Molecular Mechanisms of Immunological Self-Recognition

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