T Lymphocytes Structure, Functions, Choices NATO ASI Series Advanced Science Institutes Series A series presenting the results of activities sponsored by the NATO Science Committee, which aims at the dissemination of advanced scientific and technological knowledge, with a view to strengthening links between scientific communities. The series is published by an international board of publishers in conjunction with the NATO Scientific Affairs Division A Life Sciences Plenum Publishing Corporation B Physics New York and London C Mathematical and Physical Sciences Kluwer Academic Publishers D Behavioral and Social Sciences Dordrecht, Boston, and London E Applied Sciences F Computer and Systems Sciences Springer-Verlag G Ecological Sciences Berlin, Heidelberg, New York, London, H Cell Biology Paris, Tokyo, Hong Kong, and Barcelona 1 Global Environmental Change Recent Volumes in this Series Volume 227—Angiogenesis in Health and Disease edited by Michael E. 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Goffinet Series A: Life Sciences T Lymphocytes Structure, Functions, Choices Edited by Franco Celada The Hospital for Joint Diseases, New York University New York, New York and Benvenuto Pernis Columbia University New York, New York Springer Science+Business Media, LLC Proceedings of a NATO Advanced Study Institute on T Lymphocytes: Structure, Functions, Choices, held September 15-27, 1991, in Porto Conte (Alghero), Sardinia, Italy NATO-PCO-DATA BASE The electronic index to the NATO ASI Series provides full bibliographical references (with key words and/or abstracts) to more than 30,000 contributions from international scientists published in all sections of the NATO ASI Series. Access to the NATO-PCO-DATA BASE is possibel in two ways: -via online FILE 128 (NATO-PCO-DATA BASE) hosted by ESRIN, Via Galileo Galilei, I-00044 Frascati, Italy. Additional material to this book can be downloaded from http://extra.springer.com. Library of Congress Cata1og1ng-1n-PublIcatlon Data T Lymphocytes : structure, functions, choices / edited by Franco Celada and Benvenuto Pernls. p. cm. — (NATO ASI series. Series A, Life sciences ; vol. 233) "Proceedings of a NATO Advanceed Study Institute on T Lymphocytes: Structure, Functions, Choices, held September 15-27, 1991, in Porto Conte (Alghero), Sardinia, Italy."—T.p. verso. "Published 1n cooperation with NATO Scientific Affairs Division." Includes bibliographical references and index. ISBN 978-1-4613-6332-3 ISBN 978-1-4615-3054-1 (eBook) DOI 10.1007/978-1-4615-3054-1 1. T cells—Congresses. I. Celada, Franco. II. Pernls, Benvenuto. III. North Atlantic Treaty Organization. Scientific Affairs Division. IV. NATO Advanced Study Institute on T Lymphocytes: Structure, Functions, Choices (1991 : Porto Conte, Italy) V. Series: NATO ASI series. Series A, Life sciences ; v. 233. [DNLM: 1. T-Lymphocytes—physiology—congresses. WH200T1114 1991] QR185.8.T2T2 1992 599' .029—dc20 DNLM/DLC for Library of Congress 92-49284 CIP ISBN 978-1-4613-6332-3 © 1992 Springer Science+Business Media New York Originally published by Plenum Press in 1992 All 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 COMMITTEE Directors: Franco Celada and Benvenuto Pemis Secretary: Pierluigi Fiori Scientific Committee: K. Rajewsky, E. Sercarz, M. Siniscalco Faculty Members: O. Acuto, L. Adorini, J. Bodmer, W. Bodmer, C. Bona, H. Cantor, F. Celada, I. Cohen, K. Hannestad, E. Heber-Katz, K. Karjalainen, A. Lanzavecchia, F. Manca, D. Mathis, N. A. Mitchison, S. Nathenson, D. Parker, B. Pemis, E. Sercarz, A. Theofilopoulos, T. Tada, H. von Boehmer, M. Zanetti Local Staff: Paola Melis, Paola RappelJi v PREFACE This volume contains the proceedings of the NATO Advanced Study Institute held in Porto Conte (Alghero), Sardinia, September 15-27, 1991. The A.S.1. was attended by 86 graduate and postgraduate students from 18 different countries, and was hosted by the newly founded International Laboratory of Molecular Genetics of Porto Conte, directed by Prof. Marcello Siniscalco. The A.S.I. was funded by NATO Scientific Affairs Division, the International Union of Immunological Societies, the European Community (Directorate General for Science, Research and Development), the Italian Research Council, and the San Raffaele Institute of Milano. In addition, a number of students who reside in the U.S. received travel funds from the U.S. National Science Foundation, and the Turkish National Fund provided financial assistance to several students from Turkey. When we decided to organize a course on T lymphocytes, our concern was to reach a balance between the teaching of both the hard core principles and the latest experimental findings of cellular immunology, and the recently expanded interfaces with the not-yet known: hypotheses, speCUlations, new projections to be born from the discussions. A posteriori, we believe we have largely succeeded in this endeavor, or, to use a more objective statement, that the course turned out to be a balanced mixture of teaching and contributing, of learning and discussing as we had hoped, and that this happened by a number of mechanisms and factors for only a fraction of which we can claim responsibility or merit. Yes, we were responsible for the selection of the members of the scientific committee, and together with them for the choice of the faculty. Yes, we had the merit to select a venue which was ideal in terms of sheer beauty, but also relative isolation, and a relation (at least mental) to a new research institute in the labor of being born. Yes, the capable secretary of the course, who also brought an extraordinary local staff, was our choice. But what about the weather (twelve days without faltering, whose influence on everybody's mood was visible), the quality of the students and their willingness to ask, talk, engage? And what about the theorists of immunology, a small group of mathematicians and a physicist who came as observers, did not miss one session, and contributed constantly to the discussion? We hope that some of the flavor of these twelve days in Porto Conte will be preserved in this book. It contains 16 chapters written by faculty members and 8 by students who had contributed a presentation at the course. The basic theme of the course was the structure and the function of T lymphocytes. These cells are rightly considered to be the commanding elements of the immune system. In fact the immune response to protein antigens, those for which the distinction between self and non-self is most difficult and most important, is decided by T cells. For these antigens, B cells require the "help" or, more precisely, the "permission" ofT cells, and not the other vii way around. With this premise, it is not surprising that the structure and the function of T cells are particularly complex. To begin with, the T cell receptors do not recognize intact protein antigens but rather fragments of these, that have been broken down to the level of peptides in the antigen-presenting cells and are presented to the T cells after having been bound into a specific cleft of membrane molecules, the histocompatibility antigens. This process is grounded on clonal selection and is the basis of immunological tolerance. T cells are also involved in intercellular regulations that give to the immune system its capacity to respond in an integrated way with the maximum efficiency and an (inevitable) minimum of potentiality to inflict damage to the organism itself. Thus, the complexity of the immune system is to a large extent related to the complexity of the T- lymphocyte system, which is not likely to yield soon to a comprehensive analytical approach, including the exciting efforts of computerized simulations. The study of that system is, without doubt, at the cutting edge of our capacity to understand, and perhaps control, some major plagues that still affect the human species, like AIDS, and the major autoimmune diseases like multiple sclerosis, rheumatoid arthritis and juvenile diabetes. These underlying practical problems, as well as the intellectual challenge posed by the T system, explain the interest and excitement that was obvious in the faculty and students throughout the course. F. Celada B. Pemis viii CONTENTS 1. T-cell antigen and MHC recognition: Molecular analysis of human ()[/{3 TCR specific for a tetanus toxin-derived peptide ..................... . Brigitte Boilel, Myriam Ermonval, Ulrich Blank, and Oreste Acuto 2. Structure of the TCR-Ag-MHC complex ............................................... 17 Nadine Gervois, Bing-Yuan Wei, Paolo Dellabona, Jean Peccoud, Christophe Benoist, and Diane Mathis 3. Is recognition by the T cell receptor highly constrained or very degenerate?........................................................................ 25 Navreet K. Nanda and Eli E. Sercarz 4. Characteristics of foreign and self peptides endogenously bound to MHC class I molecules ........................................................... 37 Grada M. van Bleek and Stanley G. Nathenson 5. Positive and negative selection of T cells ................................................ 45 Harald von Boehmer 6. Peripheral tolerance ......................................................................... 61 David C. Parker 7. The functional relationship between preferential use of newly synthesized class II molecules and their stable association with peptides ........................................................................ 71 Colin Watts and Antonio Lanzavecchia 8. Epitope selection and autoimmunity........................................ ............. 75 N. Avrion Mitchison 9. HLA-A2 allorecognition and subtyped diversification............................... 89 A. Raul Castaflo Garcia and Jose A. Lopez de Castro 10. On the antigenicity of antibody idiotypes ............................................... 97 Kristian Hannestad 11. Idiotype interactions between T cells ................................................... 105 Benvenuto Pernis ix 12. A network of self interactions........................................................... 111 Maurizio Zanetti 13. Stimulation of lymphocytes by anti-idiotypes bearing the internal image of viral antigens .......................................................... 121 Habib Zaghouani and Constantin Bona 14. Cloned suppressor T cells --their identity, functions and mediators ........... 135 Tomio Tada, Tadahiro Inoue, Shuichi Kubo, and Yoshihiro Asano 15. The autoreactive T cell receptor: Structure and biological activity ............. 145 Ellen Heber-Katz 16. The relationship between diabetes and lymphopenia in the BB rat............. 153 Sarah Joseph, Geoffrey Butcher, William Smith, and Joyce Baird 17. RT6, an unusually polymorphic T cell specific membrane protein linked to type I autoimmune diabetes in rats and mice ................. 163 Friedrich Haag, Friedrich Koch-Nolte, Christiane Hollman, and Heinz Ganter Thiele 18. Alternative pathways of signal transduction after ligation of the TCR by bacterial superantigen ............................................... 169 Hsi Liu and Harvey Cantor 19. Molecular analysis of the interactions between staphylococcal enterotoxin A superantigen and the human MIlC class II molecules................................................................. 179 N. Labrecque, J. Thibodeau, A. Herman, H. McGrath, P. Marrack, J. Kappler, and R.-P. Sekaly 20. Immunosuppression by MHC class II blockade..................................... 187 Luciano Adorini 21. Recognition of HIV antigens by human T helper cells ............................. 195 Fabrizio Manca, Giuseppina Li Pira, Silvia Ratto, and Eleonora Molinari 22. Proliferative responses to the V3 region of HIV envelope are enhanced following immunization with V3:Ty virus-like particles in mice .................................................................. 207 Stephen J. Harris, Andrew J.H. Gearing, Guy T. Layton, Sally E. Adams, Susan M. Kingsman, and Alan J. Kingsman 23. Teaching immunology: a Montessori approach using a computer model of the immune system .................................................. 215 Franco Celada and Philip E. Seiden 24. Modelling T cell memory in vivo and in vitro ........................................ 227 Angela R. McLean x 25. Oligoclonal T cells expressing the TeR V{36 gene product following IL-2 culture of ovarian carcinoma-derived lymphocytes................ 235 2va Halapi, Mahmood Jeddi-Tehrapi, Johan Grunewald, Roland Andersson, Christina Hising, Giuseppe Masucci, Hakan Mellstedt, and Rolf Kiessling 26. Comparisons of the V- delta-! expressing T cells in synovial fluid and peripheral blood of patients with chronic arthritis ................. 241 Kalle Soderstrom, Anders Bueht, Thomas Hultman, Mathias Uhlen, Ethel Nilsson, Alvar Gronberg, Satish Jindal, and Rolf Kiessling 27. Bispecific monoclonal antibody-targeted cytotoxic T lymphocytes can recycle........................................................................ 247 J.A.C. Voorthuis, E. Braakman, C.P.M. Ronteltap, N.E.B.A.M. van Eseh, and R.L.H. Bolhuis Index ................................................................................................. 251 xi