Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1976 May;73(5):1702–1706. doi: 10.1073/pnas.73.5.1702

Demonstration of an idiotypic antigen on a monoclonal cold agglutinin and on its isolated heavy and light chains.

L Kobzik, M C Brown, A G Cooper
PMCID: PMC430368  PMID: 58418

Abstract

A potent anti-idiotype serum produced in a rabbit immunized with the isolated heavy chains of an IgM cold agglutinin "Col" was rendered specific by solid-state adsorptions. The anit-Col idiotype was shown to bind specifically to both isolated Col heavy (mu) and light (kappa) chains as well as to intact Col IgM by three methods: (i) reversal of anti-idiotype inhibition of Col cold agglutinin in an automated hemagglutination-inhibition assay system; (ii) adsorption of the anti-idiotype by affinity gels consisting of Col IgM, mu, or kappa chains covalently coupled to Sepharose 2B; (iii) binding of Col IgM and its isolated chains by an anti-idiotype affinity gel. Fragments of Col light chain lacking constant region determinants but still capable of inhibiting anti-idiotype were produced by limited pepsin digestion of the light chains. The finding of shared idiotypic determinants on isolated heavy and light chains of a monoclonal antibody suggests that these chains share a common sequence in a hypervariable region. As an extension of the gene insertion theory of Wu and Kabat, we postulate that genes coding for hypervariable regions may be available for insertion into the DNA for both heavy and light chains.

Full text

PDF

Images in this article

1703Image
on p.1703

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brient B. W., Nisonoff A. Quantitative investigations of idiotypic antibodies. IV. Inhibition by specific haptens of the reaction of anti-hapten antibody with its anti-idiotypic antibody. J Exp Med. 1970 Nov;132(5):951–962. doi: 10.1084/jem.132.5.951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Capra J. D., Kehoe J. M. Hypervariable regions, idiotypy, and the antibody-combining site. Adv Immunol. 1975;20:1–40. doi: 10.1016/s0065-2776(08)60205-9. [DOI] [PubMed] [Google Scholar]
  3. Capra J. D., Kehoe J. M. Structure of antibodies with shared idiotypy: the complete sequence of the heavy chain variable regions of two immunoglobulin M anti-gamma globulins. Proc Natl Acad Sci U S A. 1974 Oct;71(10):4032–4036. doi: 10.1073/pnas.71.10.4032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cazenave P. A., Ternynck T., Avrameas S. Similar idiotypes in antibody-forming cells and in cells synthesizing immunoglobulins without detectable antibody function. Proc Natl Acad Sci U S A. 1974 Nov;71(11):4500–4502. doi: 10.1073/pnas.71.11.4500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Claflin J. L., Davie J. M. Clonal nature of the immune response to phosphorylcholine (PC). V. Cross-idiotypic specificity among heavy chains of murine anti-PC antibodies and PC-binding myeloma proteins. J Exp Med. 1975 May 1;141(5):1073–1083. doi: 10.1084/jem.141.5.1073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cohen S., Cooper A. G. Chemical differences between individual human cold agglutinins. Immunology. 1968 Jul;15(1):93–100. [PMC free article] [PubMed] [Google Scholar]
  7. Cooper A. G., Brown M. C., Derby H. A., Wortis H. H. Quantitation of surface-membrane and intracellular gamma, mu and kappa chains of normal and neoplastic human lymphocytes. Clin Exp Immunol. 1973 Apr;13(4):487–496. [PMC free article] [PubMed] [Google Scholar]
  8. Cooper A. G., Brown M. C. Serum i antigen: a new human blood-group glycoprotein. Biochem Biophys Res Commun. 1973 Nov 16;55(2):297–304. doi: 10.1016/0006-291x(73)91087-5. [DOI] [PubMed] [Google Scholar]
  9. Cooper A. G., Chavin S. I., Franklin E. C. Predominance of a single mu chain subclass in cold agglutinin heavy chains. Immunochemistry. 1970 May;7(5):479–483. doi: 10.1016/0019-2791(70)90230-2. [DOI] [PubMed] [Google Scholar]
  10. Cooper A. G. Hemagglutinating 7S subunits of 19S cold agglutinins. Science. 1967 Aug 25;157(3791):933–935. doi: 10.1126/science.157.3791.933. [DOI] [PubMed] [Google Scholar]
  11. Cooper A. G., Hobbs J. R. Immunoglobulins in chronic cold haemagglutinin disease. Br J Haematol. 1970 Sep;19(3):383–396. doi: 10.1111/j.1365-2141.1970.tb01635.x. [DOI] [PubMed] [Google Scholar]
  12. Cooper A. G. Purification of cold agglutinins from patients with chronic cold haemagglutinin disease. Evidence of their homogeneity from starch gel electrophoresis of isolated light chains. Clin Exp Immunol. 1968 Sep;3(7):691–702. [PMC free article] [PubMed] [Google Scholar]
  13. FAHEY J. L., HORBETT A. P. Human gamma globulin fractionation on anion exchange cellulose columns. J Biol Chem. 1959 Oct;234:2645–2651. [PubMed] [Google Scholar]
  14. FLEISCHMAN J. B., PORTER R. R., PRESS E. M. THE ARRANGEMENT OF THE PEPTIDE CHAINS IN GAMMA-GLOBULIN. Biochem J. 1963 Aug;88:220–228. doi: 10.1042/bj0880220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fairbanks G., Steck T. L., Wallach D. F. Electrophoretic analysis of the major polypeptides of the human erythrocyte membrane. Biochemistry. 1971 Jun 22;10(13):2606–2617. doi: 10.1021/bi00789a030. [DOI] [PubMed] [Google Scholar]
  16. Feizi T., Kunkel H. G., Roelcke D. Cross idiotypic specificity among cold agglutinins in relation to combining activity for blood group-related antigens. Clin Exp Immunol. 1974 Oct;18(2):283–293. [PMC free article] [PubMed] [Google Scholar]
  17. Franklin E. C., Frangione B. Two serologically distinguishable subclasses of mu-chains of human macroglobulins. J Immunol. 1967 Oct;99(4):810–814. [PubMed] [Google Scholar]
  18. Hopper J. E. Comparative studies on monotypic IgMlambda and IgGkappa from an individual patient. I. Evidence for shared VH idiotypic determinants. J Immunol. 1975 Oct;115(4):1101–1107. [PubMed] [Google Scholar]
  19. Huser H., Haimovich J., Jaton J. C. Antigen binding and idiotypic properties of reconstituted immunoglobulins G derived from homogeneous rabbit anti-pneumococcal antibodies. Eur J Immunol. 1975 Mar;5(3):206–210. doi: 10.1002/eji.1830050311. [DOI] [PubMed] [Google Scholar]
  20. Kindt T. J., Klapper D. G., Waterfield M. D. An idiotypic cross-reaction between allotype a3 and allotype a negative rabbit antibodies to streptococcal carbohydrate. J Exp Med. 1973 Mar 1;137(3):636–648. doi: 10.1084/jem.137.3.636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kluskens L., Lee W., Köhler H. Immune response to phosphorylcholine. I. Characterization of the epitope-specific antibody. Eur J Immunol. 1976 Jul;5(7):489–496. doi: 10.1002/eji.1830050712. [DOI] [PubMed] [Google Scholar]
  22. Kunkel H. G., Agnello V., Joslin F. G., Winchester R. J., Capra J. D. Cross-idiotypic specificity among monoclonal IgM proteins with anti- -globulin activity. J Exp Med. 1973 Feb 1;137(2):331–342. doi: 10.1084/jem.137.2.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Miller F., Metzger H. Characterization of a human macroglobulin. II. Distribution of the disulfide bonds. J Biol Chem. 1965 Dec;240(12):4740–4745. [PubMed] [Google Scholar]
  24. Porath J., Axen R., Ernback S. Chemical coupling of proteins to agarose. Nature. 1967 Sep 30;215(5109):1491–1492. doi: 10.1038/2151491a0. [DOI] [PubMed] [Google Scholar]
  25. Schneider M., Hilschmann N. Die Primärstruktur einer monoklonalen Immunglobulin-L-Kette der Subgruppe IV vom kappa-Typ (Bence-Jones-Protein Len.): eine neue Subgruppe der L-Ketten vom kappa-Typ. Hoppe Seylers Z Physiol Chem. 1974 Sep;355(9):1164–1168. [PubMed] [Google Scholar]
  26. Seon B. K., Roholt O. A., Pressman D. A simple efficient procedure for the preparation of fragments corresponding to the variable-half and constant-half portions of Bence Jones protein. J Immunol. 1972 Dec;109(6):1201–1209. [PubMed] [Google Scholar]
  27. Sher A., Cohn M. Inheritance of an idiotype associated with the immune response of inbred mice to phosphorylcholine. Eur J Immunol. 1972 Aug;2(4):319–326. doi: 10.1002/eji.1830020405. [DOI] [PubMed] [Google Scholar]
  28. Sirisinha S., Eisen H. N. Autoimmune-like antibodies to the ligand-binding sites of myeloma proteins. Proc Natl Acad Sci U S A. 1971 Dec;68(12):3130–3135. doi: 10.1073/pnas.68.12.3130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Thunberg A. L., Kindt T. J. An idiotypic cross-reaction between two streptococcal antibodies from an individual rabbit. Eur J Immunol. 1974 Jul;4(7):478–483. doi: 10.1002/eji.1830040707. [DOI] [PubMed] [Google Scholar]
  30. Urbain J., Tasiaux N., Leuwenkroon R., Van Acker A., Mariame B. Sharing of idiotypic specificities between different antibody populations from an individual rabbit. Eur J Immunol. 1975 Aug;5(8):570–575. doi: 10.1002/eji.1830050813. [DOI] [PubMed] [Google Scholar]
  31. Wang A. C., Fudenberg H. H., Wells J. V. A new subgroup of the Kappa chain variable region associated with anti-Pr cold agglutinins. Nat New Biol. 1973 May 23;243(125):126–128. [PubMed] [Google Scholar]
  32. Wells J. V., Fudenberg H. H., Givol D. Localization of idiotypic antigenic determinants in the Fv region of murine myeloma protein MOPC-315. Proc Natl Acad Sci U S A. 1973 May;70(5):1585–1587. doi: 10.1073/pnas.70.5.1585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Willims R. C., Jr, Kunkel H. G., Capra J. D. Antigenic specificities related to the cold agglutinin activity of gamma M globulins. Science. 1968 Jul 26;161(3839):379–381. doi: 10.1126/science.161.3839.379. [DOI] [PubMed] [Google Scholar]
  34. Wilson L. A., Amos D. B. Subcellular location of HL-A antigens. Tissue Antigens. 1972;2(2):105–111. doi: 10.1111/j.1399-0039.1972.tb00124.x. [DOI] [PubMed] [Google Scholar]
  35. Wu T. T., Kabat E. A. An analysis of the sequences of the variable regions of Bence Jones proteins and myeloma light chains and their implications for antibody complementarity. J Exp Med. 1970 Aug 1;132(2):211–250. doi: 10.1084/jem.132.2.211. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES