Immune Regulation Experimental Biology and Medicine Immune Regulation, Edited by Marc Feldmann and N

Immune Regulation Experimental Biology and Medicine Immune Regulation, edited by Marc Feldmann and N. A. Mitchison, 1985 Human T Cell Clones: A New Approach to Immune Regu• lation, edited by Marc Feldmann, Jonathan R. Lamb, and James N. Woody, 1985 Growth, Cancer, and the Cell Cycle, edited by Philip Skehan and Susan J. Friedman, 1984 Ir Genes: Past, Present, and Future, edited by Carl W. Pierce, Susan E. Cullen, Judith A. Kapp, Benjamin D. Schwartz, and Donald C. Shreffler, 1983 Methods in Protein Sequence Analysis. edited by Marshall Elzinga, 1982 Inflammatory Diseases and Copper, edited by John R. J. Sorenson, 1982 Membrane Fluidity: Biophysical Techniques and Cellular Regulation, edited by Morris Kates and Amis Kuksis, 1980 IMMUNE REGULATION

Edited by

Marc Feldmann and N. A. Mitchison

Humana Press . Clifton, New Jersey Library of Congress Cataloging in Publication Data Main entry under title: Immune regulation. (Experimental biology and medicine) Based on papers presented at a conference held in 1984 at Cambridge. England. Includes index. . I. Immune response-Regulation-Congresses. 1. Feldmann , Marc. II. Mitchison, N. Avrion. III. Series: Experimental biology and medici ne (Clifton, N.J .) [DNLM: I. Cell Differentiation• congresses. 2. Immunity, Cellular-<:ongresses. 3. L ymphocytes-<:ytology-<:ongresses. 4. Lymphocytes• immunology-<:ongresses. QW 568 1315 1984] QR186.1437 1985 616.07'9 85-5786 1SBN-\3: 978-1-4612-9390-3 e-1SBN-\3 : 978-1-4612-4996-2 DOl: 10.1007/978-1-4612-4996-2 ©1985 The Humana Press Inc. So/trover reprint of the hardcover I st edition 1985 Crescent Manor PO Box 2148 Cli fton, NJ 07015

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. PREFACE

Leukocyte culture conferences have a long pedigree. This volume records some of the scientific highlights of the 16th such annual con• ference, and is a witness to the continuing evolution and popularity of leukocyte culture and of immunology. There is strong evidence of the widening horizons of immunology, both technically, with the obviously major impact of molecular biology into our understanding of cellular processes, and also conceptually. Traditionally, the 'proceedings' of these conferences have been published. But have the books produced really recorded the major part of the conference, the informal, friendly, but intense and some• times heated exchanges that take place between workers in tackling very similar problems and systems and which are at the heart of every successful conference? Unfortunately this essence cannot be incorpo• rated by soliciting manuscripts. For this reason, we have changed the format of publication, retaining published versions of the symposium papers, but requesting the workshop chairmen to produce a summary of the major new observations and areas of controversy highlighted in their sessions, as a vehicle for defining current areas of interest and debate. Not an easy task, as the workshop topics were culled from the abstracts submitted by the participants, rather than being on predefined topics. The unseasonal warmth in Cambridge was reflected in the atmos• phere of the conference, the organization of which benefited from the administrative skills of Jean Bacon, Philippa Wells, Mr. Peter Irving, and Mrs. Jennifer Hodd (Conference Contact, Cambridge), scientific advice from: Dr. B. Askonas, Dr. P. C. L. Beverley, Dr. M. Crumpton, Dr. M. Feldmann, Dr. M. Greaves, Dr. J. Ivanyi, Dr. J. Kay, Prof. P. Lachmann, Prof. N. A. Mitchison, Dr. M. Owen, Dr. E. Simpson, Dr. R. Taylor, and Dr. T. T wose. Financial support, without which this meeting would simply not have been possible, came from: British Society of Immunology, Can• cer Research Campaign, Celltech Ltd., DNAX Research Institute, Ge• netic Systems Corporation, Glaxo pic, ICI Pharmaceuticals pic, Impe• rial Cancer Research Fund, Leukaemia Research Fund, National Institutes of Health, The Wellcome Trust, Behring Diagnostics Ltd,

v vi Preface

Elsevier Publications, Laboratory Impex Ltd, Mercia Brocades Ltd, Nyegaard Ltd, Sera Lab Ltd, Serotec Ltd, and Seward Laboratory. We are grateful to the above for their contributions to this confer• ence, but in the last resort, the quality of a conference depends on the participants, and their enthusiasm was much appreciated.

Marc Feldmann N. A. Mitchison CONTENTS

Preface...... v List of Participants ...... xi

I. T CELL RECEPTORS Molecular and Functional Analysis of the Human T Cell Antigen/MHC Receptor ...... 3 Oreste Acuto, Marina Fabbi, and Ellis L. Reinherz Expression Patterns of the Beta Chain of the T Cell Receptor for Antigen ...... 15 Stephen M. Hedrick and Mark M. Davis Non Antigen-Specific Surface Molecules Involved in T Lymphocyte Function ...... 27 J.-c. Cerottini, H. R. MacDonald, J. Lowenthal, and R. Shimonkevitz T Cell Activation Antigens: Kinetics, Tissue Distribution, Molecular Weights, and Functions; Induction on Non T Cell Lines by Lymphokines ...... 39 D. Olive, P. Dubreuil, D. Charmot, C. Mawas, and P. Mannoni The Induction of Antigen Specific Unresponsiveness in Cloned T Lymphocytes ...... 51 J. R. Lamb and E. D. Zanders

WORKSHOP SUMMARIES Signals in B Cell Activation ...... 61 A. Schimpl and R. B. Corley Molecular Events in T Lymphocyte Activation ...... 65 J. Gordin Kaplan and John E. Kay Human Regulatory Cell Interactions ...... 71 Nancy Hogg and J. Farrant Human Natural Killer Cells ...... 75 Rolf Kiessling and Hugh Pross Control of MHC Gene Expression ...... 79 J. G. Frelinger and M. J. Owen

vii viii Contents

II. GROWTH AND DIFFERENTIATION FACTORS Haemopoietic Cell Growth Factor: Characterisation and Mode of Action ...... 83 A. D. Whetton and T. M. Dexter Regulation of Human B Lymphocytes Differentiation: Characteristics of B Cell Stimulatory Factors ...... 89 T. Hirano, H. Kikutani, K. Shimizu, H. Kishi, T. Taga, K. Ishibashi, S. Inui, S. Kashiwamura, N. Nakano, Y. Miki, T. Nakagawa, and T. Kishimoto The Human B Cell Cycle: Activation, Proliferation, and Differentiation ...... 101 Julian L. Ambrus, Jr. and Anthony S. Fauci Possible Autoregulatory Roles of Interleukin 1 for Normal Human Epithelial Cells, Monocytes, and B Lymphocytes ...... 111 J. J. Oppenheim, K. Matsushima, K. Onozaki, A. Procopio, and G. Scala Cloning of an IgE Immunoregulatory Factor by Expression in Mammalian Cells ...... 121 C. Martens, T. Huff, P. Jardieu, K. Ishizaka, and K. Moore

WORKSHOP SUMMARIES Normal and Abnormal B Cell Regulation ...... 131 David W. Scott and Klaus Eichmann Probing the T-Cell Repertoire ...... 135 A. Moretta and C. J. M. Melief Role of Thymus T Cell Differentiation ...... 141 J. J. T. Owen and R. Scollay Regulation of NK Activity ...... 145 John Ortaldo and Graham Flannery Receptors Involved in T Cell Activation ...... 151 Dominique J. Charron and Michael J. Crumpton

III. LYMPHOCYTE TRANSFORMATION Transformation of Cells by Epstein-Barr Virus: An Hypothesis ...... 159 Beverly E. Griffin Human T-Cell Lymphotropic Retroviruses (HTLV) Associated with T-Cell Malignancy and Immunodeficiency: In Vitro Studies ...... 167 Mikulas Popovic and Robert C. Gallo Contents ix

Stage Specific Transforming Genes in Lymphoid Neoplasms ...... 181 M. A. Lane, H. A. F. Stephens, M. B. Tobin, and Kevin Doherty Molecular Cloning and Expression of cDNAs Encoding the Human Interleukin-2 Receptor ...... 185 Warren J. Leonard, Joel M. Depper, Gerald R. Crabtree, Stuart Rudikoff, Janet Pumphrey, Richard J. Robb, Martin Kronke, Penny B. Svetlik, Nancy J. Peffer, Thomas A. Waldman, and Warner C. Greene Mantle Zone and Germinal Center B Cells Respond to Different Activation Signals ...... 197 Jeffrey A. Ledbetter, Paul J. Martin, and Edward A. Clark Development of T Cells Within the Thymus ...... 207 J. J. T. Owen and E. J. Jenkinson

IV. SELECTIVE RECOGNITION BY T AND 8 CELLS lntrathymic Differentiation and the T Cell Repertoire ...... 215 Roland Scollay Molecular Nature of T Cell Recognition of Antigen ...... 225 Emil R. Unanue, Paul M. Allen, and Evelyn A. Kurt-Jones Recognition of Viral Nucleoprotein by Influenza A Specific Cytotoxic T Cells ...... 231 A. R. M. Townsend, A. J. McMichael, and G. G. Brownlee The Chemistry of Antigen-Antibody Union ...... 243 Elizabeth D. Getzoff, John A. Tainer, and Richard A. Lerner Peptides as Potential Vaccines Against Foot and Mouth Disease ...... 259 F. Brown

WORKSHOP SUMMARIES Bone Marrow Differentiation ...... 267 J. G. Sharp and Ellen E. E. Jarrett Role of Cell Surface Molecules in T Cell Triggering ...... 273 P. C. L. Beverley and J. P. Revillard Mechanisms of T Cell Suppression ...... 279 G. L. Asherson and E. Culbert x Contents

Mechanisms of Immunological Perturbations...... 287 Susanna Cunningham-Rundies and Richard L. O'Brien Regulation of T Cell Growth...... 293 Amnon Altman and Vladimir A. Nesmeyanov v. ACCESSORY CELLS AND ANTIGEN PRESENTATION Inducer Accessory Cells as Regulators of the Immune Response...... • ...... 303 David R. Katz Functional Aspects of Accessory Cell Heterogeneity ...... 311 P. Erb, G. Ramila, I. Sklenar, and M. Kennedy Can Epithelial Cells Present Surface Autoantigens? ...... 323 Ian Todd, Marco Londei, Ricardo Pujol-Borrell, Marc Feldmann, and G. Franco Bottazzo Antigen Processing: A Reevaluation ...... 335 Jan Klein, Peter Walden, and Zoltan A. Nagy The Nature and Functions of Follicular Dendritic Cells ...... 345 G. G. B. Klaus and J. H. Humphrey

WORKSHOP SUMMARIES Mechanisms of Autoimmunity ...... 357 R. B. Taylor and A. Basten Function of Effector T Cells ...... 363 Ben Bonavida and Elizabeth Simpson Antigen Presenting Cells ...... " 369 Jay A. Berzofsky and Kozo Yokomuro Progress in Antimicrobial Immunity ...... 375 Juraj Ivanyi and Fernando Plata Molecular Mediators of Lymphocyte Activation and Proliferation .•...... 379 R. Callard and B. M. Vose Index ...... 385 PARTICIPANTS

ORESTE ACUTO . Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts PAUL M. ALLEN . Harvard Medical School, Boston, Massachusetts AMNON ALTMAN . Scripps Clinic, La Jolla, California JULIAN L. AMBRUS, JR. . National Institutes of Health, Bethesda, Maryland G. L. ASHERSON Clinical Research Center, Harrow, UK A. BASTEN . University of Sydney, Sydney, Australia JAY A. BERZOFSKY National Cancer Institute, Bethesda, Maryland P. C. L. BEVERLY University College Hospital School of Medicine, London, UK BEN BONAVIDA . UCLA School of Medicine, Los Angeles, California G. FRANCO BOTTAZZO . Middlesex Hospital Medical School, London, UK F. BROWN Wellcome Biotechnology, Surrey, UK G. G. BROWNLEY . John Radcliffe Hospital, Oxford , UK R. CALLARD . Institute of Child Health, London, UK J. -c. CEROTTINI LudWig Institute for Cancer Research, Lausanne, Switzerland D. CHARMOT . Centre d'Immunologie, Marseille, France DOMINIQUE J. CHARRON . Lab d'Immunologie, Marseille, France EDWARD A. CLARK . Genetic Systems Corporation, Seattle, Washington R. B. CORLEY Duke Medical Center, Durham, North Carolina GERALD R. CRABTREE National Cancer Institute, Bethesda, Maryland MICHAEL J. CRUMPTON Imperial Cancer Research Fund, London, UK E. CULBERT . ICI, Cheshire, UK SUSANNA CUNNINGHAM-RUNDLES . Sloan-Kettering Cancer Cen• ter, New York, New York MARK M. DAVIS . Stanford University, Stanford, California JOEL M. DEPPER . National Cancer Institute, Bethesda, Maryland T. M. DEXTER Paterson Laboratories, Manchester, UK

xi xii Participants

KEVIN DOHERTY Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts P. DUBREUIL . Centre d'Immunologie, Marseille, France KLAUS EICHMANN . Max-Planck Institute fUr Biologie, Freiburg, Fed• eral Republic of Germany P. ERB . Institute fUr Mikrobiologie and Hygiene, Basel, Switzerland MARINA FABBI . Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts J. FARRANT . Clinical Research Center, Harrow, UK ANTHONY S. FAUCI . National Institute of Allergy and Infectious Dis- eases, Bethesda, Maryland MARC FELDMANN . Middlesex Hospital Medical School, London, UK GRAHAM FLANNERY . La Trobe University, Victoria, Australia J. G. FRELINGER . University of North Carolina, Chapel Hill, North Carolina ROBERT C. GALLO . National Cancer Institute, Bethesda, Maryland ELIZABETH D. GETZOFF . Research Institute of Scripps Clinic, La Jolla, California WARNER C. GREENE . National Cancer Institute, Bethesda, Maryland BEVERLY E. GRIFFIN . Imperial Cancer Research Fund, London, UK STEPHEN M. HEDRICK . University of California, San Diego, California T. HIRANO . Osaka University, Osaka, Japan NANCY HOGG . Imperial Cancer Research Fund, London, UK T. HUFF . Johns Hopkins University, Good Samaritan Hospital, Baltimore, Maryland J. H. HUMPHREY . Royal Postgraduate Medical School, London, UK S. INUI . Osaka University, Osaka, Japan K. ISHIBASHI . Osaka University, Osaka, Japan K. ISHIZAKA . Johns Hopkins University, Good Samaritan Hospital, Baltimore, Maryland JURAJ IVANYI . Wellcome Research Laboratories, Kent, UK P. JARDIEU . Johns Hopkins University, Good Samaritan Hospital, Baltimore, Maryland ELLEN E. E. JARRETT . University of Glasgow, Glasgow, UK E. J. JENKINSON . University of Birmingham, Birmingham, UK J. GORDIN KAPLAN . The University of Alberta, Edmonton, Canada S. KASHIWAMURA . Osaka University, Osaka, Japan DAVID R. KATZ . Middlesex Hospital School, London, UK JOHN E. KAY . University of Sussex, Brighton, UK Participants xiii

M. KENNEDY University of Basel, Basel, Switzerland ROLF KIESSLING Karolinska Institute, Stockholm, Sweden H. KIKUT ANI . Osaka University, Osaka, Japan T. KISHIMOTO Osaka University, Osaka, Japan G. G. B. KLAUS . National Institute for Medical Research, London, UK H. KISHI . Osaka University, Osaka, Japa!1 JAN KLEIN . Max-Planck Institut fUr Biologie, TUbingen, Federal Repub• lic of Germany MARTIN KRONKE . National Cancer Institute, Bethesda, Maryland EVELYN A. KURT-JONES . Harvard Medical School, Boston, Massa- chusetts J. R. LAMB . University College London, London, UK M. -A. LANE Dana-Farber Cancer Institute, Boston, Massachusetts JEFFREY A. LEDBETTER Genetic Systems, Seattle, Washington WARREN J. LEONARD National Institutes of Health, Bethesda, Maryland RICHARD A. LERNER . Research Institute of Scripps Clinic, La Jolla, California MARCO LON DEI The Middlesex Hospital Medical School, London, UK J. LOWENTHAL Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland H. R. MACDONALD . Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland P. MANNONI . University of Alberta, Edmonton, Canada PAUL J. MARTIN . Genetic Systems Corporation, Seattle, Washington C. MARTENS . DNA X Research Institute, Palo Alto, California K. MA TSUSHIMA . Institute of Biological Chemistry, 2nd University Medical School, Napoli, Italy C. MAWAS . Centre d'immunologie, Marseille, France A. J. MCMICHAEL . John Radcliffe Hospital, Oxford, UK C. J. M. MELIEF . Cent. Laboratory of Netherlands Red Cross, Amsterdam, Netherlands Y. MIKI . Osaka University, Osaka, Japan K. MOORE . DNA X Research Institute of Molecular and Cellular Biology, Palo Alto, California ALESSANDRO MORETTA . LudWig Institute for Cancer Research, Lausanne, Switzerland ZOLTAN A. NAGY . Max-Planck Institut fUr Biologie, TUbingen, Federal Republic of Germany xiv Participants

T. NAKAGAWA . Osaka University, Osaka, Japan N. NAKANO . Osaka University, Osaka, Japan VLADIMIR A. NESMEYANOV . Shemyakin Institute Bioorganic Chem- istry, Moscow, USSR RICHARD L. O'BRIEN . Creighton University, Omaha, Nebraska D. OLIVE . Centre d'immunologie, Marseille, France K. ON OZAKI . Institute of Biological Chemistry, 2nd University Medical School, Napoli, Italy J. J. OPPENHEIM . National Cancer Institute, Frederick, Maryland JOHN ORTALDO . National Cancer Institute, Frederick, Maryland J. J. T. OWEN University of Birmingham Medical School, Birmingham, UK M. J. OWEN University College London, London, UK NANCY J. PEFFER National Cancer Institute, Bethesda, Maryland FERNANDO PLATA . Institut Pasteur, Paris, France MIKULAS POPOVIC . National Institutes of Health, Bethesda, Maryland A. PROCOPIO . Institute for Biological Chemistry, 2nd University Med- ical School, Napoli, Italy HUGH PROSS . Ontario Cancer Foundation, Ontario, Canada RICARDO PUJOL-BORRELL . University College London, London, UK JANET PUMPHREY . National Cancer Institute, Bethesda, Maryland G. RAMILA . University of Basel, Basel, Switzerland ELLIS L. REINHERZ . Dana-Farber Cancer Institute, Boston, Massachusetts J. P. REVILLARD H6pital E. Herriot, Lyon, France RICHARD J. ROBB E. I. du Pont de Nemours & Co., Glenolden, Pennsylvania STUART RUDIKOFF National Cancer Institute, Bethesda, Maryland G. SCALA . Institute of Biological Chemistry, 2nd University Medical School. Napoli, Italy A. SCHIMPL . Institute fUr Virology u. Immunbiologie WUrzburg, Federal R~public of Germany ROLAND SCOLLAY . Walter and Eliza Hall Institute, VictOria, Australia DAVID W. SCOTT . University of Rochester, Rochester, New York J. G. SHARP . University of Nebraska Medical Center, Omaha, Nebraska K. SHIMIZU . Osaka Univeristy, Osaka, Japan R. SHIMONKEVITZ . Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland ELIZABETH SIMPSON . Clinical Research Centre, Middlesex, UK Participants xv

I. SKLENAR Institute for Microbiology, University of Basel, Basel, Switzerland H. A. F. STEPHENS Dana-Farber Cancer Institute and Harvard Med- ical School, Boston, Massachusetts PENNY B. SVETLIK . National Cancer Institute, Bethesda, Maryland T. TAGA . Osaka University, Osaka, Japan JOHN A. T AINER . Scripps Clinic, La Jolla, California R. B. TAYLOR University of Bristol, Bristol, UK M. B. TOBIN Dana-Farber Cancer Institute, Boston, Massachusetts IAN TODD University College London, London, UK A. R. M. TOWNSEND . John Radcliffe Hospital, Oxford, UK EMIL R. UNANUE Harvard Medical School, Boston, Massachusetts B. M. VOSE . ICI Pharmaceutical, Cheshire, UK PETER WALDEN . Max-Planck Institut fUr Biologie, TUbingen, Federal Republic of Germany THOMAS A. WALDMANN . National Cancer Institute, Bethesda, Maryland A. D. WHETTON Paterson Laboratories, Christie Hospital & Radium Institute, Manchester, UK KOZO YOKOMURA . Nippon Medical School, Tokyo, Japan E. D. ZANDERS University College London, London, UK