The Use of Hybridoma Antibodies to Probe the Antigenic Determinants of Thyroglobulin

  • N. R. Rose
  • M. Accavitti
  • E. F. Pydyn
  • M. A. Leon
  • R. K. Brown
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 150)


Experimental autoimmune thyroiditis has provided a fruitful model for the study of human autoimmune disease and for deepening our understanding of the mechanisms of self-non-self discriminationl. The disease is produced by injection of mice (or other experimental animals) with crude mouse thyroid extract or purified mouse thyroglobulin (MTg) together with a suitable adjuvant. Injection of complete Freund’s adjuvant (CFA) with MTg elicits production of autoantibodies to thyroglobulin and infiltration of the thyroid gland by lymphocytes, macrophages and other mononuclear cells; i.e., chronic thyroiditis is produced. Injection of large doses of MTg without adjuvant renders mice unresponsive to MTg, due to production of MTg-specific suppressor T cells9. Immunization with Tg under diverse conditions, therefore, may lead to autoantibodies alone, to both autoantibodies and thyroid lesions, or to suppression.


High Pressure Liquid Chromatography Antigenic Determinant Autoimmune Thyroiditis Good Responder Chronic Thyroiditis 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    N. R. Rose, L. D. Bacon, R. S. Sundick, Y. M. Kong, P. S. Esquivel and P. E. Bigazzi, Genetic regulation in autoimmune thyroiditis, in: “Autoimmunity: Genetic, Immunologic, Virologic, and Clinical Aspects,” N. Talal, ed., Academic Press, New York (1977).Google Scholar
  2. 2.
    A. 0. Vladutiu, and N. R. Rose, Autoimmune murine thyroiditis: Relation to histocompatibility (H-2) type, Science 174: 1137 (1971).Google Scholar
  3. 3.
    Y. M. Kong, C. S. David, A. A. Giraldo, M. ElRehewy and N. R. Rose, Fine structure of genetic control of autoimmune response to mouse thyroglobulin, in: “Genetic Control of Autoimmune Disease,” N. R. Rose, P. E. Bigazzi and N. L. Warner, eds., Elsevier/North-Holland, New York (1978).Google Scholar
  4. 4.
    P. S. Esquivel, N. R. Rose and Y. M. Kong, Induction of auto-immunity in good, and poor responder mice with mouse thyroglobulin and lipopolysaccharide, J. Exp. Med. 145: 1250 (1977).PubMedCrossRefGoogle Scholar
  5. 5.
    V. Tomazic and N. R. Rose, Autoimmune murine thyroiditis. VIII. Role of different thyroid antigens in the induction of experimental autoimmune thyroiditis, Immunology 30: 63 (1976).PubMedGoogle Scholar
  6. 6.
    V. Tomazic, N. R. Rose, and D. C. Shreffler, Autoimmune murine thyroiditis. IV. Localization of genetic control of the immune response, J. Immunol. 112: 965 (1974).PubMedGoogle Scholar
  7. 7.
    K. W. Beisel, C. S. David, A. A. Giraldo, Y. M. Kong, and N. R, Rose, Regulation of experimental autoimmune thyroiditis: Mapping of susceptibility to the I-A subregion of the mouse H-2, submitted (1981).Google Scholar
  8. 8.
    Y. M. Kong, C. S. David, A. A. Giraldo, M. ElRehewy and N. R. Rose, Regulation of autoimmune response to mouse thyroglobulin: Influence of H-2D-end genes, J. Immunol. 123: 15 (1979).PubMedGoogle Scholar
  9. 9.
    N. R. Rose, Y. M. Kong, I. Okayasu, A. A. Giraldo, K. Beisel and R. Sundick, T-cell regulation in autoimmune thyroiditis, Immunol. Rev. 55: 299 (1981).PubMedCrossRefGoogle Scholar
  10. 10.
    I. M. Roitt, P. N. Campbell, and D. Doniach, The nature of the thyroid auto-antibodies present in patients with Hashimoto’s thyroiditis (lymphadenoid goitre), Biochem. J. 69: 248 (1958).PubMedGoogle Scholar
  11. 11.
    L. Nye, L. C. P. DeCarvalho, and I. M. Roitt, Restrictions in the response to autologous thyroglobulin in the human, Clin. exp. Immunol. 41: 252 (1980).PubMedGoogle Scholar
  12. 12.
    H. Metzger, G. C. Sharp, and H. Edelhoch, The properties of thyroglobulin. IX. The molecular properties of iodinated thyroglobulin, Biochem. 1: 205 (1962).CrossRefGoogle Scholar
  13. 13.
    W. A. Stylos, and N. R. Rose, Splitting of human thyroglobulin. II. Enzymatic digestion, Clin. Exp. Immunol. 5: 285 (1969).PubMedGoogle Scholar
  14. 14.
    W. A. Stylos, and N. R. Rose, Splitting of human thyroglobulin. IV. The antigenicity of the pepsin derived fragments, Clin. Exp. Immunol. 27: 245 (1977).PubMedGoogle Scholar
  15. 15.
    H. Salabe, R. Dominici, G. B. Salabe, Immunological properties of Tg carbohydrates: enhancement of Tg immunoreaction by removal of sialic acid, Clin. Exp. Immunol. 25: 234 (1976).PubMedGoogle Scholar
  16. 16.
    L. A. Nilsson, N. R. Rose, and E. Witebsky, Spontaneous thyroiditis in the obese strain of chickens. VI. Thyroxine-binding antibodies, J. Immunol. 107: 997 (1971).PubMedGoogle Scholar
  17. 17.
    Y. Kondo, and Y. Kamiya, Some properties of the purified microsome-bound hog thyroid thyroglobulins: Possible intermediates in the maturation process of thyroglobulin, in: “Thyroid Research,” J. Robbins and E. L. Braverman, eds. Academic Press, New York (1975).Google Scholar
  18. 18.
    M. J. Spiro, Studies on the protein portion of thyroglobulin. Amino acid composition and terminal amino acid of several thyroglobulins, J. Biol. Chem. 245: 5820 (1970).PubMedGoogle Scholar
  19. 19.
    A. Vignal, B. M. Nataf, and M. Tubiana, Iodoamino acid composition of poorly iodinated human thyroglobulin fractionated by isopycnic centrifugation, Acta Endocrin. 87: 320 (1978).Google Scholar
  20. 20.
    T. Arima, and R. G. Spiro, Studies on the carbohydrate units of thyroglobulin. Structure of the mannose-n-acetylglucosamine unit (unit A) of the human and calf proteins, J. Biol. Chem. 247: 1836 (1972).PubMedGoogle Scholar
  21. 21.
    T. Kondo, M. Fukuda, and T. Osawa, The structure of unit B-type glycopeptides from porcine thyroglobulin, Carbohyd. Res. 58: 405 (1977).CrossRefGoogle Scholar
  22. 22.
    M. J. Spiro, and R. G. Spiro, Lipid-saccharide intermediates in thyroid glycoprotein synthesis, in: “Thyroid Research,” J. Robbins and E. L. Braverman, eds., Academic Press, New York (1975).Google Scholar
  23. 23.
    A. L. Tarentino, T. H. Plummer, and F. Maley, A 8-mannosidic linkage in the unit A oligosaccharide of bovine thyroglobulin, J. Biol. Chem. 248: 5547 (1973).PubMedGoogle Scholar
  24. 24.
    O. Tarutani, and S. Shulman, Properties of carbohydrate-stripped thyroglobulin. I. Preparation and physicochemical properties of desialized thyroglobulin, B.B.A. 229: 642 (1971).Google Scholar
  25. 25.
    O. Tarutani, and S. Shulman, Properties of carbohydrate-stripped thyroglobulin. II. Heterogeneity in sialic acid content in thyroglobulin subfractions, B.B.A. 236: 384 (1971).Google Scholar
  26. 26.
    M. Z. Atassi, Antigenic structure of myoglobin: The complete immunochemical anatomy of a protein and conclusions relating to antigenic structures of proteins, Immunochem. 12: 423 (1975).CrossRefGoogle Scholar
  27. 27.
    M. Z. Atassi, Precise determinations of the entire antigenic structure of lysozyme: molecular features of protein antigenic structures and potential of ‘surface-simulation’ synthesis - a powerful new concept for protein binding sites, Immunochem. 15: 909 (1978).CrossRefGoogle Scholar
  28. 28.
    L. Adorini, M. Harvey, and E. E. Sercarz, The fine specificity of regulatory T cells. IV. Idiotypic complementarity and antigen-bridging interactions in anti-lysozyme response, Eur. J. Immunol. 9: 906 (1979).PubMedCrossRefGoogle Scholar
  29. 29.
    L. Adorini, M. Harvey, A. Miller, and E. E. Sercarz, Fine specificity of regulatory T cells. II. Suppressor and helper T cells are induced by different regions of hen egg-white lysozyme in a genetically nonresponder mouse strain, J. Exp. Med. 150: 293 (1979).PubMedCrossRefGoogle Scholar
  30. 30.
    G. A. Hashim, and E. H. Eylar, Allergic encephalomyelitis: Isolation and characterization of encephalitogenic peptides from the basic protein of bovine spinal cord, Arch. Biochem. Biophys. 129: 645 (1969).PubMedCrossRefGoogle Scholar
  31. 31.
    C. -H. J. Chou, F. C. -H. Chou, T. J. Kowalski, R. Shapira, and R. F. Kibler, The major site of guinea pig myelin basic protein encephalitogenic in Lewis rats, J. Neurochem. 28: 115 (1977).PubMedCrossRefGoogle Scholar
  32. 32.
    J. E. Swierkosz, and R. H. Swanborg, Immunoregulation of experimental allergic encephalomyelitis: Conditions for induction of suppressor cells and analysis of mechanism, J. Immunol. 119: 1501 (1977).PubMedGoogle Scholar
  33. 33.
    A. J. Crowle, “Immunodiffusion,” Academic Press, New York (1961).Google Scholar
  34. 34.
    R. B. Goudie, J. R. Anderson, and K. G. Gray, Non-precipitating anti-thyroglobulin studied by the Ouchterlony technique, Immunol. 2: 300 (1959).Google Scholar
  35. 35.
    N. R. Rose, J. H. Kite, Jr., T. K. Doebbler and E. Witebsky, Chronic thyroiditis as an autoimmune disease, in: “Injury, Inflammation and Immunity,” L. Thomas, ed., Williams & Wilkins, Baltimore (1964).Google Scholar
  36. 36.
    J. Steensgaard, C. Jacobsen, J. Lowe, D. Hardie, N. R. Ling and R. Jefferis, The development of difference turbidimetric analysis for monoclonal antibodies to human IgG, Mol. Immunol. 17: 1315 (1980).PubMedCrossRefGoogle Scholar
  37. 37.
    Y. M. Kong, N. R. Rose, M. ElRehewy, R. Michaels, A. A. Giraldo, M. A. Accavitti and M. A. Leon, Thyroid alloantigens in autoimmunity. Trans. Proc. 12: 129 (1980).Google Scholar

Copyright information

© Plenum Press, New York 1982

Authors and Affiliations

  • N. R. Rose
    • 1
  • M. Accavitti
    • 1
  • E. F. Pydyn
    • 1
  • M. A. Leon
    • 1
  • R. K. Brown
    • 1
  1. 1.Department of Immunology and Microbiology and the Department of BiochemistryWayne State University School of MedicineDetroitUSA

Personalised recommendations