Molecular Mechanisms of Immunological Self-Recognition - 1st Edition - ISBN: 9780120537501, 9781483215938

Molecular Mechanisms of Immunological Self-Recognition

1st Edition

Editors: Frederick Alt Henry J. Vogel
eBook ISBN: 9781483215938
Imprint: Academic Press
Published Date: 11th February 1993
Page Count: 274
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Description

Molecular Mechanisms of Immunological Self-Recognition covers the understanding of immunological self-recognition. The introductory chapter of the book summarizes the dawn of the insight into immunological tolerance, and provides an overview of research on the underlying mechanisms. The book addresses the developments in the molecular mechanisms of B and T cell tolerance and describes the failure of tolerance in autoimmunity. The text concludes by furnishing orienting perspectives and highlighting new information presented. The novel findings characterized as impressive advances pertain to the areas of B cell development and the generation of molecular diversity; V gene usage, especially from transgenes, in positive and negative thymic selection; the handling of positive and negative signals by T and B cells; anergy in postthymic T cells; the design of peptide-based therapy for autoimmune diseases; and the design of therapy with the aid of monoclonal antibodies. Immunologists will find the text useful.

Table of Contents


Preface

Part I Introduction

1 Immunological Tolerance Revisited in the Molecular Era

The Dawn of Immunologic Tolerance

One Cell-One Antibody, and Implications

In Vitro Lymphocyte Cloning Techniques Validate Repertoire Purging as a Tolerance Mechanism; Clonal Abortion versus Clonal Anergy

Clonal Abortion and Clonal Anergy Come of Age in the Molecular Era

The Genesis of High-Affinity Antibodies

Soluble Antigen Can Cause Adult Tolerance, Including a Failure of Appearance of High-Affinity B Cells

Summary and Conclusions

References

Part II B Cell Tolerance

2 Mechanisms and Meaning of B Lymphocyte Tolerance

Introduction

The Deletion-Anergy Decision

Consequences of Deletion versus Anergy

References

3 Tolerant Autoreactive B Lymphocytes in the Follicular Mantle Zone Compartment: Substrates for Receptor Editing and Reform

Introduction

Localization of Transgene-Expressing B Cells within Peripheral Lymphoid Organs

Timing of Tolerance Induction during Bone Marrow B Cell Differentiation

Recovery from Receptor Modulation and Tolerance

Deletion or Anergy?

Does the Follicular Mantle Zone Serve as a "Reform School" for Wayward B Cells?

References

Part III Lymphocyte Signaling

4 T Cell Anergy

Introduction

Cellular Characteristics

Biochemical Events Resulting from TCR Occupancy

Reversal of Anergy

Conclusion

References

5 The T Cell Antigen Receptor: Biochemical Aspects of Signal Transduction

Introduction

Substrate Analysis in Murine and Human T Cells; Possible Tyrosine Kinase Regulation of Phospholipase C

Analysis of Tyrosine Phosphatases

The Serine Kinase Pathway

FYN Is a T Cell Receptor-Associated Tyrosine Kinase

References

6 Structure and Signaling Function of B Cell Antigen Receptors of Different Classes

Introduction

Results

References

Part IV T Cell Tolerance

7 Self-Nonself Discrimination by T Lymphocytes

Introduction

Negative and Positive Selection of a Transgenic Receptor Specific for the Male-Specific Peptide Presented by Class I H-2Db MHC Molecules

Lack of Allelic Exclusion of the a TCR Chain in αß TCR Transgenic Mice

Mutations in the Peptide-Binding Groove of MHC Molecules Affect Antigenicity and Negative as Well as Positive Selection

Positive Selection: Expansion of Mature Thymocytes or Maturation of Immature Thymocytes?

Postthymic Expansion of Mature T Cells

Postthymic Tolerance

Discussion

References

8 Transgenic Mouse Model of Lymphocyte Development

Introduction

T Cell Receptor Transgenic Mouse as a Model System to Study T Lymphocyte Development

Clonal Deletion of Self-Reactive T Cells

Positive Selection Model of the Origin of MHC-Restricted T Cells

Molecular Requirements for Positive Selection

Future Issues in T Cell Development Using TCR Transgenic Mice

References

9 Recognition Requirements for the Positive Selection of the T Cell Repertoire: A Role of Self-Peptides and Major Histocompatibility Complex Pockets

Introduction

Results and Discussion

Summary

References

10 Mechanisms of Peripheral Tolerance

Introduction

Results

Distinct Mechanisms of Peripheral Tolerance

Conclusions

References

11 An Analysis of T Cell Receptor-Ligand Interaction Using a Transgenic Antigen Model for T Cell Tolerance and T Cell Receptor Mutagenesis

Introduction

T Cell Receptor Mutagenesis

A Paired Antigen/TCR Transgenic System

References

12 T Cell Repertoire and Tolerance

Introduction

Superantigens

Tolerance to Self-Superantigens Shapes the T Cell Repertoire

Vβ Interaction with the Self-Superantigen Mls-la

Vβ Interaction with the Foreign Superantigens

References

13 Sequential Occurrence of Positive and Negative Selection during T Lymphocyte Maturation

Introduction

Results and Discussion

References

14 Tolerance Induction in the Peripheral Immune System

Introduction

Materials and Methods

Results

Discussion

References

Part V Autoimmunity

15 Activation-Induced Cell Death of Effector T Cells: A Third Mechanism of Immune Tolerance

Introduction

Experimental Results

Interpretations

References

16 T Cells Involved in Inductive Events in the Pathogenesis of Autoimmune Diabetes Mellitus

Text

References

17 Genetic Control of Diabetes and Insulitis in the Nonobese Diabetic Mouse: Analysis of the NOD.H-2b and B10.H-2nod^ Strains

Introduction

Materials and Methods

Results and Discussion

Concluding Remarks

References

18 Islet Tolerance in Humans and Transgenic Mice

Text

References

19 Fluorescence-Activated Cell Sorter Analysis of Peptide-Major Histocompatibility Complex

Introduction

FACS Binding Assay

Results

Discussion

References

20 Tolerance to Self: A Delicate Balance

Introduction

Monoidiotypy

TCR-Specific Antibody Modulation of Disease

TCR Peptide Modulation

Discussion

References

21 Prevention, Suppression, and Treatment of Experimental Autoimmune Encephalomyelitis with a Synthetic T Cell Receptor V Region Peptide

Introduction

Animal Studies

Human Studies

Summary

References

Part VI Perspectives

22 Tolerance of Self: Present and Future

The 1975 Baseline

F Liver Antigen

Negative Signaling

Anergy, and the Need for a Defined Anergic Phenotype

Thymus Lobe Cultures

Autoimmunity and Epitope Linkage

Toward Gene Therapy in Autoimmunity

References

Index




Details

No. of pages:
274
Language:
English
Copyright:
© Academic Press 1993
Published:
Imprint:
Academic Press
eBook ISBN:
9781483215938

About the Editor

Frederick Alt

Frederick Alt

Frederick W. Alt is a Howard Hughes Medical Institute (HHMI) Investigator and Director of the Program in Cellular and Molecular Medicine (PCMM) at Boston Children's Hospital (BCH). He is the Charles A. Janeway Professor of Pediatrics and Professor of Genetics at Harvard Medical School. He works on elucidating mechanisms that generate antigen receptor diversity and, more generally, on mechanisms that generate and suppress genomic instability in mammalian cells, with a focus on the immune and nervous systems. Recently, his group has developed senstive genome-wide approaches to identify mechanisms of DNA breaks and rearrangements in normal and cancer cells. He has been elected to the U.S. National Academy of Sciences, the U.S. National Academy of Medicine, and the European Molecular Biology Organization. His awards include the Albert Szent-Gyorgyi Prize for Progress in Cancer Research, the Novartis Prize for Basic Immunology, the Lewis S. Rosensteil Prize for Distinugished work in Biomedical Sciences, the Paul Berg and Arthur Kornberg Lifetime Achievement Award in Biomedical Sciences, and the William Silan Lifetime Achievement Award in Mentoring from Harvard Medical School.

Affiliations and Expertise

Harvard Medical School, Boston, MA, USA

Henry J. Vogel

Ratings and Reviews