Antibodies and T-Cell Receptors,

551 Pages·1996·32.08 MB·English

by  Edgar Haber

ADVANCES IN PROTEIN CHEMISTRY
Volume 49
Antigen Binding Molecules: Antibodies and T-cell Receptors
This Page Intentionally Left Blank
ADVANCES IN
PROTEIN CHEMISTRY
EDITED BY
FREDERIC M. RICHARDS DAVID E. EISENBERG
Department of Molecular Biophysics Department of Chemistry and Biochemistry
and Biochemistry University of California, Los Angeles
Yale University Los Angeles, California
New Haven, Connecticut
PETER S. KIM
Department of Biology
Massachusetts Institute of Technology
Whitehead lnstitute for Biomedical Research
Howard Hughes Medical lnstitute Research Laboratories
Cambridge, Massachusetts
VOLUME 49
Antigen Binding Molecules:
Antibodies and T-cell Receptors
EDITED BY
EDGARHABER
Department of Biological Sciences
Harvard School of Public Health
Harvard Medical School
Boston, Massachusetts
ACADEMIC PRESS
San Diego London Boston
New York Sydney Tokyo Toronto
@
This book is printed on acid-free paper.
Copyright 0 1996 by ACADEMIC PRESS
All Rights Reserved.
No part of this publication may be reproduced or transmitted in any form or by any
means, electronic or mechanical, including photocopy, recording, or any information
storage and retrieval system, without permission in writing from the publisher.
Academic Press, Inc.
525 B Street, Suite 1900, San Diego, California 92101-4495, USA
http:lfwww.apnet.com
Academic Press Limited
24-28 Oval Road, London NWl 7DX, UK
http://www.hbuk.co.uk/ap/
International Standard Serial Number: 0065-3233
International Standard Book Number: 0-1 2-034249-9
PRINTED IN THE UNITED STATES OF AMERICA
96 97 9899 00 01BC 9 8 7 6 5 4 3 2 1
To the memory of Christian B. Anfinsen,
without whose insights into the structure of
protein molecules much of what is written
here could not have been accomplished.
This Page Intentionally Left Blank
CONTENTS
PREFACE . . . . . . . . . . . . . xi
Antigen-Specific T-cell Receptors and Their Reactions with
Natural Complexes Formed by Peptides with Major
Histocompatibility Complex Proteins
HERMANN. EISENY, URIS YKULEAVN,D THEODJO. RTSEO MIDES
I. Overview . . . . . . . . . . . 1
11. History and Background . . . . . . . . 3
111. T-cell Receptor Genes . . . . . . . . 8
IV. T-cell Receptor Proteins . . . . . . . . 11
V. T-cell Receptor Ligands: Peptide-MHC Complexes . 15
VI. T-cell Responses to PepMHC . . . . . . 22
VII. T-cell Receptor Accessory Proteins . . . . . 39
VIII. Altered Peptide Ligands: Partial Agonists and
Antagonists . . . . . . . . . . . 41
IX. MHC Restriction by Self and Nonself MHC: Paradox of
Alloaggression . . . . . . . . . . 43
X. Concluding Remarks . . . . . . . . 47
References . . . . . . . . . . . 48
X-Ray Crystallography of Antibodies
EDUARDAO. PADUN
I. Introduction . . . . . . . . . . 57
11. X-Ray Crystallography of Whole Antibodies . . . 68
111. X-Ray Crystallography of Fc . . . . . . . 74
IV. X-Ray Crystallography of Antigen Binding Fragments . 79
V. X-Ray Crystallography of Complexes of Antibodies with
Specific Ligand . . . . . . . . . . 87
VI. Conclusions . . . . . . . . . . . 125
References . . . . . . . . . . . 128
...
Vlll CONTENTS
Insight into Antibody Combining Sites Using Nuclear Magnetic
Resonance and Spin Label Haptens
HARDEMN. MCCONNEALNLD MARIAM ARTINEZ-YAMOUT
I. Introduction . . . . . . . . . . 135
11. Antibodies ANOn . . . . . . . . . 136
111. Difference Spectra . . . . . . . . . 138
IV. Selective Deuteration . . . . . . . . 138
V. NMRSignalAssignments . . . . . . . 139
VI. Diamagnetic Haptens . . . . . . . . 14 1
VII. Distance Titrations . . . . . . . * . 143
VIII. Combining Site Dynamics and Reaction Kinetics . . 143
IX. Crystal Structure ofAN02 . . . . . * . 144
X. Conformational Heterogeneity . . . . . . 145
XI. Synopsis and Outlook . . . . . . . . 147
References . . . . . . . . . . . 148
Computational Biochemistry of Antibodies and T-cell Receptors
JIRI NOVOTNAYND JURCEN BAJORATH
I. Background . . . . . . . . . . 150
11. Tools of Computer Analysis . . . . . . 154
111. Structures, Sequences, and Superfamilies . . . 162
IV. Molecular Anatomy of Antibody Binding Site . . 168
V. In Search of Effector Sites . . . . . . 173
VI. Protocols for Three-Dimensional Modeling of Binding
Sites . . . . . . . . . . . 177
VII. Binding Affinity and Specificity . . . . . 194
VIII. Molecular Basis of Protein Antigenicity . . . 213
IX. Antibody Engineering . . . . . . . 220
X. T-cell Receptor Modeling and Engineering . . 232
References . . . . . . . . . . 236
Catalytic Antibodies
EDWARMD. DRICCERANSD PETERG . SCHULTZ
I. Introduction . . . . . . . . . 261
11. Immunological Evolution of Catalysis . . . . 262
111. Structural Studies . . . . . . . . 266
CONTENTS ix
IV. Evolving Functions Not Yet Found in Nature . . . 270
V. Unnatural Cofactors . . . . . . . . . 273
VI. Difficult ChemicalTransformations . . . . . 275
VII. Future Directions . . . . . . . . . 280
VIII. Conclusion . . . . . . . . . . . 283
References . . . . . . . . . . . 284
The Nature of the Antigen
MICHAESLE LAAN D ISRAEPLE CHT
I. Introduction . . . . . . . . . . 289
11. Antigens, Antigenicity, Immunogenicity . . . . 290
111. Molecular Criteria forhtigenicity . . . . . 298
IV. Role ofConformation inhtigenicity . . . . . 300
V. Antibody-Antigenic Epitope Interactions . . . . 303
VI. Conformational Transitions Induced by Hapten
Binding . . . . . . . . . . . . 306
VII. T-Cell-Antigenic Epitope Interactions . . . . . 31 1
VIII. Thymus-Independent Antigens . . . . . . 316
IX. Superantigens . . . . . . . . . . 319
X. Tumor Antigens . . . . . . . . . . 32 1
XI. Concluding Remarks . . . . . . . . 323
References . . . . . . . . . . . 323
Antibody Binding Sites
JAMES S. HUSTONM, ICHAELN . MARGOLIEASN, D EDGAHRA BER
I. Overview . . . . . . . . . . . 330
11. Protein Chemistry of Antibody Fragments and Antigen
Binding Regions . . . . . . . . . . 330
111. Engineered Antibody Binding Sites . . . . . 347
IV. Antibody Combining Site Structure: Antiarsonate and
Antidigoxin Antibodies . . . . . . . . 380
V. Enhancing Enzyme Selectivity with Substrate-Selective
Antibodies . . . . . . . . . . . 427
References . . . . . . . . . . . 439