin, Ming Dong Wang, and Kent T. HayGlass

7. Mapping the Genes for IgE Production and Allergy David G. Marsh

8. Genetic Factors in Asthma William Cookson

9. Regulation oflnterleukin-12 Signalling during T Helper Phenotype

43

55

Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 Nils G. Jacobson, Susanne 1. Szabo, Mebmet L. GuIer, James D. Gorham,

and Kenneth M. Murphy

10. Responsiveness to the Major Pollen Allergen of Parietaria officinalis Is Associated with Defined HLA-DRBI * Alleles in Italian and Spanish Allergic Patients .............................................. 75

Anna Ruffilli, Mauro D' Amato, Tonino Menna, Enrico Maggi, Guido Sacerdoti, and Carlos Lahoz

ix

x Contents

11. HLA-DR3 Is Associated with the IgE Immune Responsiveness to a Recombinant Allergen from Blomia tropicalis (BT) .................. 81

L. Caraballo, B. Martinez, S. Jimenez, and L. Puerta

12. Recombinant Allergens for Immunotherapy W. R. Thomas

13. Structural and Antigenic Studies of Cockroach Allergens and Their Relevance to

85

Asthma ..................................................... 95 Martin D. Chapman, Lisa D. Vailes, Mary Lou Hayden, David C. Benjamin,

Thomas A. E. Platts-Mills, and L. Karla Arruda

14. pJuFo: A Phagemid for Display of cDNA Libraries on Phage Surface Suitable for Selective Isolation of Clones Expressing Allergens ...... . . . . . . . . . . 103

Reto Crameri, Stefanie Hemmann, and Kurt Blaser

15. Automated Serology with Recombinant Allergens: A Feasibility Study. . . . . . . . III Reto Crameri, Jonas Lidholm, Gunter Menz, Hans Gronlund, and Kurt Blaser

16. Biological and Immunological Importance of Bet v 1 Isoforms .............. 117 M. Breitenbach, F. Ferreira, A. Jilek, I. Swoboda, C. Ebner,

K. Hoffmann-Sommergruber, P. Briza, o. Scheiner, and D. Kraft

17. Modulation ofIgE-Binding Properties of Tree Pollen Allergens by Site-Directed Mutagenesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 127

Fatima Ferreira, Angelika Rohlfs, Karin Hoffmann-Sommergruber, Siegfried Schenk, Christof Ebner, Peter Briza, Alexander Jilek, Dietrich Kraft, Michael Breitenbach, and Otto Scheiner

18. Advantages and Disadvantages of Recombinant Allergens and Peptides for Specific Immunotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137

Carsten Schou

19. T Cell Epitopes of Phi pi, Major Pollen Allergen of Timothy Grass (Phleum pratense): Crossreactivity with Group I Allergens of Different Grasses. . . 141

Siegfried Schenk, Heimo Breiteneder, Markus Susani, Nader Najafian, Sylvia Laffer, Michael Duchene, Rudolf Valenta, Gottfried Fischer, Otto Scheiner, Dietrich Kraft, and Christof Ebner

20. Recombinant Expression and Epitope Mapping of Grass Pollen Allergens 147 Cenk Suphioglu, Penelope M. Smith, Eng K. Ong, R. Bruce Knox, and

Mohan B. Singh

21. Molecular Characterization of Alternaria alternata and Cladosporium herbarum Allergens... . .. ... .. .. ..... . .. ... .... .. ... ... . . . .. . . . .. .. . .. . 157

Gernot Achatz, Hannes Oberkofler, Erich Lechenauer, Birgit Simon, Andrea Unger, Doris Kandler, Christoph Ebner, Hansjorg Prillinger, Dietrich Kraft, and Michael Breitenbach

22. Production of Recombinant Allergens and Their Application for Immunotherapy 163 Yasushi Okumura

Contents xi

23. Use of Recombinant Group 5 Allergens to Investigate IgE-Mediated Sensitization to Blomia tropicalis and Dermatophagoides pteronyssinus ................................................ 173

1. Karla Arruda, Lisa D. Vailes, Enrique Fernandez-Caldas, Charles K. Naspitz, Federico Montealegre, and Martin D. Chapman

24. Dual Effects of Allergen-mPEG Conjugates: Induction oflmmunological Suppression and Inactivation of Sensitized Mast Cells ................ 177

A. H. Sehon, S. Bitoh, and G. Lang

25. Recombinant Allergens: Steps on the Way to Diagnosis and Therapy of Type I Allergy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185

Rudolf Valenta, Sylvia Laffer, Susanne Vrtala, Hans Gronlund, Lena Elfman, Wolfgang R. Sperr, Peter Valent, Fatima Ferreira, Peter Mayer, Ekke Liehl, Susanne Heiss, Renate Steiner, Hans Georg Eichler, Markus Susani, and Dietrich Kraft

26. Production of a Recombinant Protein from Alternaria Containing the Reported N-Terminal of the Alt Al Allergen. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197

C. S. Barnes, F. Pacheco, J. Landuyt, D. Rosenthal, F. Hu, and J. Portnoy

27. Isolation of a cDNA Clone Encoding a Putative Alternaria alternata Alt a I Subunit ..................................................... 205

M. W. De Vouge, A. J. Thaker, 1. Zhang, I. H. A. Curran, G. Muradia, H. Rode, and H. M. Vijay

28. Peanut Hypersensitivity: IgE Binding Characteristics of a Recombinant Ara h I Protein ...................................................... 213

J. S. Stanley, R. M. Helm, G. Cockrell, A. W. Burks, and G. A. Bannon

29. Human T Cell Clones and Cell Lines Specific to Ovomucoid Recognize Different Domains and Consistently Express IL-5 . . . . . . . . . . . . . . . . . . .. 217

P. A. Eigenmann, S. K. Huang, D. G. Ho, and H. A. Sampson

30. Isolation and Cloning of Bet v I-Homologous Food Allergens from Celeriac (Apigl)andApple(Maldl) .................................... 219

K. Hoffmann-Sommergruber, M. Vanek-Krebitz, R. Ferris, G. O'Riordain, M. Susani, R. Hirschwehr, C. Ebner, H. Ahorn, D. Kraft, O. Scheiner, and H. Breiteneder

31. IgE and Monoclonal Antibody Reactivities to the Major Shrimp Allergen Pen a I (Tropomyosin) and Vertebrate Tropomyosins . . . . . . . . . . . . . . . . . . . . .. 225

Gerald Reese, Deborah Tracey, Carolyn B. Daul, and Samuel B. Lehrer

32. Immunomodulation with T Cell Reactive Peptides Barbara P. Wallner and Mohammad Luqman

33. Molecular Cloning and Immunological Characterization of the Group 7

231

Allergens of House Dust Mites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 241 H. D. Shen, K. Y Chua, K. H. Hsieh, and W. R. Thomas

xii Contents

34. Epitope Structure of Recombinant Isoallergens of Bet vI. . . . . . . . . . . . . . . . .. 243 J0rgen Nedergaard Larsen, Susanne Hauschildt Sparholt, and Henrik Ipsen

35. Characterisation of Recombinant Isoforms of Birch Pollen Allergen Bet vi .. " 251 M. D. Spangfort, H. Ipsen, S. H. Sparholt, S. Aasmul-Olsen, P. Osmark,

F. M. Poulsen, M. Larsen, E. M0rtz, P. Roepstorff, and 1. N. Larsen

36. Lol pH Allergen: Production and Characterization of the Recombinant Protein and Human Antibody Fragments ................................. 255

Alessandro Sidoli, Claudia De Lalla, Elena Tamborini, Anna Brandazza, and Paolo Arosio

37. Characterization of Group 1 Allergens from Eleven Grass Species ........... 261 S. Aasmul-Olsen, P. A. Wfutzen, M. Lombardero, H. L0wenstein, and

H. Ipsen

38. A Major Allergen Involved in IgE Mediated Cockroach Hypersensitivity Is a 90 kD Protein with Multiple IgE Binding Domains ..................... 267

Ricki M. Helm, Gael Cockrell, 1. Steve Stanley, Richard Brenner, A. Wesley Burks, and Gary A. Bannon

39. Molecular Characterization of Hor v 9: Conservation of a T-Cell Epitope among Group IX Pollen Allergens and Human VCAM and CD2 .............. 269

James D. Astwood and Robert D. Hill

40. Cytokine and Drug Modulation ofTNFa in Mast Cells .................... 279 Tong-Jun Lin, Antonio Enciso, Elyse Y. Bissonnette, Agnes Szczepek, and

A. Dean Befus

41. Synthesis and Storage of Regulatory Cytokines in Human Eosinophils . . . . . . .. 287 Redwan Moqbel

42. Allergen Dose Dependent Cytokine Production Regulates Specific IgE and IgG Antibody Production . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 295

Kurt Blaser

43. The Role of Accessory Cell Products in the Regulation ofT Cell Cytokine Production ................................................... 305

M. L. Kapsenberg, C. M. U. Hilkens, T. C. T. M. van der Pouw Kraan, E. A. Wierenga, and A. Snijders

44. In Vivo Direction ofCD4 T Cells to THI and TH2-Like Patterns ofCytokine Synthesis .................................................... 309

Kent T. HayGlass, Mingdong Wang, Randall S. Gieni, Cynthia Ellison, and John Gartner

45. Controversial Issues and Possible Answers on the Antigen-Specific Regulation of the IgE Antibody Response ................................... 317

Kimishige Ishizaka, Tatsumi Nakano, Yasuyuki Ishii, Yun-Cai Liu, Toshifumi Mikayama, and Akio Mori

Contents

46. In Situ Detection of Cytokines in Allergic Inflammation Q. A. Hamid and E. Minshall

47. Is Vaccination against IgE Possible? Lars Hellman

48. Role ofInterleukin-4 in the Development of Allergic Airway Inflammation and

xiii

327

337

Airway Hyperresponsiveness .................................... 343 M. Wills-Karp, S. H. Gavett, Brian Schofield, and F. Finkelman

49. The Roles ofCD40 and CD23 in IgE Regulation ......................... 349 Teruhito Yasui, Hiroshi Fujiwara, Masato Kamanaka, Tsutomu Kawabe,

Nobuaki Yoshida, Tadamitsu Kishimoto, and Hitoshi Kikutani

50. Absence of Mutations in the 6th Exon ofFceRI-~ ........................ 355 K. A. Deichmann, F. Hildebrandt, A. Heinzmann, S. Schlenther,1. Forster,

and 1. Kuehr

51. Role of Type 2 T Helper Cells (TH2) in Allergic Disorders ................. 359 P. Parronchi, S. Sampognaro, E. Maggi, and S. Romagnani

52. Diversity of Human T Cell Receptor Sequences ofT Cell Clones with Specificity for Bet v 1 Peptide/MHC II Complexes. . . . . . . . . . . . . . . . . .. 365

Heimo Breiteneder, Roswitha Hajek, Robert Huttinger, Christof Ebner, Siegfried Schenk, Dietrich Kraft, and Otto Scheiner

53. Identification of Differentially Expressed Genes in CD19+ve B Lymphocytes in Allergic Asthma .............................................. 375

Roslan B. Harun, Alexander F. Markham, and John F. 1. Morrison

54. Non Random Usage ofT Cell Receptor a Gene Expression in Atopy Using Anchored PCR ............................................... 381

A. H. Mansur, C. M. Gelder, D. Holland, D. A. Campell, A. Griffin, W. Cunliffe, A. F. Markham, and J. F. J. Morrison

55. Reduction ofIgE Antibody Binding to rDer p 2 Variants Generated by Site-Directed Mutagenesis ...................................... 391

Alisa M. Smith and Martin D. Chapman

56. Expression of the House Dust Mite Allergen Der p2 and Mutants in the Baker's Yeast Saccharomyces cerevisiae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 395

G. A. 1. Hakkaart, R. C. Aalberse, and R. van Ree

57. The Function of Allergens May Determine Allergenicity ................... 399 A. Bufe, G. Schramm, A. Petersen, M. Schlaak, and W. -M. Becker

58. Differential Gene Expression for Interleukin-13 and Other Cytokines in the Skin of Atopic Dermatitis Patients and Healthy Subjects. . . . . . . . . . . . . . . . . .. 403

I. Van der Ploeg, M. Tengvall Linder, 6. Hiigermark, C. -F. Wahlgren, and A. Scheynius

xiv Contents

59. Peptide Induced Anergy of Human Allergen-Specific T Cells ............... 405 Hans Y ssel, Stephan Fasler, Gregorio Aversa, and Jan E. de Vries

60. Natural and Recombinant Anti-IgE Autoantibodies. . . . . . . . . . . . . . . . . . . . . . . . 411 Beda M. Stadler, Martin Stampfli, Monique Vogel, Michael Rudolf,

Adrian ZUrcher, and Sylvia Miescher

61. Modulation of Anti-Allergen Immune Responses by Allergen-Antibody Complexes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 417

Jean-Marie R. Saint-Remy

62. Characterization of Allergenic Determinants on the C-Terminal Region of the r-Lol pl. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 425

P. Lamontagne, Y. , Boutin, C. Brunet, J. Boulanger, J. Berton, and J. Hebert

63. Anti-Idiotypic Antibodies in the Treatment of Allergies Jacques Hebert and Yvan Boutin

64. Enhanced Production and Gene Expression ofIl-5 in Bronchial Asthma: Possible Management of Atopic Diseases with IL-5 Specific Gene

431

Transcription Inhibitor ......................................... 439 Akio Mori, Matsunobu Suko, Osamu Kaminuma, Yoko Nishizaki,

Toshifumi Nagahori, Tadashi Mikami, Takeo Ohmura, Akihiko Hosino, Yumiko Asakura, and Hirokazu Okudaira

65. Peptide Mediated Regulation of Allergen Specific Immune Responses Jonathan R. Lamb and Robyn E. O'Hehir

66. Clinical Experience with Treatment of Allergies with T Cell Epitope Containing

451

Peptides .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 457 Philip S. Norman

67. Clinical Use of Recombinant Allergens and Epitopes ......... . . . . . . . . . . . . . 463 Jean Bousquet, Anne Des Roches, and Louis Paradis

68. Diagnostic and Therapeutic Use of Recombinant Allergens D. Kraft

Invited Contributors

471

475

Index... ... . ...... .. . .. .......... ............ ......... ... .. . ..... . .... 479