Receptors, antibodies and disease Ciba Foundation symposium 90 1982 Pitman London Receptors, antibodies and disease The Ciba Foundation is an international scientific and educational charity. It was established in 1947 by the Swiss chemical and pharmaceutical company of CIBA Limited-now CIBA-GEIGY Limited. The Foundation operates independently in London under English trust law. The Ciba Foundation exists to promote international cooperation in medical and chemical research. It organizes international multidisciplinary meetings on topics that seem ready for discussion by a small group of research workers. The papers and discussions are published in the Ciba Foundation series. The Foundation organizes many other meetings, maintains a library which is open to all graduates in science or medicine who are visiting or working in London, and provides an information service for scientists. The Ciba Foundation also functions as a centre where scientists from any part of the world may stay during working visits to London. Receptors, antibodies and disease Ciba Foundation symposium 90 1982 Pitman London 0C iba Foundation 1982 ISBN 0 272 79654 9 Published in August 1982 by Pitman Ltd, London. Distributed in North America by CIBA Pharmaceutical Company (Medical Education Administration), Summit, NJ 07006, USA Suggested series entry for library catalogues: Ciba Foundation symposia Ciba Foundation symposium 90 x + 312 pages, 49 figures, 35 tables Evered, David Receptors, antibodies and disease.-(Ciba foundation symposium; 90) 1. Immune response4ongresses 2. Immunoglobins-Congresses I. Title 11. Whelan, Julie 111. Series 616.07'95 OR186 Text set in 10/12 pt Linotron 202 Times, printed and bound in Great Britain at The Pitman Press, Bath Contents Symposium on Receptors, antibodies and disease, held at the Ciba Foundation, London, 27-29 October 1981 Editors: David Evered (Organizer) and Julie Whelan N. A. MITCHISON (Chairman) Introduction 1 M. RODBELL Structure-function relationships in adenylate cyclase systems 3 Discussion 11 I. M. ROITT and L. C. DE CARVALHO The immunological basis of autoimmune disease 22 Discussion 30 J. G. KNIGHT and D. D. ADAMS The genetic basis of autoimmune disease 35 Discussion 52 N. A. MITCHISON T cell recognition and interaction in the immune system 57 Discussion 69 S. JACOBS and P. CUATRECASAS Insulin receptors and insulin recep- tor antibodies: structure-function relationships 82 Discussion 89 C. R. KAHN, M. KASUGA, G. L. KING and C. GRUNFELD Autoantibodies to insulin receptors in man: immunological deter- minants and mechanisms of action 91 Discussion 105 V vi CONTENTS B. REES SMITH and P. R. BUCKLAND Structure-function relations of the thyrotropin receptor 114 Discussion 125 R. HALL, S. McLACHLAN, A. M. McGREGOR, A. P. WEETMAN and B . REES SMITH Thyrotropin receptor antibodies: clinico-pathological correlations 133 Discussion 144 G. F. BOITTAZZO, H. A. DREXHAGE and E. L. KHOURY Thyroid antibodies in thyroid diseases 153 Discussion 167 J. M. LINDSTROM Structure of the acetylcholine receptor and specifici- ties of antibodies to it in myasthenia gravis 178 Discussion 191 A. G. ENGEL and G. FUMAGALLI Mechanisms of acetylcholine recep- tor loss from the neuromuscular junction 197 Discussion 219 J. NEWSOM-DAVIS, A. VINCENT and N. WILLCOX Acetylcholine receptor antibody: clinical and experimental aspects 225 Discussion 230 L. C. HARRISON, J. CALLAGHAN, J. C. VENTER, C. M. FRASERand M. L. KALINER Atopy, autonomic function and @-adrenergicr eceptor autoantibodies 248 Discussion 255 H. G. FRIESEN, R. P. C. SHIU, H. ELSHOLTZ, S. SIMPSON and J. HUGHES Prolactin and growth hormone receptors 263 Discussion 274 M. BLECHER Speculations on potential anti-receptor autoimmune diseases 279 Discussion 293 Index of contributors 301 Subject index 303 Participants L. BITENSKY Division of Cellular Biology, The Mathilda and Terence Kennedy Institute of Rheumatology, 6 Bute Gardens, London W6 7DW, UK M. BLECHER Department of Biochemistry, Georgetown University School of Medicine, Washington, DC 20007, USA G. F. BOTTAZZO Department of Immunology, Arthur Stanley House, Middlesex Hospital Medical School, 40-50 Tottenham Street, London W1P 9PG, UK M. J. CRUMPTON Imperial Cancer Research Fund Laboratories, PO Box 123, Lincoln’s Inn Fields, London WC2A 3PX, UK T. F. DAVIES Thyroid Section, Division of Endocrinology, The Mount Sinai Medical Center, One Gustave L. Levy Place, New York, New York 10029, USA D. B. DRACHMAN Neuromuscular Unit, Johns Hopkins University School of Medicine, c/o 317 Traylor Bldg., Baltimore, Maryland 21205, USA A. G. ENGEL Department of Neurology, Mayo Clinic, Rochester, Minn- esota 55901, USA H. G. FRIESEN Department of Physiology, University of Manitoba Facul- ty of Medicine, 770 Bannatyne Avenue, Winnipeg, Canada R3E OW3 S. FUCHS Department of Chemical Immunology, The Weizmann Institute of Science, Rehovot, Israel R. HALL Department of Medicine, Welsh National School of Medicine, Heath Park, Cardiff CF4 4XN, UK L. C. HARRISON Endocrine Laboratory, Department of Diabetes and Endocrinology, c/o Post Office, The Royal Melbourne Hospital, Victoria 3050, Australia vii ... Vlll PARTICIPANTS S. J. JACOBS Wellcome Research Laboratories, Burroughs Wellcome Co., 3030 Cornwallis Road, Research Triangle Park, North Carolina 27709, USA C. R. KAHN The Josh Diabetes Center, 1 Josh Place, Boston, Mas- sachusetts 02215, USA J. G. KNIGHT MRC Autoimmunity Research Unit, Otago University Medical School, PO Box 913, Dunedin, New Zealand J. M. LINDSTROM The Salk Institute, PO Box 85800, San Diego, California 92138, USA S. McLACHLAN Department of Medicine, Wellcome Research Labor- atories, Royal Victoria Infirmary, Newcastle upon Tyne NEl 4LP, UK N. A. MITCHISON Tumour Immunology Unit, Department of Zoology, University College London, Gower Street, London WClE 6BT, UK J. NEWSOM-DAVIS Department of Neurological Science, The Royal Free Hospital, Pond Street, London NW3 2QG, UK M. A. RAFTERY Division of Chemistry and Chemical Engineering, The Chemical Laboratories, California Institute of Technology, Pasadena, California 91125, USA B. REES SMITH Department of Medicine, Welsh National School of Medicine, Heath Park, Cardiff CF4 4XN, UK M. RODBELL Institut de biochimie clinique, Sentier de la Roseraie, 1211 Genkve 4, Switzerland I. M. ROI'IT Department of Immunology, Arthur Stanley House, Middlesex Hospital Medical School, 40-50 Tottenham Street, London W1P 9PG. UK J. C. VENTER Department of Biochemistry, School of Medicine, State University of New York at Buffalo, 102 Cary Hall, Buffalo, New York 14214, USA A. VINCENT Department of Neurological Science, The Royal Free Hospital, Pond Street, London NW3 2QG, UK