Isolation Characterization, and Utilization of T Lymphocyte Clones

Isolation, Characterization, and Utilization of T Lymphocyte Clones is a summary of information regarding T lymphocyte clones, including their usefulness. Organized into nine parts, the book begins with discussions on the soluble factors that can influence the growth of cloned T cells and the utilization of T cell hybridomas for analysis of T cell functions, emphasizing the biochemical and functional properties of helper and suppressor factors. The book then looks into the analysis of T cell clones and hybridomas using techniques of somatic cell genetics. The clonal analysis by limiting dilution, the characteristics of murine T cell clones reactive with alloantigens and soluble antigens, and the human T cell clones are described as well. This volume is valuable to those interested in the field of cloning of immunocompetent T cells.

ContributorsPreface1 Introduction and Historical Overview Text References2 Differentiation within the Immune System: The Importance of Cloning I. Comparison with the Nervous System II. Cloning Methods III. Questions of the Day ReferencesI. IL-1 (Lymphocyte Activating Factor) and IL-2 (T Cell Growth Factor) 3 Biochemical Characterization of Interleukin-2 (T Cell Growth Factor) I. IL-2 Microassay II. Purification of Human and Murine IL-2 III. Temperature, Chemical, and Enzymatic Treatments of IL-2 IV. Improved Cellular Sources for IL-2 Production and Characterization V. Polyacrylamide Gel Electrophoresis of IL-2 VI. Molecular Prospects for the Future VII. Conclusions References 4 Production and Assay of Interleukin-1 (IL-1) I. Production of IL-1 II. IL-1 Assay III. Conclusions References 5 Production and Properties of Human IL-2 I. Introduction II. Culture Conditions for Generation of Human IL-2 III. Testing of Culture Supernatant for IL-2 Content IV. Removal of PHA from IL-2-Containing Culture Supernatants V. Long-Term Growth of Cytotoxic T Lymphocytes in IL-2 VI. Use of IL-2-Containing Preparations for Activation of Cytolytic Lymphocytes: IL-2 Providing the Proliferative Stimulus Necessary for Allogeneic IVS VII. Conclusions References 6 Signal Requirement for T Lymphocyte Activation I. T Lymphocyte Propagation II. T Lymphocyte Activation ReferencesII. T Cell Hybridomas and Their Products 7 An Overview I. A Catalog II. Problems III. Lessons IV. Conclusions References 8 Factors, Receptors, and Their Ligands: Studies with H-2 Restricted Helper Hybridoma Clones I. la-Associated Antigen Complex II. Isolation of T Hybridomas III. Characterization of the Hybridoma Clones IV. Analysis of the Altered Self-Dual Recognition Problem V. Isolation of Helper Factors References 9 Properties of Antigen-Specific H-2 Restricted T Cell Hybridomas I. Factor Production by T Cell Hybridomas II. Use of T Cell Hybridomas to Examine Properties of the T Cell Receptor III. T Cell Hybridomas Do Not Express Unexpected H-2 Spécificités IV. Karyotypic Analysis of T Cell Hybridomas References 10 Studies on an Antigen-Specific Suppressor Factor Produced by a T Hybrid Line I. Derivation and Specificity of the Al Supressor Line II B Cells as the Targets for Al Factor III. Genetic Control of Suppression IV. Interaction between Suppressor Factor and Monoclonal Antibodies in Regulation of the Immune Response V. Conclusion References 11 Characterization of Antigen-Specific Suppressor Factors from T Cell Hybridomas I. Experimental Systems Used to Identify Suppressor T Cells and Their Products II. Characterization of GAT- and GT-Specific TsF III. Comparison of GAT-TsF and GT-TsF to Other Suppressor T Cell Factors References 12 Suppression of Antibody Responses by a T Cell Hybridoma-Derived Haplotype-Specific Suppressor Factor I. Properties of TsF-H II. Mechanism of Action of TsF-H III. Conclusions References 13 Soluble Immune Response Suppressor (SIRS) Derived from T Cell Hybridomas I. Characteristics of SIRS II. Speculations ReferencesIII. The Somatic Cell Genetic Analysis of Cytolytic T Lymphocyte Functions 14 An Overview I. CTL Lines II. Mutants III. Somatic Cell Hybrids IV. Outlook References 15 Karyotype Evolution of Cytolytic T Cell Lines I. Karyotype Analysis of Functional T Cell Lines II. Discussion References 16 Growth Regulation of Cytolytic T Cell Lines by Interleukin-2 I. Mechanisms of Action of Growth Factors II. Mechanisms of Action of TCGF on a Cloned CTL Line References 17 Correlation between Cytolytic Activity, Growth Factor Dependence, and Lectin Resistance in Cytolytic T Cell Hybrids I. Introduction II. Origin of CTL Hybrids III. CTL Activity, VV Resistance, and CS Dependence of Hybrids IV. Selection of C S - Variants from Cloned C S + Cytolytic Hybrids V. Conclusions References IV. Clonal Analysis by Limiting Dilution 18 An Overview I. Theory of Limiting Dilution II. Experimental Conditions Required for Limiting Dilution Analysis of CTL-P Frequencies III. The CTL-P Frequency Problem References 19 Clonal Analysis of Helper and Cytolytic T Cells: Multiple, Independently RegulatedPrecursor Sets at Frequencies Suggesting a Limited Repertoire I. The Assay II. Multiple Populations of T Precursor Cells III. Independent Regulation of Each Precursor Population IV. Lyt-Phenotypic Differences between T Precursor Populations V. Conclusions References 20 Frequency, Regulation, and H-2 Epitope Specificity of Alloreactive and H-2 RestrictedCTL Clones I. Topographic Arrangement of Alloantigenic Determinants on the H-2Kk Molecule II. Distinct CTL Subpopulations with Different Precursor Frequencies Detected by Limiting Dilution Analysis III. Target Inhibition by mc Anti-H-2 of CTL Clones Generated in the Limiting Dilution System IV. Target Inhibition of H-2Kk-Restricted, TNP-Specific CTL Clones Conclusions References 21 Production of Lymphokines by Murine T Cells Grown in Limiting Dilution and Long-Term Cultures I. Introduction II. Analysis of Lymphokine Release in Limiting Dilution Microcultures III. Analysis of Lymphokine Production from Long-Term T Cell Clones and Lines IV. Conclusions ReferencesV. Murine T Cell Clones Reactive with Alloantigens 22 An Overview I. Conditions for Deriving T Cell Clones II. Cytolytic T Cell Clones III. Noncytolytic T Cell Clones IV. Factors Produced by Alloreactive T Cell Clones V. Conclusions References 23 Cloned Continuous Lines of H-2 -Restricted Influenza Virus-Specific CTL: Probes of TLymphocyte Specificity and Heterogeneity I. Properties of Influenza-Specific CTL Clones II. Conclusions References 24 Cytolytic T Lymphocyte Clones Recognizing Murine Sarcoma Virus-Induced TumorAntigens I. Optimal Microculture Conditions for the Generation of MoLV-Specific CTL Clones II. Frequency Determination of MoLV-Specific CTL Precursors III. Isolation and Maintenance of MoLV-Specific CTL Clones IV. Specificity of MoLV-Specific CTL Clones V. Surface Phenotype of MoLV-Specific CTL Clones VI. Conclusions References 25 The Specificity Repertoire of Cytolytic T Lymphocytes I. Analysis of Receptor Specificity II. CTL Receptor Repertoire of the B10.D2 Anti-H-2Kb Response III. Specificity Repertoire of the bmll Anti-H-2Kb Response IV. The C57BL/6 Anti-bmll CTL Response: A Model for Determinant Recognition V. The Influence of MHC on Receptor Repertoire References 26 Alloreactive T Cell Clones Which Recognize Hybrid Determinants Text References 27 Anti-H-2 Reactivity of Mis-Specific T Cell Clones I. H-2 Specificity of Uncloned Mis-Reactive T Cell Lines II. Anti-H-2 and Anti-Mis Reactivity of T Cell Clones III. Characteristics of Cloned Mis-Reactive T Cell Lines IV. Conclusions References 28 Lymphokine Production by Cytolytic and Noncytolytic Alloreactive T Cell Clones I. Analysis of Lymphokine Production by a Noncytolytic T Cell Clone and Its Variant upon Alloantigenic Stimulation II. Analysis of Lymphokine Production by Noncytolytic and Cytolytic Alloreactive T Cell Clones after Stimulation with Mitogen III. Biological Separation of Lymphokine Activities Using Different T Cell Clones IV. Heterogeneity of Cell Clones Producing Lymphokines V. Conclusions ReferencesVI. Murine T Cell Clones Reactive with Soluble Antigens 29 An Overview Text References 30 An Analysis of T Cell Antigen Recognition Utilizing T Cell Clones I. Experimental Design II. T Cell Antigen Specificity III. Conformational Requirements of T Cell Antigen Recognition IV. Antigen-Presenting Cell Function V. Ia Restriction and Ir Gene Function VI. Conclusions References 31 Alloreactivity of Antigen-Specific T Cell Clones Text References 32 Mechanism of B Cell Activation by Monoclonal T Helper Cell Populations I. KLH-Specific Cloned T Cells Provide H-2 Restricted Help for Antibody Responses to TNP-KLH II. Cloned Th Cells Can Be H-2 Restricted in Their Recognition of Accessory Cells but Not B Cells III. After Specific Activation T Cell Clones Can Provide Antigen-Nonspecific Helper Activity IV. Cloned Th Cell Supernatant Mediates Antigen- Nonspecific Help V. Cloned Th Cells Can Function through a Pathway Requiring Lyb-5 + B Cells VI. The Same Cloned Th Cells Function through Pathways Which Are either Restricted or Unrestricted for T h Cell Recognition of B Cell MHC Determinants 391 VII. The Same Cloned Th Cells Function through Pathways Which Activate Different B Cell Subpopulations VIII. Conclusions References 33 T Cell Lines and T Cell Clones Bearing Cross- Reactive Idiotype I. Functional Characterization of the Helper Activity of Cell Line L.14 II. L.14 Cells Expressing Idiotypic-Like Determinants III. Effect of Anti-Idiotypic Serum B658 on the Activity of Clone C.14.14 IV. Conclusions References 34 Specific Regulation of Immune Responses by Products of T Cell Clones Text ReferencesVII. Human T Cell Clones 35 Cloning of T Lymphocytes in Man I. PLT-Reactive Clones II. Cytotoxic (CTL) Clones III. Conclusions References 36 Human T Cell Clones: Function, Specificity, and Cell Surface Markers I. T Cell Clones Obtained Following Sensitization in Vitro II. T Cell Clones following in Vivo Immunization III. Surface Markers of Human T Cell Clones: Monoclonal Antibodies (mAB) Interacting with the Cytolytic Function IV. Conclusions References 37 Human T Cell Clones Reactive with Soluble Antigens: Methodology, Specificity, and MHC Restriction I. Antigen Specificity of Soft Agar Colonies of Human T Cells II. Genetic Requirements for Antigen Stimulation References VIII. Future Perspectives in the Utilization of T Cell Clones 38 Potential Use of Expanded T Lymphoid Cells and T Cell Clones for the Immunotherapy of Cancer I. Traffic in Vivo of Cells Grown in T Cell Growth Factor II. Effect in Vivo of Adoptively Transferred Cells Expanded in T Cell Growth Factor III. Isolation of T Lymphocyte Clones Specifically Reactive with Tumor IV. The Lysis of Fresh Syngeneic or Autologous Tumor Cells by Lymphoid Cells Expanded in T Cell Growth Factor V. Conclusions References 39 Cloned T Cells as a Tool for Molecular Geneticists: Approaches to Cloning Genes Which Encode T Cell Antigen Receptors I. Immunoglobulin Expression in Cloned T Cells II. Cloning Nonimmunoglobulin Genes from T Cells III. Conclusions References IX. Appendix I. Factors which Influence the Growth of T Lymphocyte Clones A. Assay for Interleukin-1 (IL-1) B. T Cell Lymphoma Model for the Analysis of Interleukin-1 (IL-1) C. Preparation of TCGF from Rat Spleen Cells D. Preparation of TCGF from a T Cell Tumor (EL-4) E. Production of Human TCGF F. Preparation of TCGF from Human Spleen Cells G. IL-2 Microassay H. Purification and Characterization of IL-2 II. Cell Fusion as a Technique for Generation of T Cell Clones A. Production of Antigen-Specific, H-2 Restricted T Cell Hybridomas III. Clonal Analysis by Limiting Dilution A. Measurement and Calculation of CTL-P Frequencies B. Limit Dilution Analysis of Functional T Cell Precursors C. Limit Dilution Analysis of T Cells Releasing Lymphokines IV. Murine T Cell Clones Reactive with Alloantigens A. Clones of Noncytolytic Alloreactive Murine T Cells B. Cloning of Alloreactive Murine T Cells C. Isolation of Virus-Specific CTL Clones V. Murine T Cell Clones Reactive with Soluble Antigens A. Immunization and Long-Term Culture of Murine Immune Lymph Node Cells B. Cloning of Soluble Antigen-Reactive Murine T Inducer (Th) Cells C. Soft Agar Technique for Obtaining Antigen-Specific T Cell Clones VI. Human T Cell Clones Reactive with Alloantigens and Soluble Antigens A. Cloning of Alloreactive Human T Cells B. Cloning and Expansion of Human Alloreactive T Lymphocytes C. Establishment of Colonies of Antigen-Reactive Human T CellsIndex

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