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Idiotypic Determinants, Minigenes, and the Antibody Combining Site

  • Elvin A. Kabat

Abstract

Idiotypic determinants, idiotopes, are best defined as antigenic determinants located on the Fv fragment of an antibody molecule. Since the demonstration that myeloma antibodies from different individuals showed characteristic distinct antigenic specificities(1,2) and the subsequent findings that such antigenic determinants were present on induced antibodies(3–5) they have posed a structural and genetic problem, the solution of which is crucial to our understanding not only of the three-dimensional aspects of antibody structure but also of the regulation of antibody synthesis, the maintenance of antibody levels, and the rise and fall of antibody populations with combining sites of slightly different specificities. Most intriguing is the possibility that nature has made use of similar principles in other ligand-receptor interactions. Although there is little evidence for this at the moment, recent studies(6–11) indicate that anti-idiotypic antibodies formed against antibodies to hormones, agonists, and antagonists, which interact with specific receptors on the cell surface, show a specificity which may structurally resemble a portion of the hormone.

Keywords

Antigenic Determinant Cold Agglutinin Total Binding Energy Myeloma Protein Variable Region Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Lohss, F., Weiler, E., and Hillmann, G., 1953, Myelom-Plasma-Proteine. III. Mitteilung zur Immuno- chemie der γ.-myelom-Proteine, Z. Naturforsch. Teil B 8:625–631.Google Scholar
  2. 2.
    Slater, R. J., Ward, S. M., and Kunkel, H. G., 1955, Immunological relationships among the myeloma proteins, J. Exp. Med. 101:85–108.PubMedGoogle Scholar
  3. 3.
    Oudin, J., and Michel, M., 1963, Une nouvelle forme d’allotypie des globulines y du serum de lapin apparemment liee a le fonction et a la specificite anticorps, C.R. Seances Soc. Biol. Paris 257:805–808.Google Scholar
  4. 4.
    Kunkel, H. G., Mannik, M., and Williams, R. C., 1963, Individual antigenic specificity of isolated antibodies, Science 140:1218–1219.PubMedGoogle Scholar
  5. 5.
    Gell, P. G. H., and Kelus, A. S., 1964, Anti-antibody or clone-product?, Nature 201:687–689.PubMedGoogle Scholar
  6. 6.
    Sege, K., and Peterson, P. A., 1978, Use of anti-idiotypic antibodies as cell-surface receptor probes, Proc. Natl. Acad. Sci. USA 75:2443–2447.PubMedGoogle Scholar
  7. 7.
    Schreiber, A. B., Couraud, P. O., André, C., Vray, B., and Strosberg, A. D., 1980, Anti-alprenolol anti- idiotypic antibodies bind to β-adrenergic receptors and modulate catecholamine-sensitive adenylate cyclase, Proc. Natl. Acad. Sci. USA 77:7385–7389.PubMedGoogle Scholar
  8. 8.
    Marasco, W. A., and Becker, E. L., 1982, Anti-idiotype as antibody against the formyl peptide chemotaxis receptor of the neutrophil, J. Immunol. 128:963–968.PubMedGoogle Scholar
  9. 9.
    Wassermann, N. H., Penn, A. S., Freimuth, P. I., Treptow, N., Wentzel, S., Cleveland, W. L., and Erlanger, B. F., 1982, Anti-idiotypic route to anti-acetylcholine receptor antibodies and experimental myasthenia gravis, Proc. Natl. Acad. Sci. USA 79:4810–4814.PubMedGoogle Scholar
  10. 10.
    Cleveland, W. L., Wassermann, N. H., Sarangaran, R., Penn, A. S., and Erlanger, B. F., 1983, Monoclonal antibodies to the acetylcholine receptor (AChR) by a normally functioning auto-anti-idiotypic mechanism, Nature 305:56–57.PubMedGoogle Scholar
  11. 11.
    Schechter, Y., Marón, R., Elias, D., and Cohen, I. R., 1982, Autoantibodies to insulin receptor spontaneously develop as anti-idiotypes in mice immunized with insulin, Science 216:542–545.Google Scholar
  12. 12.
    Ubain, J., 1976, Idiotypes, expression of antibody diversity and network concepts, Ann. Immunol. (Inst. Pasteur) 127C: 357–374.Google Scholar
  13. 13.
    Cazenave, P.-A., 1977, Idiotypic anti-idiotypic regulation of antibody synthesis in rabbits, Proc. Natl. Acad. Sci. USA 74:5122–5125.PubMedGoogle Scholar
  14. 14.
    Sachs, D. H., Berzofsky, J. A., Pisetsky, D. S., and Schwartz, R. H., 1978, Genetic control of the immune response to staphylococcal nuclease, Springer Semin. Immunopathol. 1:51–83.Google Scholar
  15. 15.
    Wysocki, L. J., and Sato, V. L., 1981, The strain A anti-p-azophenylarsonate major cross-reactive idiotypic family includes members with no reactivity toward p-azophenylarsonate, Eur. J. Immunol. 11:832-839.PubMedGoogle Scholar
  16. 16.
    Armo, M., Mariame, B., Voegtle, D., and Cazenave, P.-A., 1982, The idiotypic network: The murine MOPC315 anti-DNP system, Ann. Immunol. (Inst. Pasteur) 133D:255–262.Google Scholar
  17. 17.
    Sachs, D. H., 1980, Genetic control of idiotype expression, in: Immunology 80 (M. Fougereau and J. Dausset, eds.), Academic Press, New York, pp. 478–495.Google Scholar
  18. 18.
    Cosenza, H., and Kohler, H., 1972, Specific suppression of the antibody response by antibodies to receptors, Proc. Natl. Acad. Sci. USA 69:2701–2705.PubMedGoogle Scholar
  19. 19.
    Hart, D. A., Wang, A. L., Pawlak, L. L., and Nisonoff, A., 1972, Suppression of idiotypic specificities in adult mice by administration of anti-idiotypic antibody, J. Exp. Med. 135:1293–1300.PubMedGoogle Scholar
  20. 20.
    Ju, S. T., Gray, A., and Nisonoff, A., 1977, Frequence of occurrence of idiotypes associated with anti-p- azophenylarsonate antibodies arising in mice immunologically suppressed with respect to a cross-reactive idiotype, J. Exp. Med. 145:549–556.Google Scholar
  21. 21.
    Bach, B. A., Greene, M. I., Benacerraf, B., and Nisonoff, A., 1979, Mechanisms of regulation of cell- mediated immunity. IV. Azobenzenearsonate-specific suppressor factor(s) bear cross-reactive idiotypic determinants the expression of which is linked to the heavy-chain allotype linkage group of genes,J. Exp. Med. 149:1084–1098.PubMedGoogle Scholar
  22. 22.
    Bona, C., Lieberman, R., House, S., Green, I., and Paul, W. E., 1979, Immune response to levan. II. T- independence of suppression of cross-reactive idiotypes by anti-idiotype antibodies, J. Immunol. 122:1614-1619.PubMedGoogle Scholar
  23. 23.
    Lynch, R. G., Graff, R. J., Sirisinha, S., Simms, E. S., and Eisen, H. N., 1972, Myeloma proteins as tumor-specific transplantation antigens, Proc. Natl. Acad. Sci. USA 69:1540–1544.PubMedGoogle Scholar
  24. 24.
    Jorgensen, T. O., 1982, Lymphocyte specificity for an isologous mouse myeloma protein, Thesis, Department of Immunology, Institute of Medical Biology, University of Tromso, Norway, pp. 1–41.Google Scholar
  25. 25.
    Eichmann, K., and Rajewsky, K., 1975, Induction of T and B cell immunity by anti-idiotypic antibody, Eur. J. Immunol. 5:661–666.PubMedGoogle Scholar
  26. 26.
    Miller, G. G. P., Nadler, P. I., Hodes, R. J., and Sachs, D. H., 1982, Modification of T cell antinuclease idiotype expression by in vivo administration of anti-idotype, J. Exp. Med. 155:190–200.PubMedGoogle Scholar
  27. 27.
    Oudin, J., and Cazenave, P.-A., 1971, Similar idiotypic specificities in immunoglobulin fractions with different antibody functions or even without detectable antibody function, Proc. Natl. Acad. Sci. USA 68:2616–2620.PubMedGoogle Scholar
  28. 28.
    Cazenave, P.-A., Ternynck, T., and Avrameas, S., 1974, Similar idiotypes in antibody-forming cells and in cells synthesizing immunoglobulins without detectable antibody function, Proc. Natl. Acad. Sci. USA 71:4500–4502.PubMedGoogle Scholar
  29. 29.
    Metzger, D. W., Miller, A., and Sercarz, E. E., 1980, Sharing of an idiotypic marker by monoclonal antibodies specific for distinct regions of hen lysozyme, Nature 287:540–542.PubMedGoogle Scholar
  30. 30.
    Kohno, Y., Berkower, I., Minna, J., and Berzofsky, J. A., 1982, Idiotypes of anti-myoglobin antibodies: Shared idiotypes among monoclonal antibodies to distinct determinants of sperm whale myoglobin, J. Immunol. 128:1742–1748.PubMedGoogle Scholar
  31. 31.
    Enghofer, E., Glaudemans, C. P. J., and Bosma, M. J., 1979, Immunoglobulins with different specificities have similar idiotypes, Mol. Immunol. 16:1103–1110.PubMedGoogle Scholar
  32. 32.
    Eichmann, K., Coutinho, A., and Melchers, F., 1977, Absolute frequencies of lipopolysaccharide-reactive B cells producing A5A idiotype in unprimed, streptococcal A carbohydrate-primed, anti-A5A idiotype- sensitized and anti-A5A idiotype-suppressed A/J mice,J. Exp. Med. 146:1436–1449.PubMedGoogle Scholar
  33. 33.
    Hiernaux, J., and Bona, C. A., 1982, Shared idiotypes among monoclonal antibodies specific for different immunodominant sugars oi lipopolysaccharide of different gram-negative bacteria, Proc. Natl. Acad. Sci. USA 79:1616–1620.PubMedGoogle Scholar
  34. 34.
    Sakato, N., Fujio, H., and Amano, T., 1980, Idiotypic analysis of antibodies to hen egg-white lysozyme (HEL). I. Occurrence of species-specific cross-reactive idiotypes of antibodies directed to distinct regions of HEL in guinea pigs, J. Immunol. 124:1866–1873.PubMedGoogle Scholar
  35. 35.
    Liu, Y., Bona, C. A., and Schulman, J. L., 1981, Idiotype of clonal responses to influenza virus hemagglutinin, J. Exp. Med. 154:1525–1538.PubMedGoogle Scholar
  36. 36.
    Ju, S.-T., Benacerraf, B., and Dorf, M. E., 1980, Genetic control of a shared idiotype among antibodies directed to distinct specificities, J.Exp. Med. 152:170–182.PubMedGoogle Scholar
  37. 37.
    Boyd, W. C., and Bernard, H., 1937, Quantitative changes in antibodies and globulin fraction in sera of rabbits injected with several antigens, J. Immunol. 33:111–122.Google Scholar
  38. 38.
    Rodkey, L. S., 1974, Studies on idiotypic antibodies: Production and characterization of autoantiidiotypic antisera, J. Exp. Med. 139:712–720.PubMedGoogle Scholar
  39. 39.
    Binion, S. B., and Rodkey, L. S., 1982, Naturally induced auto-anti-idiotypic antibodies: Induction by identical idiotopes in some members of an outbred rabbit family, J.Exp. Med. 156:860–872.PubMedGoogle Scholar
  40. 40.
    Rodkey, L. S., 1976, Studies of idiotypic antibodies: Reactions of isologous and autologous anti-idiotypic antibodies with the same antibody preparations, J.Immunol. 117:986–989.PubMedGoogle Scholar
  41. 41.
    Rodkey, L. S., 1980, Autoregulation of immune responses via idiotype network interactions, Microbiol. Rev. 44:631–659.PubMedGoogle Scholar
  42. 42.
    Kluskens, L. and Kohler, H., 1974, Regulation of immune response by autogeneous antibody against receptor, Proc. Natl. Acad. Sci. USA 71:5083–5087.PubMedGoogle Scholar
  43. 43.
    Bona, C. A., Heber-Katz, E., and Paul, W. E., 1981, Idiotype-anti-idiotype regulation. I. Immunization with a levan-binding myeloma protein leads to the appearance of auto-anti-(anti-idiotype) antibodies and to the activation of silent clones, J. Exp. Med. 153:951–967.PubMedGoogle Scholar
  44. 44.
    Kelsoe, G., and Cerny, J., 1979, Reciprocal expansions of idiotypic anti-idiotypic clones following antigen stimulation, Nature 279:333–334.PubMedGoogle Scholar
  45. 45.
    Schrater, A. F., Goidl, E. A., Thorbecke, J., and Siskind, G. W., 1979, Production of auto-anti-idiotypic antibody during the normal immune response to TNP-Ficoll. III. Absence in nu/nu mice: Evidence for T-cell dependence of the anti-idiotypic antibody response, J. Exp. Med. 150:808–817.PubMedGoogle Scholar
  46. 46.
    Jerne, N. K., 1974, Towards a network theory of the immune system, Ann. Immunol. (Inst. Pasteur) 125C:373–389.Google Scholar
  47. 47.
    Kunkel, H. G., Killander, J., and Mannik, M., 1966, Current trends in immune globulin research, Acta Med. Scand. Suppl. 445:63–73.PubMedGoogle Scholar
  48. 48.
    Lieberman, R., Potter, M., Humphrey, W., Jr., Mushinski, E. B., and Vrana, M., 1975, Multiple individual and cross-specific idiotypes on 13 levan-binding myeloma proteins of BALB/c mice, J.Exp. Med. 142:106–119.PubMedGoogle Scholar
  49. 49.
    Kunkel, H. G., Agnello, V., Joslin, F. G., Winchester, R. J., and Capra, J. D., 1973, Cross idiotypic specificity among monoclonal IgM proteins with anti-γ-globulin activity, J. Exp. Med. 137:331–342.PubMedGoogle Scholar
  50. 50.
    Agnello, V., Arbetter, A., Ibanez de Kasep, G., Powell, R., Tan, E. M., and Joslin, F., 1980. Evidence for a subset of rheumatoid factors that cross-react with DNA-histone and have a distinct cross-idiotype, J. Exp. Med. 151:1514–1527.PubMedGoogle Scholar
  51. 51.
    Riesen, W. F., Braun, D. G., Škvǎril, F., and Mansa, B., 1982, Idiotypic and structural analysis of monoclonal human immunoglobulins with anti-streptolysin O activity, Int. Arch. Allergy Appl. Immunol. 67:86–92.PubMedGoogle Scholar
  52. 52.
    Abraham, G. N., Podell, D. N., Welch, E. H., and Johnston, S. L., 1983, Idiotypic relatedness of human monoclonal IgG cryoglobulins, Immunology 48:315–320.PubMedGoogle Scholar
  53. 53.
    Feizi, T., Kunkel, H. G., and Roelcke, D., 1974, Cross idiotypic specificity among cold agglutinins in relation to combining activity for blood group-related antigens, Clin. Exp. Immunol. 18:283–293.PubMedGoogle Scholar
  54. 54.
    Pillemer, E., and Weissman, I. L., 1981, A monoclonal antibody that detected a VK-TEPC15 idiotypic determinant cross-reactive with a Thy-1 determinant, J. Exp. Med. 153:1068–1079.PubMedGoogle Scholar
  55. 55.
    Riesen, W. F., 1979, Idiotypic cross-reactivity of human and murine phosphorylcholine-binding immunoglobulins, Eur. J. Immunol. 9:421–425.PubMedGoogle Scholar
  56. 56.
    Karol, R. A., Reichlin, M., and Nobel, R. W., 1977, Evolution of an idiotypic determinant: Anti-Val, J. Exp. Med. 146:435–444.PubMedGoogle Scholar
  57. 57.
    Jackson, S., Kulhavy, R., and Mestecky, J., 1981, Shared idiotypes among anti-albumin antibodies of different species, Scand. J. Immunol. 14:31–37.PubMedGoogle Scholar
  58. 58.
    Young, N. M., and Williams, R. E., 1978, Comparison of the secondary structures and binding sites of C-reactive protein and the phosphorylcholine-binding murine myeloma proteins, J. Immunol. 121:1893–1898.PubMedGoogle Scholar
  59. 59.
    Volanakis, J. E., and Kearney, J. F., 1981, Cross-reactivity between C-reactive protein and idiotypic determinants on a phosphocholine-binding murine myeloma protein, J.Exp. Med. 153:1604–1614.PubMedGoogle Scholar
  60. 60.
    Kabat, E. A., Wu, T. T., and Bilofsky, H., 1976, Attempts to locate residues in complementarity-determining regions of antibody combining sites that make contact with antigen, Proc. Natl. Acad. Sci. USA 73:617–619.PubMedGoogle Scholar
  61. 61.
    Kabat, E. A., 1978, The structural basis of antibody complementarity,Adv. Protein Chem. 32:1–75.PubMedGoogle Scholar
  62. 62.
    Kabat, E. A., Wu, T. T., Bilofsky, H., Reid-Miller, M., and Perry, H., 1983,Sequences of Proteins of Immunological Interest Tabulation and analysis of amino acid and nucleic acid sequences of precursors, V-regions, G-regions, J-chain, β2-microglobulins, major histocompatibility antigens, Thy-1, complement, C-reactive protein, thymopoietin, post-gamma globulin, and α2-macroglobulin, National Institutes of Health, Bethesda.Google Scholar
  63. 63.
    Childs, R., and Feizi, T., 1975, Cross idiotypic specificity among heavy chains of macroglobulins with blood group I and i specificities, Nature 255:562–564.PubMedGoogle Scholar
  64. 64.
    Milner, E. C. B., and Capra, J. D., 1983, Structural analysis of monoclonal anti-arsonate antibodies: Idiotypic specificities are determined by the heavy chain,Mol. Immunol. 20:39–46.PubMedGoogle Scholar
  65. 65.
    Lieberman, R., Vrana, M., Humphrey, W., Chien, C. C., and Potter, M., 1977, Idiotypes of inulin- binding myeloma proteins localized to variable region light and heavy chains: Genetic significance, J. Exp. Med. 146:1294–1304.PubMedGoogle Scholar
  66. 66.
    Nahm, M. H., Clevinger, B. L., and Davie, J. M., 1982, Monoclonal antibodies to streptococcal group A carbohydrates. I. A dominant idiotypic determinant is located in Vx, J. Immunol. 129:1513–1518.PubMedGoogle Scholar
  67. 67.
    Sogn, J. A., Yarmush, M. L., and Kindt, T. J., 1976, An idiotypic marker for the VL region of an homogeneous antibody, Ann. Immunol. (Inst. Pasteur) 127C:397–408.Google Scholar
  68. 68.
    Yarmush, M., Sogn, J. A., Mudgett, M., and Kindt, T. J., 1977, The inheritance of antibody V regions in the rabbit: Linkage of an H-chain-specific idiotype to immunoglobulin allotypes, J. Exp. Med. 145:916–930.PubMedGoogle Scholar
  69. 69.
    Kaartinen, M., Griffiths, G. M., Hamlyn, P. H., Markham, A. F., Karjalainen, K., Pelkonen, J. L. T., Makela, O., and Milstein, C., 1983, Anti-oxazolone hybridomas and the structure of the oxazolone idiotype, J. Immunol. 130:937–945.PubMedGoogle Scholar
  70. 70.
    Schiff, C., Boyer, C., Milili, M., and Fougereau, M., 1979, The idiotypy of the MOPC 173 (IgG2a) mouse myeloma protein: Characterization of syngeneic, allogeneic and xenogeneic anti-idiotypic antibodies. Contribution of the H and L chains to the idiotypic determinants, Eur. J. Immunol. 9:831–841.PubMedGoogle Scholar
  71. 71.
    Brown, A. R., Gottlieb, P. D., and Nisonoff, A., 1981, Role and strain distribution of genes controlling light chains needed for the expression of an intrastrain cross-reactive idiotype, Immunogenetics 14:85–99.PubMedGoogle Scholar
  72. 72.
    Somme, G., Sera, J. R., Leclercq, L., Moreau, J.-L., Mazie, J.-C., Moinier, D., Fugereau, M., and Theze, J., 1982, Contribution of the H- and L-chains and of the binding site to the idiotypic specificities of mouse anti-GAT antibodies, Mol. Immunol 19:1011–1019.PubMedGoogle Scholar
  73. 73.
    Misaki, A., Torii, M., Sawai, T., and Goldstein, I. J., 1980, Structure of the dextran of Leuconostoc mesenteroides B-1355,Carbohydr. Res. 84:273–285.Google Scholar
  74. 74.
    Seymour, F., Knapp, R. D., Chen, E. C. M., Bishop, S. H., and Jeanes, A., 1979, Structural analysis of Leuconostoc dextrans containing 3-O-α-D-glucosylated α-D-glucosyl residues in both linear-chain and branch-point positions or only in branch-point positions by methylation and by 13C-NMR spectroscopy, Carbohydr. Res. 74:41–62.Google Scholar
  75. 75.
    Sidebotham, R. L.1974, Dextrans, Adv. Carbohydr. Chem. Biochem. 30:371–444.PubMedGoogle Scholar
  76. 76.
    Jeanes, A., Haynes, W. C., Wilham, C. A., Rankin, J. C., Melvin, E. H., Austin, M. J., Cluskey, J. E., Fisher, B. E., Tsuchiya, H. M., and Rist, C. E., 1954, Characterization and classification of dextrans from ninety-six strains of bacteria,J. Am. Chem. Soc. 76:5041–5052.Google Scholar
  77. 77.
    Jeanes, A., and Seymour, F., 1979, The a-D-glucopyranosidic linkages of dextrans: Comparison of percentages from structural analysis by peridoate oxidation and by methylation,Carbohydr. Res. 74:31–40.Google Scholar
  78. 78.
    Schilling, J., Clevinger, B., Davie, J. M., and Hood, L., 1980, Amino acid sequence of homogeneous antibodies to dextran and DNA rearrangements in heavy chain V-region gene segments, Nature 283:35–40.PubMedGoogle Scholar
  79. 79.
    Clevinger, B., Schilling, J., Hood, L., and Davie, J. M., 1980, Structural correlates of cross-reactive and individual idiotypic determinants on murine antibodies to α-(1→3) dextran, J. Exp. Med. 151:1059–1070.PubMedGoogle Scholar
  80. 80.
    Kehry, M., Sibley, L., Fuhrman, J., Schilling, J., and Hood, L., 1979, Amino acid sequence of a mouse immunoglobulin µ chain, Proc. Natl. Acad. Sci. USA 76:2932–2936.PubMedGoogle Scholar
  81. 81.
    Newman, B., Sugii, S., Kabat, E. A., Torii, M., Clevinger, B. L., Schilling, J., Bond, M., Davie, J. M., and Hood, L., 1983, Combining site specificities of mouse hybridoma antibodies to dextran B1355S, J. Exp. Med. 157:130–140.PubMedGoogle Scholar
  82. 82.
    Kabat, E. A., Wu, T. T., and Bilofsky, H., 1978, Variable region genes for the immunoglobulin framework are assembled from small segments of DNA—A hypothesis, Proc. Natl. Acad. Sci. USA 75:2429–2433.PubMedGoogle Scholar
  83. 83.
    Weigert, M., Gatmaitan, L., Loh, E., Schilling, J., and Hood, L., 1978, Rearrangement of genetic information may produce immunoglobulin diversity, Nature 276:785–790.PubMedGoogle Scholar
  84. 84.
    Valbuena, O., Marcu, K. B., Weigert, M., and Perry, R. P., 1978, Multiplicity of germline genes specifying a group of related mouse K chains with implications for the generation of immunoglobulin diversity, Nature 276:780–784.PubMedGoogle Scholar
  85. 85.
    Kabat, E. A., Wu, T. T., and Bilofsky, H., 1979, Evidence supporting somatic assembly of the DNA segments (minigenes), coding for the framework, and complementarity determining segments of immunoglobulin variable regions, J. Exp. Med. 149:1299–1313.PubMedGoogle Scholar
  86. 86.
    Wu, T. T., Kabat, E. A., and Bilofsky, H., 1979, Some sequence similarities among mouse DNA segments that code for λ and K light chains of immunoglobulins,Proc. Natl. Acad. Sci. USA 76:4617–4621.PubMedGoogle Scholar
  87. 87.
    Kabat, E. A., Wu, T. T., and Bilofsky, H., 1980, Evidence indicating independent assortment of framework and complementarity-determining segments of the variable regions of rabbit light chains: Delineation of a possible J minigene, J. Exp. Med. 152:72–84.PubMedGoogle Scholar
  88. 88.
    Kabat, E. A., 1980, Antibodies, hypervariable regions and minigenes, J. Immunol. 125:961–969.PubMedGoogle Scholar
  89. 89.
    Kabat, E. A., 1982, Antibody diversity versus antibody complementarity,Pharmacol. Rev. 34:23–38.PubMedGoogle Scholar
  90. 90.
    Juszczak, E. C., and Margolies, M., 1983, Amino acid sequence of the heavy chain variable regions of the A/J mouse anti-arsonate monoclonal antibody 36/60 bearing a minor idiotype, Biochemistry 22: 4291–4296.PubMedGoogle Scholar
  91. 91.
    Wood, C., and Tonegawa, S., 1983, Diversity and joining segments of mouse immunoglobulin heavy chain genes are closely linked and in the same orientation: Implications for the joining mechanism, Proc. Natl. Acad. Sci. USA 80:3030–3034.PubMedGoogle Scholar
  92. 92.
    Wu, T. T., and Kabat, E. A., 1982, Fourteen nucleotides in the second complementarity-determining region of a human heavy-chain variable region gene are identical with a sequence in a human D minigene, Proc. Natl. Acad. Sci. USA 79:5031–5032.PubMedGoogle Scholar
  93. 93.
    Rechavi, G., Ram, D., Glazer, L., Zakut, R., and Givol, D., 1983, Evolutionary aspects of immunoglobulin heavy chain variable regions (V H) gene subgroups, Proc. Natl. Acad. Sci. USA 80:855–859.PubMedGoogle Scholar
  94. 94.
    Bernstein, K. E., Reddy, E. P., Alexander, C. B., and Mage, R. G., 1982. A cDNA sequence encoding a rabbit heavy chain variable region of the VHa2 allotype showing homologies with human heavy chain sequences, Nature 300:74–76.PubMedGoogle Scholar
  95. 95.
    Siebenlist, U., Ravetch, J. V., Korsmeyer, S., Waldmann, T., and Leder, P, 1981, Human immunoglobulin D segments encoded in tandem multigenic families, Nature 294:631–635.PubMedGoogle Scholar
  96. 96.
    Takahashi, N., Noma, T., and Honjo, T., 1984, Rearranged immunoglobulin VH pseudogene that deletes the second complementarity determining region Proc. Natl. Acad. Sci. USA 81: (in press).Google Scholar
  97. 97.
    Alt, F. W., and Baltimore, D., 1982, Joining of immunoglobulin heavy chain gene segments: Implications from a chromosome with evidence of three D-JH fusions, Proc. Natl. Acad. Sci. USA 79:4118–4122.PubMedGoogle Scholar
  98. 98.
    Dreher, K. L., Emorine, L., Kindt, T. J., and Max, E. E., 1983, A cDNA clone encoding a complete rabbit immunoglobulin K light chain of b4 allotype,Proc. Natl. Acad. Sci. USA 80:4489–4493.PubMedGoogle Scholar
  99. 99.
    Eulitz, M., and Linke, R. P., 1982, Primary structure of the variable part of an amyloidogenic Bence- Jones protein (Mev.): An unusual insertion in the third hypervariable region of a human k-immunoglobulin light chain, Hoppe-Seylers Z. Physiol. Chem. 363S:1347–1358.Google Scholar
  100. 100.
    Potter, M., 1977, Antigen binding myeloma proteins of mice, in: Advances of Immunology Vol 25 (H. G. Kunkel and F. J. Dixon, eds.), Academic Press, New York, pp. 141–211.Google Scholar
  101. 101.
    Sharon, J., D’Hoostelaere, L., Potter, M., Kabat, E. A., and Morrison, S. L., 1982, A cross-reactive idiotype, QUPC52 IdX, present on most but not all anti-α(1→6) dextran-specific IgM and IgA hybridoma antibodies with combining sites of different sizes, J. Immunol: 128:498–500.PubMedGoogle Scholar
  102. 102.
    Cisar, J., Kabat, E. A., Dorner, M., and Liao, J., 1975, Binding properties of immunoglobulin combining sites specific for terminal or non-terminal antigenic determinants in dextran, J. Exp. Med. 142:435–459.PubMedGoogle Scholar
  103. 103.
    Sharon, J., Kabat, E. A., and Morrison, S. L., 1982, Immunochemical characterization of binding sites of hybridoma antibodies specific for α(1→6) linked dextran, Mol. Immunol. 19:375–388.PubMedGoogle Scholar
  104. 104.
    Margolies, M. N., Wysocki, L. J., and Sato, V. L., 1983, Immunoglobulin idiotype and anti-anti-idiotype utilize the same variable region genes irrespective of antigen specificity, J. Immunol. 130:515–517.PubMedGoogle Scholar
  105. 105.
    Dickerman, J., Clevinger, B., and Friedenson, B., 1981, Loss of an individual idiotype on chemical modification: A strategy for assigning idiotypic determinants, J. Exp. Med. 153:1275–1285.PubMedGoogle Scholar
  106. 106.
    Segal, D. M., Padlan, E. A., Cohen, G. H., Rudikoff, S., Potter, M., and Davies, D. R., 1974, The three- dimensional structure of a phosphorylcholine-binding mouse immunoglobulin Fab and the nature of the antigen binding site, Proc. Natl. Acad. Sci. USA 71:4298–4302.PubMedGoogle Scholar
  107. 107.
    Saul, F. A., Amzel, L. M., and Poljak, R. J., 1978, Preliminary refinement and structural analysis of the Fab fragment from human immunoglobulin New at 2 Å resolution, J. Biol. Chem. 253:585–595.PubMedGoogle Scholar
  108. 108.
    Sigal, N. H., 1977, Novel idiotypic and antigen-binding characteristics in two anti-dinitrophenyl monoclonal antibodies, J. Exp. Med. 146:282–286.PubMedGoogle Scholar
  109. 109.
    Schiff, C., Boyer, C., Milili, M., and Fougereau, M., 1981, Structural basis for M-173 idiotypic determinants distinctively recognized in syngeneic and allogeneic immunization: Contribution of DH, JH and Jk regions to an idiotope recognized by allogeneic antisera, Ann. Immunol. (Inst. Pasteur) 132C:113–129.Google Scholar
  110. 110.
    Johnson, N., Slankard, J., Paul, L., and Hood, L., 1982, The complete V domain amino acid sequences of two myeloma inulin-binding proteins,J. Immunol. 128:302–307.PubMedGoogle Scholar
  111. 111.
    Rudikoff, S., Pawlita, M., Pumphrey, J., Mushinski, E., and Potter, M., 1983, Galactan binding antibodies: Diversity and structure of idiotypes, J. Exp. Med. 158:1385–1400.PubMedGoogle Scholar
  112. 112.
    Rudikoff, S., 1983, Immunoglobulin structure-function correlates: Antigen binding and idiotypes, in: Contemporary Topics in Molecular Immunology Vol. 9 (F. P. Inman and T. J. Kindt, eds.), Plenum Press, New York, pp. 169–209.Google Scholar
  113. 113.
    Pawlita, M., Mushinski, E., Feldmann, R. J., and Potter, M., 1981, A monoclonal antibody that defines an idiotope with two subsites in galactan-binding myeloma proteins, J. Exp. Med. 154:1946–1956.PubMedGoogle Scholar
  114. 114.
    Rajewski, K., and Takemori, T., 1983, Genetic expression and function of idiotypes, in: Annual Review of Immunology Vol. 1 (W. E. Paul, C. G. Fathman, and H. Metzger, eds.), Annual Reviews, Inc., Palo Alto, pp. 569–607.Google Scholar
  115. 115.
    Dildrop, R., Bruggemann, M., Radbruch, A., Rajewsky, K., and Beyreuther, K., 1982, Immunoglobulin V region variants in hybridoma cells. II. Recombination between V genes, EMBO J. 1:635–640.PubMedGoogle Scholar
  116. 116.
    Marchalonis, J. J., Wang, A.-C., and Wu, T. T., 1983, Identification of amino acid residues implicated in the cross-reaction between immunoglobulin VH and a T cell receptor molecule, Exp. and Clinical Immunogenetics 1: (in press).Google Scholar
  117. 117.
    Segal, D. M., Padlan, E. A., Cohen, G. H., Rudikoff, S., Potter, M., and Davies, D. R., 1974, The three- dimensional structure of a phosphorylcholine-binding mouse immunoglobulin Fab and the nature of the antigen binding site, Proc. Natl. Acad. Sci. USA 71:4298–4302.PubMedGoogle Scholar
  118. 118.
    Saul, F. A., Amzel, L. M., and Poljak, R. J., 1978, Preliminary refinement and structural analysis of the Fab fragment from human immunoglobulin New at 2 Å resolution, J. Biol. Chem. 253:585–595.PubMedGoogle Scholar
  119. 119.
    Marquart, M., Deisenhofer, J., Huber, R., and Palm, W., 1980, Crystallographic refinement and atomic models of the intact immunoglobulin molecule Kol and its antigen-binding fragment at 3.0 Å and 1.9 Å resolution, J. Mol. Biol. 141:369–391.PubMedGoogle Scholar
  120. 120.
    Marquart, M., and Deisenhofer, J., 1983, The three-dimensional structure of antibodies, Immunol. Today 3:160–166.Google Scholar
  121. 121.
    Davies, D. R., and Padlan, E. A., 1977, Correlations between antigen-binding specificity and the three- dimensional structure of the antibody combining sites, in: Antibodies in Human Diagnosis and Therapy (E. Haber and R. M. Krause, eds.), Raven Press, New York, pp. 119–143.Google Scholar
  122. 122.
    Davies, D. R., and Metzger, H., 1983, Structural basis of antibody function, in: Annual Review of Immunology Vol. 1 (W. E. Paul, C. G. Fathman, and H. Metzger, eds.), Annual Reviews, Inc., Palo Alto, pp. 87–117.Google Scholar
  123. 123.
    Mage, R. G., and Kabat, E. A., 1963, The combining regions of the type III pneumococcus polysaccharide and homologous antibody, Biochemistry 2:1278–1288.PubMedGoogle Scholar
  124. 124.
    Bennett, L. G., and Glaudemans, C. P. J., 1979, The affinity of a linear, α-D-(1→6)-linked D-glucopyranan (dextran) for homogeneous immunoglobulin A W3129, Carbohydr. Res. 72:315–319.PubMedGoogle Scholar
  125. 125.
    Weigert, M., Raschke, W. C., Carson, D., and Cohn, M., 1974, Immunochemical analysis of the idiotypes of mouse myeloma proteins with specificity for levan or dextran, J. Exp. Med. 139:137–147.PubMedGoogle Scholar
  126. 126.
    Ekborg, G., Ittah, Y., and Glaudemans, C. P. J., 1983, Monoclonal IgA J539 binds galactopyranosyl antigens on its surface, Mol. Immunol. 20:235–238.PubMedGoogle Scholar
  127. 127.
    Morahan, G., Berek, C., and Miller, J. F. A. P., 1983, An idiotypic determinant formed by both immunoglobulin constant and variable regions, Nature 301:720–722.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Elvin A. Kabat
    • 1
    • 2
  1. 1.Departments of Microbiology, Human Genetics and Development, and Neurology, and Cancer Center/Institute for Cancer ResearchColumbia University College of Physicians and SurgeonsNew YorkUSA
  2. 2.National Institute of Allergy and Infectious DiseasesNational Institutes of HealthBethesdaUSA

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