Current Trends in Histocompatibility : Volume 2 Biological and Clinical Concepts

Information about histocompatibility antigens is expanding so rapidly that of all advances. In these volumes, we have it is difficult to remain abreast made an effort to bring together the most current work on topics that have generated most of the recent advances and discussions. We have asked each author to present and interpret his most current work, and we have judiciously refrained from imposing our own prejudices and viewpoints. Although there is obvious overlap in some individual topics, we have encouraged this to provide the reader with as many different and some­ times opposing viewpoints as possible. This approach will, we hope, give a broad overview of current ideas in the field. We wish to thank all contributors for their timely and exciting manu­ scripts, and we sincerely hope that the reader will benefit from these volumes. R. A. Reisfeld S. Ferrone La Jolla vii Contents I. Role of Histocompatibility Antigens in Cell-Cell Interaction Chapter 1 Histocompatibility Antigens and the T-Cell Repertoire . . . . . . . . . . . . . . 3 Harald von Boehmer 1. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2. H-2 Restriction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2. 1. H-2 Restriction of T Cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2. 2. B Cells Are Not H-2-Restricted . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 3. H-2-Linked Ir Genes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 3. 1. Influence on the T-Cell Repertoire . . . . . . . . . . . . . . . . . . . . . . . . 5 3. 2. H-2-Gene Complementation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 3. 3. The B-Cell Repertoire Is Not Directly Influenced by H-2-Linked Ir Genes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 4. Frequency of Cells Specific for Allogeneic H-2 Antigens . . . . . . . . 12 4. 1. Allospecific T Cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 4. 2. Allospecific B Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

I. Role of Histocompatibility Antigens in Cell-Cell Interaction.- 1 Histocompatibility Antigens and the T-Cell Repertoire.- 1. Introduction.- 2. H-2 Restriction.- 2.1. H-2 Restriction of T Cells.- 2.2. B Cells Are Not H-2-Restricted.- 3. H-2-Linked Ir Genes.- 3.1. Influence on the T-Cell Repertoire.- 3.2. H-2-Gene Complementation.- 3.3. The B-Cell Repertoire Is Not Directly Influenced by H-2-Linked Ir Genes.- 4. Frequency of Cells Specific for Allogeneic H-2 Antigens.- 4.1. Allospecific T Cells.- 4.2. Allospecific B Cells.- 5. T-Cell Repertoire for Restricting Elements vs. the Repertoire for Allogeneic H-2 Antigens.- 6. T-Cell vs. B-Cell Repertoire.- 6.1. Probing of the Repertoire by Responsiveness.- 6.2. Probing of the Repertoire by v-Gene Markers on Responding Cells.- 7. Conclusions.- References.- 2 Continuously Proliferating Allospecific T-Cell Lines: A Model to Study T-Cell Functions and Receptors.- 1. Introduction.- 2. Properties of Allospecific T-Cell Lines.- 2.1. Initiation of Allospecific T-Cell Lines.- 2.2. Requirements for Cell Proliferation in Long-Term T-Cell Cultures.- 2.3. Cytotoxic Potential of Allospecific T-Cell Lines.- 2.4. Selection of Allospecific T-Cell Lines over Extended Periods of Time.- 2.5. Cell-Surface Molecules of Allospecific T-Cell Lines.- 3. Outlook.- References.- 3 The Dual Specificity of Virus-Immune T Cells: Functional Indications That Virus and H-2 Molecules May Associate on the Cell Membrane.- 1. Introduction.- 2. The Influenza Model.- 2.1. Characteristics of Influenza Viruses.- 2.2. Specificity of Influenza-Immune T Cells.- 2.3. Responder-Nonresponder Situations.- 2.4. Blocking Cytotoxicity with Monospecific Antisera.- 3. Negative Selection of Alloreactive Precursors.- 3.1. Rationale.- 3.2. Responsiveness in Allogeneic Situations.- 4. General Discussion.- 5. Summary.- References.- 4 Hapten Recognition by Cytotoxic T Cells: The Modifying Influence of the Major Histocompatibility Complex.- 1. Introduction.- 2. Materials and Methods.- 2.1. Preparation of Liposomes.- 2.2. Preparation of Haptenated Bovine Serum Albumin.- 2.3. Purified Anti-DNP Antibody.- 2.4. [125I]-Anti-DNP Antibody.- 2.5. Membrane-Vesicle Preparation.- 2.6. Binding of [125I]-Anti-DNP Antibody to Haptenated Cells.- 2.7. C-Mediated and K-Cell-Mediated Cytolysis.- 2.8. Generation of Hapten-Specific Cytotoxic Responses.- 2.9. T-Cell Mediated Cytolytic Assays.- 3. Results.- 3.1. Hapten Presentation on Target Cells after Direct Chemical Modification and after Interaction with Dinitrophenylated Liposomes and Dinitrophenylated Protein.- 3.2. Generation of a Primary Hapten-Specific Cytotoxic Response in Vitro Using a Variety of Hapten-Bearing Stimulator Cells.- 3.3. Target Cells “Haptenated” by Various Procedures: Their Susceptibility to Lysis by H-2-Restricted, Hapten-Specific Cytotoxic T Lymphocytes.- 3.4. Attempts to Inhibit Hapten-Specific Cytolysis with Haptenated Cells.- 4. Discussion.- References.- 5 New Thoughts on the Control of Self-Recognition, Cell Interactions, and Immune Responsiveness by Major Histocompatibility Complex Genes.- 1. Introduction.- 2. Self-Recognition and Cell-Cell Interactions.- 3. Concept of Adaptive Differentiation.- 4. Relevance of the Proposed Mechanisms of Adaptive Differentiation to Certain Unresolved Immunological Puzzles.- 5. Recognition Mechanisms in the Immune System.- 6. Some Current Thoughts on Ir Genes.- 7. Some New Observations on Ir-Gene Mechanisms.- 8. Conclusions.- References.- 6 The Role of Cell-Surface Antigens in Progressive Tumor Growth (Immunological Surveillance Re-revisited).- 7 Self-HLA-D-Region Products Restrict Human T-Lymphocyte Activation by Antigen.- 1. Introduction.- 2. The HLA-D/DR and Rodent I-Region Cell-Membrane Products Are Analogous.- 3. Self-HLA-D/DR Restriction of T Cells Sensitized in Vivo.- 3.1. The T-Cell Proliferative Response to PPD in Vitro Is Macrophage-Dependent.- 3.2. The Antigen-Presenting Macrophages Must Share at Least One HLA-D/DR Determinant with the T-Cell Donor.- 3.3. Lack of Cooperation between Cells from HLA-D-Disparate Donors Is Not Due to Suppression or Cytotoxicity Caused by the Allogeneic Responses.- 3.4. Anti-DR Antibodies Will Specifically Inhibit the Antigen-Specific Response.- 3.5. Clonal Distribution of HLA-D/DR-Restricted Antigen-Specific T-Cells.- 3.6. B Lymphocytes Expressing Self-HLA-D Are Not Able to Substitute for Macrophages in Antigen Activation.- 4. Self-HLA-D/DR Restriction of T Cells Sensitized in Vitro.- 4.1. In Vitro Priming against TNP-Treated Autologous Cells.- 4.2. HLA-D/DR Restriction of the TNP-Specific Response.- 4.3. Is the TNP-Specific Response Also Restricted by HLA-A,B,C?.- 4.4. Can B Cells Substitute for Macrophages in the Secondary TNP-Specific Response?.- 5. Comments.- 6. Implications.- 7. Conclusion.- References.- 8 How Strict is the MHC Restriction of T Cells?.- 1. Introduction.- 2. Materials and Methods.- 2.1. Mice.- 2.2. Virus and Immunization.- 2.3. Chimeras.- 2.4. Cell Preparations and H-2 Typing.- 2.5. Cytotoxicity Assay.- 2.6. Antiviral Protection Assay in Vivo.- 2.7. Statistical Methods.- 3. Results.- 3.1. Quantitation of the Restriction Specificity Expressed in Vivo and in Vitro by Virus-Specific Cytotoxic T Cells from Unmanipulated Mice.- 3.2. Comparison of the Restriction Specificities Expressed by Virus-Specific Cytotoxic T Cells from Chimeric Mice.- 4. Discussion.- References.- II. Clinical Aspects of Transplantation: Association with Disease.- 9 The Role of Histocompatibility Antigens in Clinical Transplantation.- 1. Introduction.- 2. HLA-A and -B Matching.- 3. HLA-D Matching.- 4. Blood Transfusions.- References.- 10 HLA-Linked Regulation of Immune Responsiveness in Man: Role of I-Region-Gene Products.- 1. Introduction.- 2. Association between HLA and Immune Response.- 2.1. Response to Ethical Antigens.- 2.2. Response to Skin-Test Antigens.- 2.3. Conclusion.- 3. Immunogenetics of Response to Streptococcal Antigens.- 3.1. Purification and Characterization.- 3.2. PSA-C Response in Families.- 3.3. Mechanisms of Response to Streptococcal Antigens.- 3.4. Conclusion.- References.- 11 Clinical Histocompatibility Testing in Renal Transplantation: Potential Keys to Alloimmune Specificity and Reactivity.- 1. Introduction.- 2. Pretransplant Immunological Assessment.- 2.1. Donor-Specific Resistance.- 2.2. General (Nonspecific) Host Immune Competence.- 3. Posttransplantation Immunological Assessment.- 3.1. Donor-Specific Immune Monitoring.- 3.2. Nonspecific Immune Monitoring.- 4. Summary.- References.- 12 Human Ia-like Alloantigens and Their Medical Significances.- 1. Introduction.- 2. Human Ia-like Alloantigens.- 3. Merrit Alloantigenic System.- 4. Relationship of Ia-like Alloantigenic Systems to the HLA Complex.- 5. Seventh International Histocompatibility Workshop and HLA-DRw Specificities.- 6. Correlation between HLA-D and DRw.- 7. Ia-like Alloantigenic Segregants Distinct from HLA-DR.- 8. Leukemia Cells and Ia-like Alloantigens.- 9. Ia-like Alloantigens and Nonmalignant-Disease Associations.- 10. HLA and Cancer: New Considerations.- 11. Major Histocompatibility Complex, Aging, and DNA Repair.- References.- 13 The Enigma of Good Kidney-Graft Survival in the Face of Poor HLA Matches: HLA Matching for Kidney Transplantation Makes Sense.- 1. Introduction.- 2. Blood Transfusion.- 3. HLA-DR Matching.- 4. Incompatibility for Non-HLA Determinants.- 5. Discussion and Conclusions.- References.- 14 Histocompatibility Antigens and Susceptibility to Disease―Genetic Considerations.- 1. Introduction.- 2. General Considerations.- 2.1. HLA Association at the Population Level.- 2.2. Distribution of HLA Phenotypes within the Patient Sample.- 2.3. Studies of Linkage.- 2.4. Affected Sibpair Method.- 3. Relationships between HLA and Specific Diseases.- 3.1. Complement Factor 2 Deficiency.- 3.2. Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency.- 3.3. Idiopathic Hemotochromatosis.- 3.4. Ankylosing Spondylitis.- 3.5. Insulin-Dependent Diabetes.- 3.6. Multiple Sclerosis and Optic Neuritis.- 4. Concluding Remarks.- References.