Development of T Cell Immunity (eBook)

Front Cover 1
Molecular Biology andTranslational Science 4
Copyright Page 5
Contents 6
Contributors 12
The Development of T-Cell Immunity 14
Section I: The Evolution of T Cell Immunity 18
Chapter 1: Genome Duplication and T Cell Immunity 20
I Introduction 21
II WGD: From a Hypothesis to the Fact 23
III Roles of Ohnologs in Adaptive Immunity 25
IV Controversies Surrounding the Timing of WGD 35
V The AIS of Jawless Vertebrates 37
VI Concluding Remarks 42
Acknowledgments 42
References 42
Questions Arising from ‘‘Genome Duplication and T Cell Immunity’’ 50
Chapter 2: Response to Questions 51
I. Response to Question #1 51
II. Response to Question #2 51
References 52
Chapter 3: The Origin and Role of MHC Class I-Associated Self-Peptides 54
I. Key Features of the Adaptive Immune System 55
II. Genesis of the SMII 56
III. The Role of Constitutive Self-Peptide Presentation 61
References 65
Questions Arising from ‘‘The Origin and Role of MHC Class I-Associated Self-Peptides’’ 74
Response to Questions 75
I. Response to Question #1 75
II. Response to Question #2 75
References 76
Chapter 4: Functional Development of the T Cell Receptor for Antigen 78
I. Introduction 79
II. TCR Structure and Diversity 80
III. Thymic Self-Peptides Involved in T Cell Selection 82
IV. Synaptic and Nonsynaptic Interactions in the Thymus 86
V. miR-181a, A MicroRNA That Enhances T Cell Sensitivity and Promotes Tolerance 90
VI. The Selecting Ligand and the Purpose of Selection 93
VII. On the Role of Self-Peptides in the Activation of CD4+ Versus CD8+ T Cells 98
VIII. Conclusions 101
References 105
Section II: Thymic Requirements for T CellImmunity 114
Chapter 5 Transcriptional Regulation of Thymus Organogenesis and Thymic Epithelial Cell Differentiation 116
I. Introduction 117
II. Transcription Factors Controlling Organ Patterning and Initial Organogenesis 120
III. Patterning Events Lead to Induction of the Thymus-Specific Transcription Factor Foxn1 123
IV. NFkappab Pathway and Medullary Formation 126
V. Future Directions 127
References 128
Chapter 6: Early T Cell Differentiation:Lessons from T-Cell AcuteLymphoblastic Leukemia 134
I. Introduction 135
II. Oncogenic Transcription Factors 138
III. Signal Transduction Pathways 143
IV. Tumor Suppressors 153
V. Concluding Remarks 156
Acknowledgments 157
References 157
Section III: T Cell Immunity in the Periphery 170
Chapter 7: Lymphoid Tissue Inducer Cells and the Evolution of CD4 Dependent High-Affinity Antibody Responses 172
I. Introduction 173
II. LTi and the Development of Organized Lymphoid Structures 173
III. LTi Express Recently Evolved Tumor Necrosis Family Member Ligands 174
IV. High-Affinity Class Switched Antibodies Depend on LTa and LTbeta Induced Organization 176
V. AID-Dependent Class Switching Anticipated Affinity Maturation and CD4 Memory Antibody Responses 177
VI. The Genes for Organization Show Linkage with CD4 and AID 178
VII OX40L and CD30L are Expressed by LTi 180
VIII Lack of CD4 Memory in Mice Deficient in OX40 and CD30 180
IX CD30-Signals Evolved Before OX40 and the LTbetaR, and Share Functions in Both Organization and CD4 Memory 181
X Direct Evidence that LTI are Required for CD4 Memory 181
XI LTi and the Induction and Maintenance of Tolerance 182
XII Putative Origin of LTi and Summary 182
Acknowledgments 183
References 183
Chapter 8 Cellular and Molecular Requirements in Lymph Node and Peyer's Patch Development 190
I. Foreword 191
II. Historical Perspective: Lymphoid Tissue Development, 1836-1996 192
III. Tools and Technologies Transforming Analysis of Lymphoid Tissue Development 199
IV. 1996 Onward: Requirements for Lymph Node and Peyer's Patch Development 203
References 213
Chapter 9 T Follicular Helper Cells During Immunity and Tolerance 220
I. Introduction 221
II. T-Dependent Antibody Responses 222
III. Germinal Center-Derived Autoimmunity 225
IV. Germinal Center Tolerance 225
V. T Follicular Helper Cells 226
VI. Tfh Cells Mediate Selection of Germinal Center B Cells 227
VII. Breaks in Tfh Tolerance Result in Autoimmunity 231
VIII. Tolerizing Tfh Cells 233
IX. Concluding Remarks 249
References 250
Section IV: Preventing T Cell-Dependent Autoimmunity 262
Chapter 10: Thymic Selection and Lineage Commitment of CD4+Foxp3+ Regulatory T Lymphocytes 264
I. Introduction 265
II. The Treg-Repertoire 267
III. Thymic Selection of the Treg-Repertoire 269
IV. Thymic Commitment to the Treg-Lineage 275
V. Concluding Remarks 281
References 282
Chapter 11: Molecular Mechanisms of Regulatory T Cell Development and Suppressive Function 292
I. Tracing Thymic Treg Development with Foxp3 294
II. Acquisition of Foxp3 Expression by Peripheral CD4+ T Cells 297
III. Bottom-Up Approach to Analyzing Treg Cell Differentiation 299
IV. Cellular Targets of Treg Cells 306
V. Molecular Mechanisms of Treg Cell Suppression 312
VI. Concluding Remarks 319
References 319
Is Foxp3 the Master Regulatorof Regulatory T Cells? 328
References 330
Index 332