Molecular Mechanisms of Immunological Self-Recognition

Molecular Mechanisms of Immunological Self-Recognition

1st Edition - February 11, 1993

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  • Editors: Frederick W. Alt, Henry J. Vogel
  • eBook ISBN: 9781483215938

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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




Product details

  • No. of pages: 274
  • Language: English
  • Copyright: © Academic Press 1993
  • Published: February 11, 1993
  • Imprint: Academic Press
  • eBook ISBN: 9781483215938

About the Editors

Frederick W. Alt

Frederick W. 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

Professor of Pediatrics and Professor of Genetics, Harvard Medical School, Boston, MA, USA

Henry J. Vogel

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