The Immunoglobulins: Structure and Function

284 Pages·1998·14.34 MB·English

by  Roald Nezlin

The
Immunoglobulins
This Page Intentionally Left Blank
The
Immunoglobulins
STRUCTURE AND FUNCTION
ROALD NEZLIN
Department oj Immunology
The Weizmann Institute of Science
Rehovot, Israel
ACADEMIC PRESS
San Diego London Boston New York Sydney Tokyo Toronto
Front Cover Photograph: Courtesy of Dr. Alexander McPherson and Dr. Lisa Harris. Image based
on coordinates by Lisa J. Harris, Steven B. Larson, Karl W. Hasel, and Alexander McPherson
(1997). Refined structure of an intact IgG2a monoclonal antibody. Biochemistry 36, 1581-1597.
This book is printed on acid-free paper.
Copyright (cid:14)9 1998 by ACADEMIC PRESS
All Rights Reserved.
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Library of Congress Cataloging-in-Publication Data
Nezlin, R. S. (Roal 'd Solomonovich)
The immunoglobulins : structure and function / Roald Nezlin.
p. cm.
Includes bibliographical references and index.
ISBN 0-12-517970-7 (hc : alk. paper)
1. Immunoglobulins. I. Title
QR186.7.N489 1998
616.07'98--dc21 98-4750
CIP
PRINTED IN THE UNITED STATES OF AMERICA
98 99 00 01 02 03 MM 9 8 7 6 5 4 3 2 1
Contents
Preface xi
I
PA RT
Structural Aspects
1 General Characteristics of Immunoglobulin Molecules
I. Immunoglobulin Classes 4
A. Immunoglobulin G 5
B. Immunoglobulin M 6
C. Immunoglobulin A 7
D. Immunoglobulin D 9
E. Immunoglobulin E 9
II. Heterogeneity of Immunoglobulins 10
III. Detection and Isolation of Immunoglobulins 11
A. Detection of Immunoglobulins 11
B. Isolation of Immunoglobulins 12
IV. Proteolytic and Chemical Fragments of Immunoglobulins 13
A. Fragmentation by Proteinases 13
B. Chemical Fragmentation 16
V. Immunoglobulin Peptide Chains 17
A. General Features 17
B. Variable Regions 19
C. Constant Regions 21
VI. Additional Peptide Chains 28
A. J Chain 28
B. Secretory Component 29
vi Contents
C. Surrogate Chains on the B-Cell Precursors 31
D. Accessory Peptide Chains of the B-Cell Antigen
Receptor Complex 32
VII. Immunoglobulin Fold (Domain) 36
A. Structural Characteristics 36
B. Domains of Members of Immunoglobulin Superfamily 38
C. Contacts between Domains 40
VIII. Fab Portion 42
IX. Fc Portion 43
X. Immunoglobulin Molecules 43
A. Dissociation and Reassociation of Immunoglobulin
Peptide Chains 43
B. Intact Immunoglobulin Molecules 46
XI. Carbohydrate Components of Immunoglobulins 52
A. Linkage of Glycans to Immunoglobulin Peptide Chains 53
B. Chemical Structure of Immunoglobulin Glycans 54
C. Distribution of Glycans on Immunoglobulin Molecules 55
D. Three-Dimensional Studies of Immunoglobulin
Glycans 57
E. Functions of Immunoglobulin Carbohydrates 59
F. Variations of Galactosylation 60
References 62
2 Animal and Human Immunoglobulins
I. Low Vertebrates 76
A. Fishes 76
B. Amphibians 79
C. Reptiles 8O
II. Birds 81
A. Chickens 81
B. Ducks 82
III. Mammals 84
A. Laboratory Animals 84
B. Farm Animals 91
C. Pets 94
IV. Human Immunoglobulins 95
A. General Considerations 95
B. Human Allotypes 96
C. Human Immunoglobulin Genes 98
V. Origin of Antibody Diversity in Mice and Humans 100
A. V(D)J Recombination 102
B. Somatic Hypermutation 103
C. Class Switching 104
Contents vii
VI. Evolutionary Aspects 105
A. Immunoglobulin-Type Domains in Prokaryotes
and Invertebrates 105
B. Evolution of Immunoglobulin Domains 110
References 112
3 Engineering Antibody Molecules
I. Problems of Serum Immunotherapy 123
II. Chimeric Antibody Molecules and Humanization 125
III. Minimal Antibody Fragment (Fv) 127
IV. Production of Human Monoclonal Antibodies
by Phage-Display and Transgene Technologies 130
A. Phage-Display Technology 130
B. Transgenic Animals 133
V. Engineering of Immunoglobulins with Novel Properties 134
A. Fusion Proteins 134
B. Immunotoxins 136
VI. Polymerization of IgG Molecules and Their Fragments 137
VII. Bispecific Antibodies 139
References 142
PART I I
Functional Aspects
4 Antigen-Combining Site
I. General Characteristics 151
A. Canonical Conformations of Hypervariable Loops 152
B. Correlation of Binding Site Surface with Type of Antigen 161
C. Bonds between Antigen and Antibody 164
D. Residues Responsible for Contacts with Antigens 165
E. Water Molecules Participate in Antigen-Antibody Interactions 168
II. Conformational Changes Linked with Antigen Binding 169
A. Induced Fit 170
B. Global Changes 171
III. Complex of V H Domain of Camelid Heavy Chain Antibodies
with Antigen 172
IV. Interaction of an Autoantibody (Rheumatoid Factor)
with Fc 7 173
viii Contents
V. Structural Aspects of Antibody Specificity 174
A. Complexes of a Single Antibody with Several
Related Antigens 174
B. Complexes of a Single Epitope with Different Antibodies 176
C. Effect of Mutations on the Antigen-Combining Site 177
D. Structure of Idiotype--Anti-Idiotype Complexes 179
VI. Modeling Antibody-Combining Sites 182
A. Knowledge-Based Methods 184
B. ab initio Procedures 185
C. Application of Modeling 186
VII. Structural Aspects of Catalytic Antibody Activity 189
A. Catalytic Antibodies Induced by Immunization 189
B. Autoantibodies with Catalytic Activity 193
References 195
5 Antigen-Recognizing Molecules Other Than Antibodies
I. T-Cell Antigen Receptor 205
II. Proteins of Major Histocompatibility Complex 207
III. Complexes of T-Cell Receptor and Peptide-MHC 211
IV. CD1 Molecules 212
V. Natural Killer Cell Inhibitory Receptors 213
VI. Comparison of Antigen Binding by Various
Antigen-Recognizing Molecules 215
References 216
6 Interactions Outside the Antigen-Combining Site
I. Fc Receptor-Binding Sites 221
A. Binding Sites for Fc Receptors Involved in Effector Responses 223
B. Binding Sites for Fc Receptors Involved in Transcytosis 227
II. Complement-Binding Sites 230
A. C lq Binding 231
B. C3b and C4b Binding 234
C. C3a, C4a, and C5a Anaphylatoxin Binding 234
III. Proteins Reacting with the Fc Portion 235
A. Clusterin 235
B. Human Plasma Glycoprotein 60 235
C. Fibronectin 235
D. Fc-Binding Peptides 236
E. Seminal Proteins 236
E G-Actin 237
G. Placental Alkaline Phosphatase 237
H. Herpes Simplex Virus Proteins 237
Contents ix
IV. Proteins Reacting with the Fab Portion 237
A. Prolactin 237
B. Protein Fv 238
C. T-Cell Protein CD4 238
D. HIV Protein gp120 239
V. Lectins 239
VI. Molecular Chaperones 241
VII. Bacterial Immunoglobulin-Binding Proteins 243
A. Staphylococcal Protein A 243
B. Streptococcal Protein G 245
C. Protein H 247
D. Protein L 247
References 247
7 Segmental Movements of Immunoglobulin Molecules
I. General Aspects 255
II. Functional Aspects of Segmental Flexibility 259
References 261
Index 263