Immunobiology of HLA Bo Dupont Editor Immunobiology ofHLA Volume I Histocompatibility Testing 1987 With 362 Illustrations Springer-Verlag New York Berlin Heidelberg London Paris Tokyo Hong Kong 80 Dupont Member, Sloan-Kettering Institute for Cancer Research; Professor of Immunology Cornell University Graduate School of Medical Science New York, New York 10021, USA Library of Congress Cataloging-in-Publication Data Immunobiology of HLA / Bo Dupont, editor. p. cm. Proceedings of the Tenth International Histocompatibility Workshop and Conference, held in Princeton, N.J. and New York City, Nov. 12-23, 1987. Dedicated to the memory of Ruggero Ceppellini. Contents: v. I. Histocompatibility testing 1987 - v. 2. Immunogenetics and histocompatibility. Includes bibliographies and indexes. I. Histocompatibility testing-Congresses. 2. HLA histocompatibility antigens-Congresses. I. Dupont, Bo. II. Ceppellini, Ruggero. III. International Histocompatibility Workshop and Conference (lOth: 1987: Princeton, N.J. and New York, N.Y.) [DNLM: I. Histocompatibility Testing-congresses. 2. HLA Antigens-immunology-congresses. WO 680 13237 1987] QR187.H57I45 1989 616.07'9-dc19 DNLM/DLC 88-39761 © 1989 by Springer-Verlag New York Inc. All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer-Verlag, 175 Fifth Avenue, New York, NY 10010, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. 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Special requests should be addressed directly to Springer-Verlag New York, 175 Fifth Avenue, New York, NY 10010, USA, ISBN 0-387-96826-111989 $0.00 + 0.20. Typeset by Publishers Service, Bozeman, Montana. Printed and bound by Arcata Graphics/Halliday, West Hanover, Massachusetts. Printed in the United States of America. 9 8 7 6 5 4 3 2 I ISBN-13: 978-1-4612-8154-2 e-ISBN-13: 978-1-4612-3552-1 DOl: 10.1007/978-1-4612-3552-1 Dedication If this is my day of harvest, in what fields have I sowed the seed, and in what unremembered seasons? If this indeed be the hour in which I lift up my lantern, it is not my flame that shall burn therein. Kahlil Gibran Courtesy of C. Zmijewski. Ruggero Ceppellini died on May 5, 1988, after many months of struggle against lung cancer. His death leaves everyone, who knew him as a person or through his writings, with sadness and with an awareness of great loss. It was natural for Ceppellini, an innovator and problem solver in genetics, to synthesize new concepts from observations in different fields of science that appeared to have little relationship to each other. Above all he scored by applying his quantitative sense as a biometrician to problems posed to him by colleagues who did not think in terms of segre gation analysis or quantitative variation. Ceppellini was to immunogenetics what Mozart was to the keyboard, revelling in its virtuosity, ever fresh and new in the variety of concepts. He threw away in casual conversation ideas that others would have hoarded as v prize-winning treasures. Ceppellini had good insight into his own relationship with others. He knew he was headstrong and abrasive; he referred to himself-and to the rest of our little clique in the field-as a Baron. He loved center stage and could occupy that position for hours, sometimes mainly to retaliate against mediocrity, but always to stimulate and to enlighten. A man who could not lecture because his broken arm was in a plaster cast, a racing driver in a rented car, a genius, a friend-Ruggero. We were with you from the beginning, when youth affected our resolve with meaningful moments of living and toasted to joy, our main goal! You are amongst us, even today after the enemy of life destroyed the body but not the spirit and mind . You once said that living is learning to ask questions and obtain answers: the interminable sequence of science and experimenting and that, we are bound to grow old, to seed, struggle, enjoy and harvest. To leave an imprint and fold following a road with burning lanterns . Keep the lights bright and do not cease to focus your designs and objectives to conquer genetic basis of disease and embellish our incentives. "My life stopped too soon when I still filled front stage, wanting to be here with you and to live to old age. Why visit me at this place of my source, where we come to rest? There is nothing but empty space without bright figures of life's zest. There is no reason to mourn. Rejoice our moment, this moment when your hearts and voices stop all of life's torments." We wish your return from your dreams at dawn near the sun with vigorous songs to overcome exhaustion. Raise your cup and sip the wine many times mixed with storms, elegance and love, to combine with labour to discover the unknown. Oh traveler of the clouds, from distant constellations, vi dispeller of unfulfilled wishes and ephemeral illusions. Your arrival was heralded by music and lightning from igniting moons and stars flowers and tunes of spring. We remember your profile, the voice and its force its thunder and sty Ie and the unyielding course. But, why must we be deprived of your luminous guide with relentless passion, a force to give us pride? Our hearts trembling and our eyes blurred by tears. Life is nothing but continuing to learn to face our fears . Farewell our friend! Your spirit remains unchanged by memories and feelings unbend, of energy and unparalleled mind . . Edmund Yunis and Bernard Amos vii International Histocompatibility Workshop Council Chairman B. Dupont. New York, New York, USA Presidents E.D. Albert, Munich, Federal Republic of Germany W. Mayr, Vienna, Austria Past Presidents D.B. Amos, Durham, North Carolina, USA 1.1. Van Rood, Leiden, the Netherlands R. Ceppellini, Turin, Italy 1. Dausset, Paris, France F. Kissmeyer-Nielsen, Aarhus, Denmark W.F. Bodmer, London, United Kingdom P.1. Terasaki, Los Angeles, California, USA Councillors M. Aizawa, Sapporo, lapan F. Bach, Minneapolis, Minnesota, USA H. Bashir, Sydney, Australia 1.R. Batchelor, London, United Kingdom 1.G. Bodmer, London, United Kingdom C.B. Carpenter, Boston, Massachusetts, USA L. Degos, Paris, France C. Engelfriet, Amsterdam, the Netherlands H. Festenstein, London, United Kingdom P. Ivanyi, Amsterdam, the Netherlands Z. Layrisse, Caracas, Venezuela P.l. Morris, Oxford, United Kingdom R. Payne, Stanford, California USA A. Piazza, Torino, Italy P. Rubenstein, New York, New York, USA A. Svejgaard, Copenhagen, Denmark E.l. Thorsby, Oslo, Norway R. Tosi, Rome. Italy K. Tsuji, Isehara. lapan R. Walford, Los Angeles, California, USA E.l. Yunis. Boston, Massachusetts, USA IX Organizing Committee Chairman B. Dupont, New York, New York, USA Data Analysis 1.M. Lalouel, Salt Lake City, Utah, USA Serology E.L. Milford, Boston, Massachusetts, USA E.l. Yunis, Boston, Massachusetts, USA Biochemistry I S.Y. Yang, New York, New York, USA Biochemistry II R.W. Knowles, New York, New York, USA T-Cell I 1.A. Hansen, Seattle, Washington, USA T-Cell II N. Flomenberg, New York, New York, USA Southern Blot D. Cohen, Paris, France cDNA 1.S. Lee, New York, New York, USA x Preface to Volume I The Tenth International Histocompatibility Workshop and Conference was held in Princeton, New Jersey and New York City, New York, in November 1987. The International Histocompatibility Workshops date back to 1964 when D. Bernard Amos organized the first workshop on the HLA system for a small group of investigators who met at Duke University, North Carolina. The following nine workshops were held in 1965, 1967,1970, 1972, 1975, 1977, 1980, 1984, and 1987. These workshops have become a central and unifying forum for research and development in the field of human histocompatibility testing and immunogenetics. We have seen a rapid and sustained growth in active participation and involvement in this unique example of international collaborative research. Investigators from around the world have, for more than two decades, developed an open community, and lasting friendships have evolved. A sense of common goals, cooperative spirit, and mutual good will permeated not only the actual workshop and conference, but was also evident during the preceding three to four years of workshop planning and workshop studies. It has been evident since the early days of the first histocompatibility workshops that most of the scientific developments in the field of histocompatibility and immunogenetics occur outside the framework of the workshops. Many individual investigators have, dur ing the years, made the critical scientific contributions from which the histocompatibility community has benefitted. It has been, and continues to be, the responsibility of the International Histocompatibility Workshop Council to select the programmatic theme of each of the workshops. The past history of the workshops has clearly documented the symbiotic relationship between scientific progress in ba~ic immunogenetics and the timely selection of subject matters for these large collaborative research programs. The workshop concept has from time to time been challenged and the wisdom of con tinuing these very expensive and time-consuming projects has been questioned. Such concern is clearly legitimate and the question is also seriously considered prior to the organization of a new histocompatibility workshop. The decision to initiate the Tenth International Histocompatibility Workshop was made in Munich and Vienna in May 1984. I offered at that time to undertake the organization of the next workshop with the general programmatic subject, "The Molecular Genetic Basis for HLA Polymorphism. " The intent was to focus the attention of the histocompati bility testing community on modem techniques and approaches for biochemical, molecu lar genetic, and cellular analysis of HLA genes and gene products. One of the major goals of this workshop has been to develop a well-defined common source of HLA genes and gene products to be used as reference reagents. The panel of B-lymphoblastoid cell lines, now called the "Reference Panel of B-lymphoblastoid Cell Lines for Factors of the HLA System," consists of 107 cell lines, most of which are homozygous for HLA determinants. The B-cell lines and the DNA obtained from them constituted the central core around which most of the workshop studies evolved. These cell lines are now avail able to interested investigators and can be obtained from cell repositories in different parts of the world. The present publication, Immunobiology ofHLA, is divided into two volumes. Volume I, entitled Histocompatibility Testing 1987, contains the reports from the Tenth Interna tional Histocompatibility Workshop and describes the experimental designs of the work shop studies as well as the results obtained in these collaborative projects. It is our hope that this volume will serve as a practical guide in histocompatibility testing laboratories. The Joint Reports from the individual workshop components are presented in considerable detail, and the accompanying figures, tables, and pictures of gels from the biochemical studies, as well as Southern Blots, constitute an "Atlas for Factors of the HLA System." Volume II, entitled, Immunogenetics and Histocompatibility, contains 253 invited pa pers presented at the International Conference in New York City. We felt, however, that this volume would best serve as an up-to-date authoritative publication on molecular biology of the HLA system if the brief communications were supplemented with a series of review papers covering the major subjects in this rapidly evolving scientific field. Xl Volume II therefore consists of two parts: Part 1 contains six overview papers, and Part 2 contains the 253 brief communications. We hope this volume will serve as a useful handbook on the "state of the art" of basic research on HLA. The publication of lmmunobiology of HLA signals the completion of four years of a project which has engaged a large number of participants and involved 362 laboratories worldwide. The workshop meeting in Princeton had 412 active participants and more than 1,400 attended the Conference in New York City. The workshop studies required very substantial investments in manpower and laboratory resources by the participating laboratories. The involvement in this workshop has, for many participants, meant sacri fices of personal research objectives for the benefit of the global interest of our scientific community. The completion of this project has-as has always been the case-required that large and scientifically very productive laboratories be willing to participate and facilitate the technology transfer into laboratories with less experience. An endeavor of this magnitude and complexity necessitates this level of scientific cooperation. But this is precisely the uniqueness of the HLA community and the reason for the professional pride and friendship that is characteristic for our community. The credit for this tradition should be given to the founding members of the Interna tional Histocompatibility Workshops. I have felt it a great privilege to have been responsi ble for the present workshop project. As a member of a younger generation who has been welcomed and encouraged to contribute to this tradition, I felt throughout the last four years a strong commitment to implement the project in this spirit. We were all saddened when one of the original members of the HLA community, Ruggero Ceppellini, became seriously ill and recently died. We have decided to dedicate this publication to his memory. Ruggero was intensely interested in the scientific and clinical importance of the HLA system right up to his death. He frequently visited me throughout 1986-1987 and was keenly interested in how the workshop proceeded. He will be deeply missed. New York, New York, USA Bo Dupont Chairman Tenth International Histocompatibility Workshop and Conference XII