Beschreibung:
This book intends to assemble reviews on the progress in defining and controlling the spatiotemporal organization of key events in immune cell activation. Improved understanding of MIRR-mediated signaling has a number of potential practical applications, from the rational design of drugs and vaccines to the engineering of cells for biotechnological purposes. In Section 1, spatial organization and physiological function of the MIRR family members such as T cell receptor (TCR), B cell receptor (BCR), Fc receptors, natural killer (NK) cell receptors, and platelet glycoprotein VI (GPVI) will be reviewed. Section 2 will focus on current models of MIRR-triggering and highlight modern technologies to visualize cell-cell interaction contacts such as immunological synapse and to measure protein-protein interactions in space in real time. Potential therapeutic strategies targeting the MIRR-mediated transmembrane signal transduction will be shortly reviewed in Section 3. This book will summarize our current knowledge in this field and illustrate how control of the MIRR-triggered signaling could become a potential target of medical intervention, thus bridging basic and clinical immunology.
"This book intends to assemble reviews on the progress in defining and controlling the spatiotemporal organization of key events in immune cell activation. Improved understanding of MIRR-mediated signaling has a number of potential practical applications, from the rational design of drugs and vaccines to the engineering of cells for biotechnological purposes. In Section 1, spatial organization and physiological function of the MIRR family members such as T cell receptor (TCR), B cell receptor (BCR), Fc receptors, natural killer (NK) cell receptors, and platelet glycoprotein VI (GPVI) will be reviewed. Section 2 will focus on current models of MIRR-triggering and highlight modern technologies to visualize cell-cell interaction contacts such as immunological synapse and to measure protein-protein interactions in space in real time. Potential therapeutic strategies targeting the MIRR-mediated transmembrane signal transduction will be shortly reviewed in Section 3. This book will summarize our current knowledge in this field and illustrate how control of the MIRR-triggered signaling could become a potential target of medical intervention, thus bridging basic and clinical immunology."
Foreword; William Paul
Preface; Alexander B. Sigalov
Section I. MIRRs: Structure and Physiological Function
1. T-Cell Receptor; Jose M. Rojo, Raquel Bello and Pilar Portolés
Abstract
Introduction
Minimal Components and Stoichiometry of the TCR/CD3 Complex
TCR Clusters on the Cell Surface
Topology of Chain Interactions within TCR/CD3 Complexes
Interactions between the TCR and Antigen-Role of CD4 and CD8 Coreceptors
Other TCRs
Are All TCRs Equal, or Are Some TCRs More Equal Than Others?
Future Directions
2. B-Cell Receptor; Randall J. Brezski and John G. Monroe
Abstract
Introduction
Structure of the BCR
B-Cell Development
Molecular Aspects of Ligand-Induced BCR Signal Transduction
Membrane Compartmentalization of the BCR
Balance between Positive and Negative Regulators of BCR Signaling
Ligand-Independent BCR-Induced Tonic Signaling
Conclusion
3. Fc Receptors; Maree S. Powell and P. Mark Hogarth
Abstract
Introduction
Human receptors for immunoglobulin
Interaction between Fc receptor and immunoglobulin
Spatial organization of FcRs
Physiological function of Fc receptors
Concluding comments
4. Natural Killer Cell Receptors; Roberto Biassoni
Abstract
Introduction
Inhibitory Receptors
Activating Receptors
Conclusions
5. Platelet Glycoprotein VI; Stephanie M. Jung and Masaaki Moroi
Abstract
Introduction
Structure of GPVI
Interaction of GPVI with collagen
GPVI-mediated signal transduction
Physiological Function of GPVI
Summary and perspectives
Section II. MIRR Signaling: Possible Mechanisms and the Techniques to Study and Visualize
6. Clustering Models; Wolfgang W.A. Schamel and Michael Reth
Abstract
Introduction
Homoclustering
Heteroclustering
Pseudodimer Model
Homo- and Heteroclustering and Lipid Rafts
The PreTCR and PreBCR
7. Segregation Models; Elaine P. Dopfer, Mahima Swamy, Gabrielle M. Siegers, Eszter Molnar, Jianying Yang and Wolfgang W.A. Schamel
Abstract
Introduction
Lipid Rafts
Segregation by Raft Clustering
Kinetic-Segregation Model
Immune Synapse and Microclusters
8. Kinetic Proofreading Model; Byron Goldstein, Daniel Coombs, James R. Faeder and William S. Hlavacek
Abstract
Introduction
Kinetic proofreading illustrated through FceRI signaling
The extent of kinetic proofreading in FceRI signaling
Some responses may escape kinetic proofreading
McKeithan's mathematical formulation
T-Cell activation and the competition between kinetic proofreading and serial engagement
Concluding remarks
9. Serial Triggering Model; Jacob Rachmilewitz
Abstract
T-Cell Receptor Signaling Cascade
Serial Triggering Model
Flexible and hierarchical T-Cell Activation Thresholds
Temporal Summation as a mechanism for Signal Integration
Summary
10. Conformational Model; Ruth M. Risueño, Angel R. Ortiz and Balbino Alarcón
Abstract
Introduction
Evidence in Favour of Conformational Changes in MIRRs
Consequences for Ligand Recognition
Model for Transmission of Conformational Changes
Conclusions
11. Permissive Geometry Model; Susana Minguet and Wolfgang W.A. Schamel
Abstract
Introduction
The clustering model of TCR triggering
Oligomeric MIRRs
Conformational changes within the MIRRs
Permissive geometry model
Agonist/self-peptide-MHC heterodimers
12. Signaling Chain Homoligomerization (Schol) Model; Alexander B. Sigalov
Abstract
Introduction
Central Hypothesis
Schol Model of MIRR Signaling
Conclusions
13. Visualization of Cell-Cell Interaction: Contacts-Synapses and Kinapses; Michael L. Dustin
Abstract
Introduction
New model for sustained signaling through the synapse
In vivo functions of synapse and kinapse
In vivo Analysis of CD4+ T-Cell Priming and Tolerance Induction
In vivo analysis of CD8+ T-Cell priming and tolerance induction
Priming vs. tolerance
Dynamics of CD4+ T-Cell Help for CD8+ T-Cell responses
Effector sites
Summary
14. Visualization of Protein Interactions in Living Cells; Tomasz Zal
Abstract
Introduction
FRET
Bimolecular Fluorescence complementation
Fluorescence correlation techniques
Fluorescent labeling of proteins in living cells
Quantitative FRET imaging
Using FRET to analyze receptor (re)arrangements
Imaging TCR-coreceptor interactions in the immunological synapse
Affinity versus random collisions: acceptor titration FRET
Mathematical model of FRET for simultaneous complex formation and random collisions
Conclusion
Section III. MIRR Signaling and Therapy of Immune Disorders
15. Immunogenicity in Peptide-Immunotherapy: From Self/Nonself to Similar/Dissimilar Sequences; Darja Kanduc
Abstract
Introduction
The Question: What Renders a peptide immunogenic?
From a Historical Point of View-The Immune Response and Self/Nonself Sequences
From a Logical Point of View-The Immune Response and Similar/Dissimilar Sequences
Browsing through Literature: Similarity Level of Identified Epitopes
Concluding Remarks
16. Therapeutic Aplication of Transmembrane T and Natural Killer Cell Receptor Peptides; Nicholas Manolios, Marina Ali, Michael Amon and Veronika Bender
Abstract
Introduction
Therapeutic Application
Biophysical Attributes of CP
Biological Features of CP
Peptide Bioavailability
Effects of CP Conjugation
Conclusion
17. Fc Receptor Targeting in the Treatment of Allergy, Autoimmune Diseases and Cancer; Akira Nakamura, Tomohiro Kubo and Toshiyuki Takai
Abstract
Introduction
FcR function
FcR-targeting therapy
Conclusion
18. Therapeutic Blockade of T-Cell Antigen Receptor Signal Transduction and Co-stimulation in Autoimmune Disease; Joseph R. Podojil, Danielle M. Turley and Stephen D. Miller
Abstract
Introduction
T-Cell activation: target for treatment of disease
Coupled-cell tolerance: antigen-specific induction of tolerance to a self-antigen
Immune synapse: activation of the TCR in lipid rafts
NFAT: Regulation of T-Cell activation and anergy
NFAT inhibitors: putative therapeutics
LAT: an Alternative component of TCR signaling
Conclusions
19. MHC and MHC-Like Molecules: Structural Perspectives on the Design of Molecular Vaccines; Vasso Apostolopoulos, Eliada Lazoura and Minmin Yu
Abstract
Introduction
Stimulation of CD8 T Cells
MHC class I molecules
Noncanonical features of peptide-binding to MHC class I molecules
Stimulation of CD4 T Cells
MHC Class II Molecules
MHC class III molecules
MHC gene mutations
Nonclassical MHC Class I Molecules
Nonclassical MHC Class II Molecules
MHC-Peptide Interaction with the TCR
MHC Class I-like Molecules
Future Prospects
20. SCHOOL Model and New Targeting Strategies; Alexander B. Sigalov
Abstract
Introduction
Long-Standing Mystery of MIRR Triggering and Transmembrane Signaling
SCHOOL Model of MIRR Triggering and Signaling: Basic Concept, Major Driving Forces, Restraints and Advantages
SCHOOL Model: New Intervention Points for MIRR-Mediated Immune Disorders
Conclusions
21. Immune Receptor Signaling, Aging and Autoimmunity; Anis Larbi, Tamas Fülöp and Graham Pawelec
Abstract
Introduction
Immunosenescence
Receptor Signaling in Immunosenescence
The Role of Membrane Rafts in TCR Signaling: The Aging Rafts
Heterogeneity in Membrane Rafts and T-cell Subsets
MIRR Signaling and Autoimmunity
Therapeutic Strategies Targeting the MIRR Signaling
Conclusion
22. Viral Pathogenesis, Modulation of Immune Receptor Signaling and Treatment; Walter M. Kim and Alexander B. Sigalov
Abstract
Introduction
Viruses: Classification and Pathogenesis
Viral Entry and Membrane Targeting
Viral Replication
Translation of Redundant Viral Strategies into Disease Care
Conclusions and Perspectives