Molecular Mechanisms of Immunological Self-Recognition

Molecular Mechanisms of Immunological Self-Recognition covers the understanding of immunological self-recognition. The introductory chapter of the book summarizes the dawn of the insight into immunological tolerance, and provides an overview of research on the underlying mechanisms. The book addresses the developments in the molecular mechanisms of B and T cell tolerance and describes the failure of tolerance in autoimmunity. The text concludes by furnishing orienting perspectives and highlighting new information presented. The novel findings characterized as impressive advances pertain to the areas of B cell development and the generation of molecular diversity; V gene usage, especially from transgenes, in positive and negative thymic selection; the handling of positive and negative signals by T and B cells; anergy in postthymic T cells; the design of peptide-based therapy for autoimmune diseases; and the design of therapy with the aid of monoclonal antibodies. Immunologists will find the text useful.

PrefacePart 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 ReferencesPart 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? ReferencesPart 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 ReferencesPart 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 aß 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-Superantigen