Immunological Synapse (eBook)

183767_1_En_BookFrontmatter_OnlinePDF 1
183767_1_En_1_Chapter_OnlinePDF 16
Insights into Function of the Immunological Synapse from Studies with Supported Planar Bilayers 16
Introduction: Role of Receptor-Ligand Interaction in Immunity 17
Degrees of Freedom in Immune Cell Activation 18
Planar Bilayers and the Proof of MHC-Peptide Complexes 19
Determination of Two-Dimensional Affinity 21
Kinetic Rates of Interactions in Contact Area 22
Tandem Low-Affinity Interactions Have Additional Limitations 24
Segregation of Adhesion Molecules by Size 24
Formation of the Immunological Synapse 25
Microclusters Drive Activation 26
Modes of T-Cell Signal Integration 27
B Lymphocytes Acquire Antigen by Force 28
The F-Actin Machine Behind the Synapse 29
What Is the Function of the Immunological Synapse? 31
Conclusions 33
References 33
183767_1_En_2_Chapter_OnlinePDF 40
Immunological Synapses Within Context: Patterns of Cell-Cell Communication and Their Application in T-T Interactio 40
Introduction 41
The Emergent Prototypical Immunological Synapse Dynamics 42
Functional Patterns of Cell-Cell Communication 45
Dynamic Cellular Assembly and Disassembly 45
Defined but Flexible Polarity 47
Close Membrane-Membrane Juxtaposition with a Synaptic Cleft 47
Aggregation and Segregation of Transmembrane Receptors and Lipids 48
Four Fundamental Immunological Synapse Patterns Are Observed in the Interactions of Activating T Cells with One Another 49
Signaling Implication of T-T contacts for IL-2 Receptor Structure and Function 53
Additional Roles of T-T Synaptic Contact 56
Physiological Circumstances of T-Cell Cluster Formation and Its Role in Secondary Responses 56
``Quorum Sensing´´ by the Immune System for Activation and Differentiation of the Effectors 57
Polarization of Helper T-Cell Differentiation via Synaptic Cytokine Sharing 57
T-T Interactions during the Cessation of the Immune Response: The Facilitation of Fas/TNF Interactions Leading to Apopt 58
Treg Exclusion in T-T Contacts 58
Creating System-Wide Decisions Through Collective and Spatiotemporal Information Sharing 59
Cell-Based Vectorial Spreading of Information 60
Selection of a System of Appropriate Cell Types 60
A Very Steep Gradient of Cues at Each Encounter Point 60
Repeated Selection for Specificity and Mutual Enhancement 60
Concluding Remarks 61
References 61
183767_1_En_3_Chapter_OnlinePDF 66
Molecular and Cellular Dynamics at the Early Stages of Antigen Encounter: The B-Cell Immunological Synapse 66
Introduction 67
Molecular Dynamics of B-Cell Antigen Recognition and IS Formation 67
A Two-Phase Response Leads to B-Cell Synapse Formation 67
Microsignalosomes as the Basic Unit of Signalling in B Cells 69
The Importance of the Context 70
Antigen Presenting Cells 71
Cellular Dynamics at the Onset of the B-Cell Response In Vivo 71
The Naïve B-Cell Migration Pattern: Searching for Antigen 71
Early Steps in Antigen Recognition and Activation of Naïve B Cells 72
Tracking Antigen Recognition In Vivo 73
In Vivo B-Cell Dynamics 74
B-Cell IS In Vivo 75
Concluding Remarks 75
References 76
183767_1_En_4_Chapter_OnlinePDF 78
Inhibitory and Regulatory Immune Synapses 78
Introduction 79
Definition of Inhibitory Immune Synapses 79
Formation of Inhibitory Synapses 80
Balancing Synapses with Kinapses and Kinetic Proofreading at the Cellular Level 84
Unzipping the Synapse 85
Regulatory Synapses 85
The Regulatory NK-Cell Synapse 86
Triggering Cytokine Secretion Versus Cytolysis 86
References 88
183767_1_En_5_Chapter_OnlinePDF 95
The Immunological Synapse, TCR Microclusters, and T Cell Activation 95
Introduction 96
The Immunological Synapse 97
Discovery of the Immunological Synapse 97
Architecture of the Immunological Synapse 97
TCR Microclusters and the Immunological Synapse 98
Discovery of TCR Microclusters 98
Dynamics of TCR Microcluster Formation 99
TCR Microcluster as a Signalosome for T cell Activation 101
Microcluster Composition 101
Evidence of Microclusters as Signalosome 102
Lipid Raft Microdomains and TCR Microclusters 104
c-SMAC Function 105
Dual Functions in TCR Signaling 105
Cell Polarity and the c-SMAC 106
Heterogeneity of the Immunological Synapse and the c-SMAC 107
Costimulation Regulation by TCR Microclusters and the c-SMAC 108
Costimulation and TCR Microclusters 108
Functional Subregions Within the c-SMAC 108
T cell Activation Models and the TCR Microcluster Model 111
Concluding Remarks 114
References 114
183767_1_En_6_Chapter_OnlinePDF 122
Signaling Amplification at the Immunological Synapse 122
Introduction 123
CD28 and Lipid Rafts 123
Chemokines and Their Receptors 126
Coinhibitory Receptors 129
Conclusions 130
References 131
183767_1_En_7_Chapter_OnlinePDF 136
Multiple Microclusters: Diverse Compartments Within the Immune Synapse 136
Challenges in Antigen Recognition 137
T Cell Migration and Synapsis 138
Models of Antigen Recognition 140
The Structure of the Immune Synapse 141
Cytoskeletal Rearrangements Associated with Contact Formation 142
The Regulation of Contact Formation and Persistence 144
Signal Initiation within the Earliest Contact 146
The TCR Microcluster 146
Rapid Signal Initiation in TCR Microclusters 147
TCR Microclusters as Topological Confinement Domains 148
TCR Microclusters and the Kinetic Segregation Hypothesis 148
The SLP-76 Microcluster 148
The Stabilization and Movement of SLP-76 Microclusters 149
The SLP-76 Microcluster as an Analog-to-Digital Converter 150
The Segregation of SLP-76 Microclusters from the TCR 150
SLP-76 Microclusters Are Primarily Organized by Protein-Protein Scaffolds 151
Integrin Microclusters 152
Integrins Impact the Movement of SLP-76 Microclusters 153
Adaptors Linking Integrins to SLP-76 Microclusters 153
Accessory Microclusters 154
CD2 Microclusters and the Inner Adhesion Ring 154
CD28 Microclusters Promote Costimulation and Stable Adhesion 155
The Bi-Functional cSMAC 156
Microcluster Centralization and Termination 156
Signal Amplification in the cSMAC 157
Concluding Thoughts 157
Revisiting the SMACs: Toward Terms with Functional Definitions 157
A Cell Biological Basis for Model-Independent Microclusters? 159
References 161
183767_1_En_8_Chapter_OnlinePDF 168
A Conformation-Induced Oligomerization Model for B cell Receptor Microclustering and Signaling 168
Introduction 169
How B Cells See Antigens In Vivo 171
Imaging B cell Interactions with Antigen In Vitro: Defining the B cell Immune Synapse 172
Models for the Mechanisms by Which BCRs Cluster 174
Insights into the Mechanism of BCR Microcluster Formation from Single Molecule Imaging 175
Is There Evidence for Conformation-Induced Oligomerization Predicted by the Model? 177
Implications of the ``Conformation-Induced Oligomerization´´ Model for B cell Biology 177
The Unsolved Problem of Transducing Conformational Changes in the BCR Ectodomains to the Cytoplasmic Domains 179
Conclusions 180
References 180
183767_1_En_9_Chapter_OnlinePDF 183
Co-Receptors and Recognition of Self at the Immunological Synapse 183
Introduction 184
Co-Receptors in the Immunological Synapse 184
MHC Recognition by Co-Receptors 184
Co-Receptor Recruitment to the Immunological Synapse 185
Co-Receptor Interaction with NonCognate MHC Class I in Antigen Recognition 186
NonStimulatory Peptides Aid MHC Class I-Restricted Antigen Recognition by T Cells 186
The FRET Response Between CD8 and TCR-CD3, and What It Tells Us About the Role of Endogenous Peptides in T-Cell Activati 190
Differing Co-Receptor Roles in Recognition of Endogenous MHC Class I- and II-Peptide? 192
NonStimulatory Peptides Aid MHC Class II-Restricted Antigen Recognition by T Cells 192
Predictions and Tests of the Pseudodimer and Pre-Concentration Models 193
Different Roles for CD4 and CD8 Co-Receptors in Endogenous Peptide Recognition 195
Does Co-Receptor-MHC Interaction Precede or Follow TCR Recognition of pMHC? 196
Adhesion and TCR Cross-Linking in T-Cell Activation 196
Concluding Remarks 197
References 197
183767_1_En_10_Chapter_OnlinePDF 202
Vesicle Traffic to the Immunological Synapse: A Multifunctional Process Targeted by Lymphotropic Viruses 202
Introduction 1. Introduction 203
Polarized Vesicle Traffic to the Immunological Synapse2. Polarized vesicle traffic to the immunological synapse 204
Polarization of the Microtubule Cytoskeleton2.1. Polarization of the microtubule cytoskeleton 204
Polarization of the Golgi Apparatus and the Secretory Vesicle Traffic2.2. Polarization of the Golgi apparatus and the secretor 204
Polarization of Cytotoxic Granules2.3. Polarization of cytotoxic granules 206
Polarization of Endosomal Compartments2.4. Polarization of endosomal compartments 206
Polarization of Vesicular Compartments Carrying Signal Transduction Proteins 207
The Immunological Synapse, an Active Zone for Vesicle Docking and Fusion2.6. The immunological synapse, an active zone for ves 208
Infection by Lymphotropic Viruses Modulates Intracellular Molecular Trafficking to the Immunological Synapse and T-Cell Signa 208
HIV-13.1. HIV-1 209
HTLV-13.2. HTLV-1 211
Herpesvirus saimiri3.3. Herpesvirus saimiri 212
Conclusion and Remaining Questions4. Conclusion and remaining questions 213
References 214
183767_1_En_11_Chapter_OnlinePDF 219
Plasticity of Immunological Synapses 219
Introduction 220
Heterogeneity of Immunological Synapses 221
Antigen-Independent Initial Cell-Cell Contact 221
Antigen-Driven Cell-Cell Contact Stabilization 222
Molecular Segregation and Signal Transduction 222
Heterogeneous IS Support T Cell Biological Functions 223
Dynamics of IS Assembly and Signal Integration: Central Role of the Actin Cytoskeleton 224
Actin Regulatory Proteins: Integrating MultiFactorial Stimulation into Adapted Actin Remodeling in Time and Space 227
Immunological Synapses Are Adaptable Structures 229
On the ``Raison d´être´´ of Immunological Synapse Plasticity 232
References 233
183767_1_En_12_Chapter_OnlinePDF 239
APC, T Cells, and the Immune Synapse 239
Introduction 240
Generation of T cell Precursors in the Bone Marrow: The Hematopoietic Synapse 240
Generation of T cells in the Thymus: Thymic Synapses 241
Antigen Presentation in the Lymph Node Is Mainly Done by Dendritic Cells 244
B Cells as APC 247
T Cells Helping B Cells to Function 249
IS and APC-Mediated Induction of Treg: Focus on Co-stimulatory Molecules 250
Concluding Remarks 251
References 254
183767_1_En_BookBackmatter_OnlinePDF 260
: Index 260