Umfang:
Online-Ressource (XXVII, 357 p. 70 illus., 3 illus. in color, online resource)
ISBN:
9780387097893
Serie:
Advances in Experimental Medicine and Biology 640
Inhalt:
Multichain Immune Recognition Receptors (MIRRs) represent a family of surface receptors expressed on different cells of the hematopoietic system and function to transduce signals leading to a variety of biologic responses. These receptors share common structural features including extracellular ligand-binding domains and intracellular signaling domains intriguingly carried on separate subunits. Another important feature that links members of the MIRRfamily is the presence of one or more copies of a cytoplasmic structural module termed the immunoreceptor tyrosine-based activation motif (ITAM). ITAMs consist of conserved sequences of amino acids that contain two appropriately spaced tyrosines (YxxL/Ix6-8YxxL/I, where x denotes non-conserved residues). Following receptor engagement, phosphorylation of ITAM tyrosine residues represents one of the earliest events in the signaling cascade. Although the MIRR-mediated ligand recognition and the MIRR-triggered downstream signaling cascades are believed to be among the best studied in biology in recent years, at present the spatial organization of the MIRRs, its reorganization in response to ligand binding as well as the molecular mechanisms underlying the initiation of MIRRsignaling remain to be elucidated. MIRR-mediated signal transduction plays an important role in both health and disease, making these receptors attractive targets for rational intervention in a variety of immune disorders. Thus, future therapeutic strategies depend on our detailed understanding of the molecular mechanisms underlying MIRRtriggering and subsequent transmembrane signal transduction. In addition, knowing these mechanisms would provide a new handle in dissecting the basic structural and functional aspects of the immune response. The central idea of this book is to show that the structural similarity of the MIRRs determines the general principles underlying MIRR-mediated transmembrane signaling mechanisms and also provides the basis for existing and future therapeutic strategies targeting MIRRs. The reviews assembled in this book detail the progress in defining and controlling the spatiotemporal organization of key events in immune cell activation. An improved understanding of MIRR-mediated signaling has numerous potential practical applications, from the rational design of drugs and vaccines to the engineering of cells for biotechnological purposes. Section I reviews the spatial organization and physiological function of MIRRfamily members such as Tcell receptor, B cell receptor, Fc receptors, natural killer cell receptors and the platelet collagen receptor glycoprotein VI. Section II focuses on current models of MIRRtriggering and highlights modern technologies available to visualize cell-cell interaction contacts such as immunological synapse and also to measure protein-protein interactions in space in real time. Potential therapeutic strategies targeting MIRR-mediated signaling are briefly reviewed in Section III. This book summarizes current knowledge in this field and illustrates how control of MIRR-triggered signaling could become a potential target for medical intervention, thus bridging basic and clinical immunology. Describing the molecular basis of MIRR-mediated transmembrane signaling, this volume addresses a broad audience ranging from biochemists and molecular and structural biologists to basic and clinical immunologists and pharmacologists.
Anmerkung:
Includes bibliographical references and index
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CONTENTS; 1. T-CELL RECEPTOR; 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 CDS Coreceptors; Other TCRs; Are All TCRs Equal, or Are Some TCRs More Equal Than Others?; Future Directions; 2. B-CELL RECEPTOR; Abstract; Introduction; Structure of the BCR; B-Cell Development; Molecular Aspects of Ligand-Induced BCR Signal Transduction; Membrane Compartmentalization of the BCR
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Balance between Positive and Negative Regulators of BCR SignalingLigand-Independent BCR-Induced Tonic Signaling; Conclusion; 3. FC RECEPTORS; 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; Abstract; Introduction; Inhibitory Receptors; Activating Receptors; Conclusions; 5. PLATELET GLYCOPROTEIN VI; Abstract; Introduction; Structure of GPVI; Interaction of GPVI with Collagen
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GPVI-Mediated Signal TransductionPhysiological Function of GPVI; Summary and Perspectives; 6. CLUSTERING MODELS; Abstract; Introduction; Homoclustering; Heteroclustering; Pseudodimer Model; Homo- and Heteroclustering and Lipid Rafts; The PreTCR and PreBCR; 7. SEGREGATION MODELS; Abstract; Introduction; Lipid Rafts; Segregation by Raft Clustering; Kinetic-Segregation Model; Immune Synapse and Microclusters; 8. KINETIC PROOFREADING MODEL; Abstract; Introduction; Kinetic Proofreading Illustrated through FCERI Signaling; The Extent of Kinetic Proofreading in FCERI Signaling
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Some Responses May Escape Kinetic ProofreadingMcKeithan's Mathematical Formulation; T-Cell Activation and the Competition between Kinetic Proofreading and Serial Engagement; Concluding Remarks; 9. SERIAL TRIGGERING MODEL; 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; Abstract; Introduction; Evidence in Favour of Conformational Changes in MIRRs; Consequences for Ligand Recognition
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Model for Transmission of Conformational ChangesConclusions; 11. PERMISSIVE GEOMETRY MODEL; 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 HOMOOLIGOMERIZATION (SCHOOL) MODEL; Abstract; Introduction; Central Hypothesis; SCHOOL Model of MIRR Signaling; Conclusions; 13. VISUALIZATION OF CELL-CELL INTERACTION CONTACTS-SYNAPSES AND KINAPSES; Abstract; Introduction; New Model for Sustained Signaling through the Synapse
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In Vivo Functions of Synapse and Kinapse
Weitere Ausg.:
ISBN 9780387097886
Weitere Ausg.:
Erscheint auch als Druck-Ausgabe Cervós-Navarro, Jorge Pathologie des Nervensystems ; 1: Durchblutungsstörungen und Gefäßerkrankungen des Zentralnervensystems von J. Cervós-Navarro ; H. Schneider Berlin : Springer, 1980 ISBN 0387097880
Weitere Ausg.:
ISBN 3540097880
Sprache:
Englisch
Fachgebiete:
Medizin
DOI:
10.1007/978-0-387-09789-3
