Interleukin 2 focuses on interleukin 2 (IL-2) and its impact on immunology. Topics covered include IL-2's mechanism of action, the structure of the IL-2 receptor, the characteristics of natural and recombinant human IL-2, regulation of IL-2 production by the T cell antigen receptor, how IL-2 binding induces the transcription of a novel set of genes, and the pathological roles of IL-2 receptor inducers in adult T cell leukemia. This book is comprised of 12 chapters and begins with a historical overview of IL-2, from the discovery of soluble mitogenic factors in culture media of stimulated lymphocytes to the discovery of IL-2 as the molecule responsible for stimulating T cell proliferation. The physicochemical and biological properties of purified recombinant IL-2 are then described, paying particular attention to natural IL-2 derived from human peripheral blood leukocytes. The chapters that follow discuss the different techniques used to gain insight into the functionally important regions of IL-2, the role of the T cell antigen receptor in regulating the production of IL-2, and the structure of the human high-affinity IL-2 receptor. The book also describes transmembrane signaling by IL-2, IL-2-inducible gene expression in T lymphocytes, abnormal IL-2 receptor expression in adult T cell leukemia, the use of IL-2 receptors in immunosuppressive therapy, and the use of IL-2 as a pharmacologic reagent. This book will be of interest to students and researchers in immunology and biochemistry.
Inhalt
Contributors
Preface
Foreword
1. Interleukin 2: A 10-Year Perspective
I. Introduction
II. Interleukin 2
III. The IL-2 Receptor
IV. IL-2 Receptor Structure
V. Functional Consequences of the IL-2 Receptor Bimolecular Structure
VI. a Chains Are Responsible for Stimulating Cell Cycle Progression
VII. The Regulation of IL-2 Receptor Expression
VIII. The IL-2 Receptor Regulation of T Cell Growth
IX. IL-2 Stimulates T Cell G1 Progression and c-myb Expression
X. Conclusions
References
2. Characteristics of Natural and Recombinant Human Interleukin 2
I. Introduction
II. Natural IL-2 Derived from Human PBL
III. Recombinant IL-2 Derived from E. coli
IV. Comparison of Biological Activities for Natural and Recombinant IL-2
V. Summary and Conclusions
References
3. Interleukin 2: Approaches to Structure Determination
I. Introduction
II. Preliminary Data
III. Species Homology
IV. Antibodies as Structure Probes
V. Recombinant DNA-Derived Proteins and Site-Directed Mutagenesis
VI. Peptide Synthesis
VII. Molecular Modeling and Graphics
VIII. Conclusion
References
4. Regulation of Interleukin 2 Production by the T Cell Antigen Receptor
I. Introduction
II. The T3/Ti Complex: Obligate Coexpression of T3 with Ti
III. Jurkat as a Model for the Study of T3/Ti-Mediated Activation
IV. The Role of Increases in the Concentration of Cytoplasmic Free Ca2+ in T3/Ti-Mediated Signaling
V. T3/Ti-Mediated Turnover of Polyphosphoinositides
VI. T3/Ti Activates Protein Kinase C
VII. Cholera Toxin Inhibits T3/Ti-Mediated Polyphosphoinositide Turnover
VIII. Induction of IL-2 Transcripts Requires Sustained T3/Ti-Ligand Interactions
IX. Summary and Future Directions
References
5. New Perspectives on the Structure of the Human High-Affinity Interleukin 2 Receptor
I. Introduction
II. Characterization of the Human IL-2 Receptor (Tac Antigen)
III. High- and Low-Affinity Forms of the IL-2 Receptor
IV. Expression of the Tac cDNA in Eukaryotic Cells
V. Structural Analysis of the High-Affinity IL-2 Receptor
References
6. Transmembrane Signaling by Interleukin 2
I. Introduction
II. Transmembrane Events in IL-2-Induced Proliferation
III. Delayed Events
IV. Oncogene Expression
V. Discussion
References
7. Mechanisms of Interleukin 2 Action: IL-2-Inducible Gene Expression in T Lymphocytes
I. Introduction
II. Early Molecular Events Associated with the Interaction of IL-2 and IL-2 Receptor: Potential Involvement of Protein Kinase C and Calcium
III. Rationale for Investigating the Expression of Protooncogenes and Other Genes in IL-2-Stimulated T Lymphocytes
IV. IL-2-Inducible Expression of Genes in Activated T Lymphocytes
V. Some Possible Explanations for the Patterns of Gene Expression Induced by IL-2, Phorbol Esters, and Mitogenic Lectins in Activated T Lymphocytes
VI. Mechanisms of IL-2-Mediated Gene Expression
VII. IL-2-Mediated Signal Transduction: Speculations and Future Directions
References
8. Interleukin 2 Binding Induces Transcription of a Novel Set of Genes: Implications for T Lymphocyte Population Dynamics
I. Introduction
II. Modes of IL-2 Induction
III. Mechanics of IL-2 Action
IV. Measures of IL-2 Responsiveness
V Significance of Positive IL-2 Receptor Regulation
VI. Conclusion
References
9. Abnormal Interleukin 2 Receptor Expression in Adult T Cell Leukemia
I. Introduction
II. Development of Anti-Tac Monoclonal Antibody
III. Identification of Anti-Tac Antibody as an Anti-IL-2 Receptor Antibody
IV. Characterization of IL-2 Receptor
V. IL-2R Expression in B Cells
VI. IL-2R Expression in ATL
VII. HTLV-I Infection and IL-2R Expression
VIII. Possible Role of IL-2 Receptor in the Leukemogenesis of ATL
IX. IL-2R Expression in T Cell Chronic Lymphocytic Leukemia
X. Summary
References
10. Interleukin 2 Receptor Inducers: Pathological Roles in Adult T Cell Leukemia
I. Introduction
II. Studies of IL-2R and ATL
III. Properties of Human IL-2R Protein
IV. Cloning of IL-2R Gene
V. Humoral Control of IL-2R Expression
VI. Abnormal Regulation of IL-2R Expression in ATL
VII. ADF Inducing IL-2R Expression
VIII. IL-2-Dependent and -Independent ATL: Stepwise Progression Model
IX. Possible Roles of IL-2R Dysregulation in ATL
X. Conclusion
References
11. Interleukin 2 Receptor-Directed Immunosuppressive Therapy
I. Introduction
II. Effect of M7/20 Treatment on Murine Cardiac Allografts
III. Effect of M7/20 Treatment of Murine Skin Allografts
IV. Effect of M7/20 and Anti-L3T4 Antibodies on Delayed-Type Hypersensitivity (DTH): The Role of Complement and Epitope
V. Effect of M7/20 Anti-IL-2R Antibody on Murine Autoimmunity: Diabetes Mellitus and Systemic Lupus Erythematosus Models
VI. Effect of ART18 Anti-IL-2R Antibody Treatment on Rat Cardiac Allografts
VII. Synergistic Effect of Anti-IL-2R mAb and Cyclosporin (CsA) Treatment
VIII. Effect of Anti-IL-2R on Graft Infiltration
IX. Effect of ART18 Treatment on Host Alloreactivity
X. Effect of ART18 Therapy on Pancreatic Islet Allografts
XI. Anti-IL-2R mAb Treatment of Subhuman and Human Pri…