Table Of ContentContributors
JOSEPH P. BROWN
JEAN-CHARLES CEROTTINI
KARL ERIK HELLSTRÖM
PETER J. LACHMANN
GÉRARD LUFFAU
PETER PERLMANN
PIERRE PERY
The Antigens
VOLUME V
EDITED BY
MICHAEL SELA
Department of Chemical Immunology
The Weizmann Institute of Science
Rehovot, Israel
ACADEMIC PRESS New York San Francisco London 1979
A Subsidiary of Harcourt Brace Jovanovich, Publishers
COPYRIGHT © 1979, BY ACADEMIC PRESS, INC.
ALL RIGHTS RESERVED.
NO PART OF THIS PUBLICATION MAY BE REPRODUCED OR
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United Kingdom Edition published by
ACADEMIC PRESS, INC. (LONDON) LTD.
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Library of Congress Cataloging in Publication Data
Sela, Michael,
The antigens.
Includes bibliographies.
1. Antigens and antibodies. 2. Immunochemistry.
1. Arnheim, Norman. II. Title. [DNLM: 1. Antigens.
2. Immunochemistry. QW570 A629 1973]
QR186.5.S44 574.2'92 73-799
ISBN 0-12-635505-3
PRINTED IN THE UNITED STATES OF AMERICA
79 80 81 82 9 8 7 6 5 4 3 2 1
List of Contributors
Numbers in parentheses indicate the pages on which the authors' contributions begin.
JOSEPH P. BROWN (1), Division of Tumor Immunology, Fred Hutch-
inson Cancer Research Center, Department of Pathology, Uni
versity of Washington, Seattle, Washington 98104
JEAN-CHARLES CEROTTINI (173), Unit of Human Cancer Immunol
ogy, Ludwig Institute for Cancer Research, CH-1066 Epalinges
S/ Lausanne, Switzerland
KARL ERIK HELLSTRÖM (1), Division of Tumor Immunology, Fred
Hutchinson Cancer Research Center, Department of Pathology,
University of Washington, Seattle, Washington 98104
PETER J. LACHMANN (283), MRC Group on Mechanisms in Tumour
Immunity, The Medical School, Cambridge CB2 2QH, England
GÉRARD LUFFAU (83), Station de Recherches de Virologie et d'Im
munologie, 78850-Thiverval-Grignon, France
PETER PERLMANN (173), Department of Immunology, University of
Stockholm, S-10691 Stockholm, Sweden
PIERRE PERY (83), Station de Recherches de Virologie et d'Immunol
ogie, 78850-Thiverval-Grignon, France
Preface
This is the fifth volume of a comprehensive treatise that covers all
aspects of antigens and related areas of immunology, focusing atten
tion on the chemistry and biology of antigens as well as on their im
munologie role and expression. In the six years since Volume I was
published, immunology has significantly progressed and the increase
in fundamental knowledge is, by now, reflected in major medical ap
plications. At the same time, heightened expectations from the fruits
of immunology place an ever heavier responsibility on immunologists.
The four chapters of Volume V arte concerned with four complex
problems of direct relevance to human health.
Immunodiagnosis and immunotherapy have acquired a central im
portance in our efforts to combat cancer, and an intimate knowledge
of tumor antigens has become a sine qua non for any real progress in
this field. The chapter devoted to this subject is therefore of consid
erable topical importance, as is true also for the chapter on antigens
of helminths which are related to some of the most prevalent parasitic
diseases. The third chapter deals with cytotoxic lymphocytes and the
various mechanisms involved in cell-mediated immune reactions so
profoundly instrumental in the rejection of allografts, in the destruc
tion of certain tumors, and in the causing of tissue injuries in many
autoimmune diseases or in viral infections. Complement is the name
of one of the most fascinating systems in biology, a system so com
plex that for many years it defied understanding. As is clearly shown
in the chapter devoted to this subject, not only have its components
been defined but both the classic and the alternative pathway of com
plement activation are now, to a great extent, clarified.
It is a pleasure to acknowledge, also on this occasion, the whole
hearted cooperation of the staff of Academic Press in the preparation
of this treatise.
MICHAEL SELA
ix
Contents of Other Volumes
Volume I
Nucleic Acid Antigens
B. David Stollar
Immunochemistry of Enzymes
Ruth Arnon
Structure of Immunoglobulins
Joseph A. Gaily
Immunoglobulin Allotypes
Rose Mage, Rose Lieberman, Michael Potter, and William D. Terry
The Evolution of Proteins
Norman Arnheim
Phylogeny of Immunoglobulins
R. T. Kubo, B. Zimmerman, and H. M. Grey
Chemistry and Biology of Immunoglobulin E
Kimishige Ishizaka
AUTHOR INDEX—SUBJECT INDEX
Volume II
Protein Antigens: The Molecular Bases of Antigenicity and
Immunogenicity
Michael J. Crumpton
xi
xii Contents of Other Volumes
Blood Group Antigens
Sen-itiroh Hakomori and Akira Kobata
Low Molecular Weight Antigens
A. L. de Weck
The Application of Antibody to the Measurement of Substances of
Physiological and Pharmacological Interest
Edgar Haber and Knud Poulsen
Idiotypy of Antibodies
Jacques Oudin
Immunoglobulin A
J. F. Heremans
AUTHOR INDEX—SUBJECT INDEX
Volume III
Microbial Polysaccharides
Klaus Jann and Otto Westphal
Antigenic Determinants and Antibody Combining Sites
Joel W. Goodman
Lymphocytic Receptors for Antigens
G. L. Ada and P. L. Ey
Allergens and the Genetics of Allergy
David G. Marsh
A Biologic and Chemical Profile of Histocompatibility Antigens
S. Ferrone, M. A. Pellegrino, and R. A. Reisfeld
Antigens of the Mycoplasmatales and Chlamydiae
George E. Kenny
Virus Infections and the Immune Responses They Elicit
William H. Burns and Anthony C. Allison
AUTHOR INDEX—SUBJECT INDEX
Contents of Other Volumes xiii
Volume IV
Immune Reactions of Lipids and Lipid Model Membranes
Carl R. Alving
Immunology of the Antibiotics
Janet M. Dewdney
Protective Antigens of Bacteria
E. J. Steele, C. R. Jenkin, and D. Rowley
Antigens of Pathogenic Fungi
S. B. Salvin and Ruth Neta
Antigenic Competition
Michael J. Taussig
Adjuvants
Felix Borek
Lectins: Their Chemistry and Application to Immunology
Halina Lis and Nathan Sharon
AUTHOR INDEX—SUBJECT INDEX
CHAPTER1
Tumor Antigens
KARL ERIK HELLSTRÖM AND JOSEPH P. BROWN
I. Introduction 2
II. Classic Studies of Tumor-Specific Transplantation Antigens . . 3
III. Detection of Tumor Antigens 6
A. Transplantation Tests 6
B. Tests of Cellular Cytotoxicity in Vitro 7
C. Other Tests of Cellular-Immunity 9
D. Serological Tests 9
Ε. Immunization 12
IV. Purification of Tumor Antigens 14
A. Plasma Membrane Purification 14
B. SolubilizationofCSA 15
C. Biochemical Purification of CSA 17
D. Immunochemical Purification of CSA 18
Ε. Structural Studies of Tumor Antigens 20
V. Nature of Tumor Antigens . 20
A. Antigens Induced by DNA Tumor Viruses . . . . 20
B. Antigens Induced by RNA Tumor Viruses . . .. 23
C. Differentiation Antigens 26
D. Unique TSTA of Chemically Induced Tumors . . .. 31
Ε. Glycolipids as TAA 33
VI. The Immune Response to Tumor Antigens 34
A. Humoral Immunity to Tumor Antigens 34
B. Cell-Mediated Immunity to Tumor Antigens . . .. 36
VII. The Role of Tumor Antigens in the Escape of Tumors from
Immunological Control 39
A. Evidence That Tumor Antigen Can Inhibit ("Block")
Cell-Mediated Cytotoxicity in Vitro 39
B. The Role of Tumor Antigen in Facilitating Tumor Growth
in Vivo 43
C. Some Other Mechanisms by Which Antigenic Tumor Cells
Can Escape from Immunological Control 46
VIII. Human Tumor Antigens 47
A. Serological Studies with Heteroantisera 48
B. Serological Studies with Sera from Tumor Patients . .. 51
C. Cell-Mediated Reactivity to Human Tumor Antigens . . 54
IX. Conclusions 65
References 66
1
THE ANTIGENS, VOL. V
Copyright © 1979 by Academic Press, Inc.
All rights of reproduction in any form reserved.
ISBN 0-12-635505-3
2 Karl Erik Hellström and Joseph P. Brown
I. Introduction*
As early as the beginning of this century, Ehrlich speculated that
tumors might be recognized as antigenically foreign by their hosts and
that immunology might one day contribute to the prevention and
treatment of cancer (Himmelweit, 1957). Before long a number of in
vestigators claimed, that animal experiments supported this. Their
claims were mostly based on the observation that animals immunized
with a transplantable tumor rejected a subsequent graft ofthat tumor.
With the benefit of hindsight we can now see that the alleged tumor
immunity was probably the outcome of reactivity to alloantigens
rather than to tumor-specific antigens, since the animals used in these
early studies were not inbred. When this was realized, tumor immu
nology fell into disrepute (Woglom, 1929).
The development of inbred strains of mice, in which tissues could
be grafted without rejection, set the stage for a new approach to tumor
immunology. Gorer (1956) showed that some syngeneic mouse leu-
kemias expressed foreign cell surface antigens (CSA). Gross (1943),
Foley (1953), Prehn and Main (1957), and others showed that mice im
munized with a syngeneic chemically induced tumor could reject a
graft of the immunizing tumor; the antigens responsible for rejection
of syngeneic tumors are now commonly referred to as tumor-specific
transplantation antigens (TSTA). Sjögren et al. (1961a,b) and Habel
(1961, 1962) then demonstrated that tumors of a common viral etiology
had cross-reacting TSTA.
During the years that have passed since the first solid evidence for
tumor antigens was obtained, such antigens have been demonstrated
in a variety of animal neoplasms. As yet, however, little is known
about their nature. Some antigens appear to be truly tumor specific,
for example, the individually unique TSTA of chemically induced
* Abbreviations: ADCC, antibody-dependent cellular cytotoxicity; AFP, a-fetopro-
tein; B cells, bone marrow-derived lymphocytes with surface immunoglobulin; CEA,
carcinoembryonic antigen; CSA, cell surface antigen; EBNA, Epstein-Barr virus nu
clear antigen; EBV, Epstein-Barr virus; FeLV, feline leukemia virus; FeSV, feline sar
coma virus; FOCMA, feline oncornavirus-associated cell membrane antigen; GCSA,
Gross virus-associated cell surface antigen; K cell, killer cell (effector cell in ADCC);
MCA, 3-methylcholanthrene; MCSA, Moloney cell surface antigen; MHC, major histo-
compatability complex; MSV, murine sarcoma virus; MTV, mammary tumor virus;
MuLV, murine leukemia virus; NK cell, natural killer cell; NP-40, Nonidet P-40; OFA,
oncofetal antigen; PAGE, polyacrylamide gel electrophoresis; SBF, specific blocking
factors; SDS, sodium dodecyl sulfate; SV40, simian virus 40; TAA, tumor-associated an
tigen; T cell, thymus-processed lymphocyte; ts mutant, temperature-sensitive mutant;
TSTA, tumor-specific transplantation antigen; uv, ultraviolet light.
