Immunoglobulins

Since the discovery more than thirty years ago that antibody actlvlty could be localized to discrete plasma protein fractions, the study of immunoglobulin struc­ ture and function has dominated the field of immunochemistry. During this time, sources of homogeneous immunoglobulin molecules have been discovered, the subunit nature of the proteins has been defined, and the three-dimensional struc­ tures of the antigen-recognition portion of several antibody molecules have been elucidated. Insights into the complicated genetic control of these proteins are being gained rapidly through analysis of amino acid sequences of naturally occurring and induced homogeneous immunoglobulins. Immunoglobulins have been analyzed by protein chemists as models of complex multimeric systems, examined by geneticists studying serum protein polymorphisms, and employed by molecular biologists as highly selective probes capable of distinguishing minor features of molecular topog­ raphy. Clinical applications have ranged from the now routine quantitation of immunoglobulin levels to the use of antibodies to detect trace levels of a variety of natural products and drug metabolites. All these applications have depended ulti­ mately on a thorough understanding of the immunoglobulin and its antigen-combin­ ing site. To cover the entire field of immunoglobulin structure and function would require many volumes this size; therefore, subjects presented in this volume represent those which we felt contribute most to our current understanding of this protein family. The first chapters deal with the structure and function of the immunoglobulin molecule.

1 Studies on the Three-Dimensional Structure of Immunoglobulins.- 1. Introduction.- 2. X-Ray Crystallographic Techniques.- 3. Immunoglobulins and Fc Fragments.- 4. Three-Dimensional Structure of Light Chains.- 5. Fab Fragments.- 6. Antibody Combining Sites.- 7. Structure of Fab-Hapten Complexes.- 8. Structure and Genetic Control of VL and VH Regions.- 9. Conclusions.- 10. Note Added in Proof.- References.- 2 Solution Conformation and Segmental Flexibility of Immunoglobulins.- 1. Introduction.- 2. Immunoglobulin G.- 3. Immunoglobulin M.- 4. Immunoglobulin A.- 5. Immunoglobulin D.- 6. Immunoglobulin E.- 7. Concluding Remarks.- References.- 3 The Affinity of Antibody: Range, Variability, and the Role of Multivalence.- 1. Introduction.- 2. Affinity for Monovalent Ligands.- 3. Role of Multivalence.- 4. Structural Analysis of Combining Sites.- 5. Closing Statement.- References.- 4 Antibody Combining Regions.- 1. Background.- 2. Structural Properties of Antibody Combining Regions.- 3. Structural and Functional Correlates of Antigen-Binding.- 4. Biological Significance of Antigen-Binding.- 5. Summary.- References.- 5 The Secretory Component and the J Chain.- 1. Introduction.- 2. The Secretory Component.- 3. The J Chain.- References.- 6 The Structural Basis for the Biological Properties of Immunoglobulins.- 1. Introduction.- 2. Nature of Immunoglobulin Biological Properties.- 3. Submolecular Localization of Immunoglobulin Biological Properties.- 4. Summary and Conclusions.- References.- 7 The Significance of Gene Duplication in Immunoglobulin Evolution (Epimethean Natural Selection and Promethean Evolution).- 1. Introduction.- 2. Epimethean Nature of Evolution by Natural Selection.- 3. Why the Promethean Evolution of the Immune System?.- 4. Strategy of Promethean Evolution.- 5.Conclusions.- References.- 8 The Phylogenetic Origins of Immunoglobulin Structure.- 1. Introduction.- 2. Invertebrate Humoral Immunity—Agglutinins.- 3. Immunoglobulins of Ostracoderm-Derived Vertebrates.- 4. Immunoglobulins of Placoderm-Derived Vertebrates.- 5. Conformation and Active Sites.- 6. Proteolytic Cleavage Products of Immunoglobulins from Lower Species.- 7. Primary Structure.- 8. Cell-Surface Immunoglobulin and Immunoglobulin-Related Structure(s).- 9. Summary and Conclusions.- References.- 9 Evidence for and the Significance of ‘Two Genes, One Polypeptide Chain’.- 1. Basic Immunoglobulin Units.- 2. History.- 3. Allotypes of Rabbit Heavy-Chain Variable Regions.- 4. Sharing of a Single Constant Region by Variable Regions.- 5. Sharing of a Single Variable Region by Constant Regions.- 6. Reciprocal Sharing of Variable and Constant Regions in Heavy Chains.- 7. DNA-RNA Hybridization.- 8. Fusion of the Variable and Constant Regions.- 9. Three Linkage Groups.- 10. More Than Two Genes for One Polypeptide Chain?.- 11. Specific Gene Activation and Differential Gene Expression.- 12. Genetic Switch.- 13. Summary.- References.- 10 Structure of Atypical Immunoglobulins—Relationship to Genetic Control Mechanisms.- 1. Introduction.- 2. Heavy-Chain Variants: Heavy-Chain-Disease Proteins.- 3. Myelomas with Altered Heavy Chains.- 4. Myelomas with Altered Light Chains.- 5. Hybrid Molecules.- 6. Nonsecretors.- 7. Discussion.- References.- 11 Patterns of Sequence Variability in Immunoglobulin Variable Regions: Functional, Evolutionary, and Genetic Implications.- 1. Introduction.- 2. Variable Regions Defined: Molecular Limits and Phylogenetic Occurrence.- 3. Variable Region-Constant Region Transition.- 4. Subgroups Defined and Their Distribution in Phylogeny.- 5.Phylogenetically Associated Residues.- 6. Nature of Idiotypy and Its Relationship to Hypervariable Regions and the Antibody Combining Site.- 7. Genetic Origin of Variable-Region Sequence Diversity.- 8. Conclusions.- References.- 12 Genetic Control of Immunoglobulin Synthesis in Man.- 1. Introduction.- 2. Evidence for Genetic Control of Antibody Synthesis in Experimental Animals.- 3. Evidence for Genetic Control of Immunoglobulin Synthesis in Man.- References.- 13 Heavy-Chain Variable (VH) Subgroups among Myeloma Proteins, Antibodies, and Membrane Immunoglobulins of Lymphocytes.- 1. Introduction.- 2. Anti-VH-Subgroup Antisera.- 3. Comparison of VH Subgroups of the Same Proteins Determined Serologically and by Amino Acid Sequence Analysis.- 4. Serologically Determined VH Subgroups in Myeloma Proteins with Previously Unknown VH Subgroups.- 5. Relative Amounts of the VH Subgroups in Different Human Sera.- 6. Restriction of Immune and Natural Human Antibodies for VH Subgroups.- 7. VH Subgroups of Membrane Immunoglobulin of Normal Human Lymphocytes.- 8. VH Subgroups of Membrane Immunoglobulin of Chronic Lymphocytic Leukemia Cells.- 9. Comments.- References.- 14 Cryoglobulins and Pyroglobulins.- 1. Cryoglobulins.- 2. Pyroglobulins.- References.- 15 Biosynthesis and Secretion of Immunoglobulins.- 1. Introduction.- 2. Methods.- 3. Synthesis of Light and Heavy Polypeptide Chains.- 4. Assembly of Immunoglobulin Molecules.- 5. Secretion of Immunoglobulins.- 6. Differentiation of B Lymphocytes.- References.- 16 Lymphocyte Membrane Immunoglobulins: An Overview.- 1. Introduction.- 2. Basic Data on Membrane Immunoglobulins.- 3. Cells That Carry Actively Synthesized Membrane Immunoglobulins.- 4. Membrane Immunoglobulin Idiotypes, Allotypes, and Isotypes.- 5. Effects of the Interactionbetween Membrane Immunoglobulins and Antiimmunoglobulin Antibodies.- References.