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Journal ArticleDOI

A Genetic Marker in the Variable Region of Light Chains of Mouse Immunoglobulins

01 Nov 1970-Proceedings of the National Academy of Sciences of the United States of America (National Academy of Sciences)-Vol. 67, Iss: 3, pp 1192-1199
TL;DR: A genetic variation was observed upon autoradiographic comparison of tryptic peptide maps of (14)C-labeled normal light chains from 17 different inbred strains of mice and breeding experiments showed that the difference segregated in a classical Mendelian fashion.
Abstract: A genetic variation was observed upon autoradiographic comparison of tryptic peptide maps of 14C-labeled normal light chains from 17 different inbred strains of mice. The difference was found in strains AKR/J, C58/J, and RF/J. Chemical analyses showed that the differences were in a region of the amino acid sequence in the neighborhood of half-cystine I of the variable region of the light chain. Breeding experiments showed that the difference segregated in a classical Mendelian fashion.
Citations
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Book ChapterDOI
TL;DR: The immunoglobulin classes and subclasses represent a group of structurally related proteins, and in all instances consist of two pairs of polypeptide chains held together by disulfide bridges and noncovalent forces.
Abstract: Publisher Summary The immunoglobulin classes and subclasses represent a group of structurally related proteins, and in all instances consist of two pairs of polypeptide chains held together by disulfide bridges and noncovalent forces. The immunoglobulins can be classified according to three different parameters related to different antigenic and biochemical structures: (1) heavy-chain C regions constitute the basis for the different classes and subclasses; (2.) light-chain C regions specify the types or subtypes; and (3.) variable regions of both heavy and light chains can be divided into different groups and subgroups. Immunoglobulin G is the major immunoglobulin class making up about 80% of serum immunoglobulin. There are four subclasses of immunoglobulin G that were first distinguished by antigenic differences. These also show distinct peptide and amino acid differences and differences in biological activities that are discussed in details in the chapter. Immunoglobulin A is the dominant immunoglobulin class in secretions and may be present in serum as a monomer or polymer. The antigenic properties of the immunoglobulins can be divided into three main categories: (1) antigens present in all normal sera are called “isotypes;” (2) antigens present in some but not in all normal sera and segregate as if controlled by allelic genes are called “azlotypes;” (3) antigenic properties related to one particular antibody population are called “individual specificities” or “idiotypes.”

297 citations

Journal ArticleDOI
TL;DR: The localization of distinct regions which markedly influence the nature of the antigenicity of the light chain molecule provides a molecular basis for the observed heterogeneity among κ chains and contributes to the knowledge of the tertiary structure of the polypeptide chain.
Abstract: Abstract The evaluation of numerous anti-κ chain antisera through immunochemical studies of κ light chains for which complete or partial sequence data were available has resulted in the localization of three distinct regions in the variant half of the light chain which are associated with specific antigenic sites. The residue at position 9 appears to be associated with an antigenic site which, in general, may be termed a group-related antigenic site. The residues at positions 45 and 94 through 96 are associated with two distinct antigenic sites which are recognized specifically by numerous antisera and are responsible for certain intergroup similarities and intragroup differences among κ chains. Many of the antisera readily distinguish among proteins which have been structurally assigned to the same subgroup. The localization of distinct regions which markedly influence the nature of the antigenicity of the light chain molecule provides a molecular basis for the observed heterogeneity among κ chains and contributes to the knowledge of the tertiary structure of the polypeptide chain.

176 citations

Book ChapterDOI
TL;DR: This chapter explains allotypic phenomena adequately by involving regulator genes in the linkage, somatic recombination, and selective gene expression that have been observed in genetic studies employing allotypes.
Abstract: Publisher Summary This chapter presents the allotypic studies in the rabbit and offers more detailed information on several specific topics to which allotypic studies have contributed. The chapter focuses on the rabbit allotypes and gives an overview of the developments. There is a paucity of structural information on rabbit immunoglobulins and an optimal amount of genetic information has been obtained in studies on this species by the use of the immunoglobulin antigenic markers. The chapter explains allotypic phenomena adequately by involving regulator genes in the linkage, somatic recombination, and selective gene expression that have been observed in genetic studies employing allotypes. It is difficult to visualize these complex genetic relationships in terms of the repressors and corepressors that have been described for nonmammalian systems involving regulation. The possibility has been raised that rabbit immunoglobulin allotypes are not products of allelic structural genes, however are products of regulator genes. The studies on allotypes and idiotypes have made significant contributions to the knowledge of genetic control of immunoglobulin synthesis, knowledge that is, in many instances, relevant to more general biological topics.

147 citations

Journal ArticleDOI
TL;DR: The results suggest close linkage of VH and CH genes and the cross-reactive idiotype was found in nearly all F1 mice tested, suggesting that idiotype must be a function of V region sequences.
Abstract: Anti-p-azophenylarsonate (anti-Ar) antibodies elicited in all strain A/J mice tested share one or more idiotypic specificities. These specificities are also found in the anti-Ar antibodies of mice of the closely related strain, AL/N, but not in those of BALB/c mice. Anti-Ar antibodies were elicited in congenic mice in which the IgCH locus of AL/N mice, which controls allotypic markers in the constant regions of heavy chains, had been introgressively backcrossed for nine generations onto a BALB/c background; the mice were then rendered homozygous for the AL/N allotypic determinant. On the average, these antibodies were quantitatively equivalent, with respect to content of the cross-reactive idiotype, to those of AL/N mice. This indicates that the gene controlling the idiotype is closely linked to the IgCH locus. Since idiotype must be a function of V region sequences, the results suggest close linkage of VH and CH genes. The cross-reactive idiotype was found in nearly all F1 mice (C57/BL x A/J or BALB/c x A/J) tested.

140 citations

Book ChapterDOI
TL;DR: Based on the investigations of I-E and Mls tolerance-related Vβ clonal deletions, the chapter proposes that the abnormally proliferating, autoimmunity-inducing/enhancing double-negative TcR α:β + lpr and gld cells are not related to immature CD4 - 8 - thymocytes, but instead are derived from CD4 + 8 + precursors through a process resulting in down-regulation of both accessory molecules.
Abstract: Publisher Summary The chapter that addresses the Ig germ line gene organization in lupus-prone strains of mice suggested that the disease can develop in different Ig heavy and light chain haplotypes, and that the Ig germ line genes in lupus mice are probably normal. Analyses of the Ig gene segments expressed in monoclonal autoantibodies from autoimmune mice revealed that similar, moreover, in some instances even identical, gene segments are expressed in autoantibodies and in antibodies to exogenous antigens, and that antiself and antiforeign responses are encoded by the same, or at least an overlapping, germ line gene repertoire. Evidence has been obtained that, in an individual lupus mouse, the number of autoantibody-secreting clonotypes decreases after class switch, while that of productive mutations increases, suggesting that antiself responses might be (auto) antigen-driven responses, but this conclusion should be considered tentative. Finally, based on the investigations of I-E and Mls tolerance-related Vβ clonal deletions, the chapter proposes that the abnormally proliferating, autoimmunity-inducing/enhancing double-negative TcR α:β + lpr and gld cells are not related to immature CD4 - 8 - thymocytes, but instead are derived from CD4 + 8 + precursors through a process resulting in down-regulation of both accessory molecules.

122 citations

References
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Journal ArticleDOI
TL;DR: An hypothesis is presented to relate the structural features of the various γ-globulins in terms of the multiplicity of polypeptide chains in these molecules.
Abstract: When human and rabbit 7S γ-globulins were reduced in strong urea solutions by a number of procedures, their molecular weights fell to approximately ⅓ of the original values. Partial separation of the reduction products was achieved using chromatography and starch gel electrophoresis in urea solutions. One of the components of reduced human 7S γ-globulin was isolated by chromatography, identified by starch gel electrophoresis, and subjected to amino acid analyses. The amino acid composition of this component differed from that of the starting material and also from that of the remaining components. A reduced pathological macroglobulin dissociated to components with an average molecular weight of 41,000. Several reduced human myeloma proteins, when subjected to starch gel electrophoresis, yielded individual patterns that nevertheless had features in common with those of reduced normal γ-globulins. Reduction of normal and abnormal γ-globulins was accompanied by the appearance of titratable sulfhydryl groups. Chemical treatments other than reduction were used to determine the type of bond holding the subunits together. It was tentatively concluded that they were linked by disulfide bonds. An hypothesis is presented to relate the structural features of the various γ-globulins in terms of the multiplicity of polypeptide chains in these molecules.

382 citations

Journal ArticleDOI

320 citations

Journal ArticleDOI
17 Apr 1970-Science
TL;DR: The monument at Borrowston Rig requires anchor points that are placed farther apart on the circumference than the intersections made by the trisecting radii demand, and Thom presents a good argument for use of a standard length of 2.72 feet in the construction of these structures.
Abstract: 1. S. P. 6 Ri6rdfiin and G. Daniel, New Grange (Praeger, New York, 1964). 2. G. Hawkins, Stonehenge Decoded (Doubleday, Garden City, N.Y., 1965). 3. A. Thom, Megalithic Sites in Britain (Oxford, London, 1967). 4. G. Daniel, The Megalithic Builders of Western Europe (Hutchenson, London, 1959), pp. 111-113. 5. Actually this tumulus represents what Thom calls a type D ring, one in which the two pivot stakes are placed at one-third the radius from a, rather than at the midpoint. As Fig. 3 shows, the pivots can be kept at the midpoint of the radius if a, is allowed to move inside the design. 6. L. B. Borst, Science 163, 567 (1969). 7. The monument at Borrowston Rig requires anchor points that are placed farther apart on the circumference than the intersections made by the trisecting radii demand. In this design the circle of the smaller end arc passes through the center of the larger end arc, and the wider placement of the anchor stakes may have been made on this account. The site at Maen Mawr had anchor stakes that were closer together on the circumference. If the radial line from P2 to either anchor is taken as a hypotenuse of a right triangle one side of which is half the anchor line, then the lengths of the sides of this triangle (in megalithic half-yards) are 14, 17, and 22, which is nearly Pythagorean (142+ 172= 485e 484). 8. M. Gardner, Sci. Amer. 221, 239 (1969). 9. To mention one such consequence, with the megalithic method concentric rings, such as those found at Woodhenge, can be drawn without using any special mensuration technique. That is, a rope can be lengthened by an unspecified amount and a concentric design can be drawn at once. With a flexible compass, on the other hand, the large arc in a type II egg, for example, can be drawn without special measurement but the other arcs must be changed by x amount to remain equidistant from the perimeter of the original figure. 10. Thom presents a good argument for use of a standard length of 2.72 feet (one megalithic yard) in the construction of these structures, as well as of others in both the Old World and the New. 11. The writing of this article was supported in part by the Oklahoma State University Research Foundation.

195 citations

Journal ArticleDOI
28 Oct 1967-Nature
TL;DR: Data now seem to require at least three versions of the same section of the molecule, and the simplest involves recombination between the elements of an “antibody gene pair” containing two version of the variable section ofThe molecule.
Abstract: Crossing over theories have been advanced to explain antibody variability, and the simplest involves recombination between the elements of an “antibody gene pair” containing two versions of the variable section of the molecule. Data now seem to require at least three versions of the same section.

185 citations

Journal ArticleDOI
25 Jul 1970-Nature
TL;DR: A review of the structural and genetic properties of the immunoglobulins suggests that somatic recombination is fundamental in the selective immune response.
Abstract: A review of the structural and genetic properties of the immunoglobulins suggests that somatic recombination is fundamental in the selective immune response.

147 citations