Table Of ContentImmunobiology 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.
The use of general descriptive names, trade names, trademarks, etc. in this publication, even if the
former are not especially identified, is not to be taken as a sign that such names, as understood by
the Trade Marks and Merchandise Marks Act, may accordingly be used freely by anyone.
While the advice and information in this book are believed to be true and accurate at the date of
going to press, neither the authors nor the editors nor the publisher can accept any legal responsibility
for any errors or omissions that may be made. The publisher makes no warranty, express or implied.
with respect to the material contained herein.
Permission to photocopy for internal or personal use, or the internal or personal use of specific
clients, is granted by Springer-Verlag New York Inc. for libraries registered with the Copyright
Clearance Center (CCC), provided that the base fee of $0.00 per copy, plus $0.20 per page is paid
directly to CCC, 21 Congress Street, Salem, MA 01970, USA. 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
