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. 1980 Mar 1;151(3):528–541. doi: 10.1084/jem.151.3.528

Anti-phenyltrimethylamino immunity in mice. II. L-Tyrosine-p- azophenyltrimethylammonium-induced suppressor T cells selectively inhibit the expression of B-cell clones bearing a cross-reactive idiotype

PMCID: PMC2185801  PMID: 6444660

Abstract

The anti-phenyltrimethylamino (TMA) response in A/J mice is characterized by a cross-reactive idiotype(s) (CRI) that appears linked to the Ig-Ie allotype. These findings made it attractive to look for a CRI on T cells reactive to the same TMA determinant. Thus a suppressor T-cell (Ts) assay specific for L-tyrosine-p-azophenyltrimethylammonium [tyr(TMA)] was developed. A/J mice were primed with either tyr(TMA) in complete Freund's adjuvant (CFA), L-tyrosine-azobenzenearsonate [tyr(ABA)] in CFA, or with CFA alone. 6 wk later all mice were inoculated with TMA-bovine serum albumin (BSA) in CFA, boosted with soluble TMA-BSA 3 wk later, and plaqued 7 d after the soluble boost. Priming with tyr(TMA) in CFA resulted in 66% suppression of anti-TMA plaque-forming cells (PFC) as compared with control groups primed with tyr(ABA) in CFA or CFA alone. The suppression was shown to be mediated by Ts, as only T cells but not B cells from suppressed animals transfer the suppression in adoptive cell transfer experiments into lethally irradiated recipients. The profile of the anti-TMA PFC in the suppressed and nonsuppressed animals was examined via incorporation of anti-idiotypic sera (specific for CRI-TMA) into the plaquing medium. The results of these experiments indicate that the suppression of the major CRI+-TMA PFC was virtually complete, whereas the CRI--TMA PFC are left intact. When A/J mice were primed with idiotypic antisera (anti- Id) or normal rabbit serum (NRS) rather than with the antigen on CFA alone, and the same protocol was followed thereafter, the anti-Id- inoculated mice were suppressed by 63% when compared with the NRS- primed controls. Again the suppression could be accounted for by the exclusive elimination of CRI+ anti-TMA PFC. The possibility that the antigen-induced idiotype suppression may result from idiotypic restrictions between interacting CRI+-Ts and CRT+-B cells will be discussed.

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Selected References

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

  1. Alkan S. S., Nitecki D. E., Goodman J. W. Antigen recognition and the immune response: the capacity of L-tyrosine-azobenzenearsonate to serve as a carrier for a macromolecular hapten. J Immunol. 1971 Aug;107(2):353–358. [PubMed] [Google Scholar]
  2. Baker P. J. Homeostatic control of antibody responses: a model based on the recognition of cell-associated antibody by regulatory T cells. Transplant Rev. 1975;26:3–20. doi: 10.1111/j.1600-065x.1975.tb00172.x. [DOI] [PubMed] [Google Scholar]
  3. Benjamin D. C., Teale J. M. Tolerance to azobenzenearsonate: preferential loss of the major normal cross-reactive idiotype. J Immunol. 1978 Jan;120(1):202–208. [PubMed] [Google Scholar]
  4. Binz H., Wigzell H. Shared idiotypic determinants on B and T lymphocytes reactive against the same antigenic determinants. I. Demonstration of similar or identical idiotypes on IgG molecules and T-cell receptors with specificity for the same alloantigens. J Exp Med. 1975 Jul 1;142(1):197–211. doi: 10.1084/jem.142.1.197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bona C., Paul W. E. Cellular basis of regulation of expression of idiotype. I. T-suppressor cells specific for MOPC 460 idiotype regulate the expression of cells secreting anti-TNP antibodies bearing 460 idiotype. J Exp Med. 1979 Mar 1;149(3):592–600. doi: 10.1084/jem.149.3.592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cantor H., Boyse E. Regulation of the immune response by T-cell subclasses. Contemp Top Immunobiol. 1977;7:47–67. doi: 10.1007/978-1-4684-3054-7_2. [DOI] [PubMed] [Google Scholar]
  7. Chesebro B., Metzger H. Affinity labeling of a phosphorylcholine binding mouse myeloma protein. Biochemistry. 1972 Feb 29;11(5):766–771. doi: 10.1021/bi00755a014. [DOI] [PubMed] [Google Scholar]
  8. Cosenza H., Julius M. H., Augustin A. A. Idiotypes as variable region markers: analogies between receptors on phosphorylcholine-specific T and B lymphocytes. Immunol Rev. 1977;34:3–33. doi: 10.1111/j.1600-065x.1977.tb00366.x. [DOI] [PubMed] [Google Scholar]
  9. Eichmann K., Rajewsky K. Induction of T and B cell immunity by anti-idiotypic antibody. Eur J Immunol. 1975 Oct;5(10):661–666. doi: 10.1002/eji.1830051002. [DOI] [PubMed] [Google Scholar]
  10. Golub E. S. Brain-associated theta antigen: reactivity of rabbit anti-mouse brain with mouse lymphoid cells. Cell Immunol. 1971 Aug;2(4):353–361. doi: 10.1016/0008-8749(71)90070-0. [DOI] [PubMed] [Google Scholar]
  11. Hetzelberger D., Eichmann K. Idiotype suppression. III. Induction of unresponsiveness to sensitization with anti-idiotypic antibody: identification of the cell types tolerized in high zone and in low zone, suppressor cell-mediated, idiotype suppression. Eur J Immunol. 1978 Dec;8(12):839–846. doi: 10.1002/eji.1830081204. [DOI] [PubMed] [Google Scholar]
  12. Hetzelberger D., Eichmann K. Recognition of idiotypes in lymphocyte interactions. I. Idiotypic selectivity in the cooperation between T and B lymphocytes. Eur J Immunol. 1978 Dec;8(12):846–852. doi: 10.1002/eji.1830081205. [DOI] [PubMed] [Google Scholar]
  13. Jerne N. K. Towards a network theory of the immune system. Ann Immunol (Paris) 1974 Jan;125C(1-2):373–389. [PubMed] [Google Scholar]
  14. Julius M. H., Cosenza H., Augustin A. A. Parallel expression of new idiotypes on T and B cells. Nature. 1977 Jun 2;267(5610):437–439. doi: 10.1038/267437a0. [DOI] [PubMed] [Google Scholar]
  15. Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
  16. Katz D. H., Benacerraf B. The regulatory influence of activated T cells on B cell responses to antigen. Adv Immunol. 1972;15:1–94. doi: 10.1016/s0065-2776(08)60683-5. [DOI] [PubMed] [Google Scholar]
  17. Kuettner M. G., Wang A. L., Nisonoff A. Quantitative investigations of idiotypic antibodies. VI. Idiotypic specificity as a potential genetic marker for the variable regions of mouse immunoglobulin polypeptide chains. J Exp Med. 1972 Mar 1;135(3):579–595. doi: 10.1084/jem.135.3.579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Miller J. F., Mitchell G. F. Thymus and antigen-reactive cells. Transplant Rev. 1969;1:3–42. doi: 10.1111/j.1600-065x.1969.tb00135.x. [DOI] [PubMed] [Google Scholar]
  19. Mishell R. I., Dutton R. W. Immunization of normal mouse spleen cell suspensions in vitro. Science. 1966 Aug 26;153(3739):1004–1006. doi: 10.1126/science.153.3739.1004. [DOI] [PubMed] [Google Scholar]
  20. Müller K., Gerisch G. A specific glycoprotein as the target site of adhesion blocking Fab in aggregating Dictyostelium cells. Nature. 1978 Aug 3;274(5670):445–449. doi: 10.1038/274445a0. [DOI] [PubMed] [Google Scholar]
  21. Owen F. L., Ju S. T., Nisonoff A. Binding to idiotypic determinants of large proportions of thymus-derived lymphocytes in idiotypically suppressed mice. Proc Natl Acad Sci U S A. 1977 May;74(5):2084–2088. doi: 10.1073/pnas.74.5.2084. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Owen F. L., Ju S. T., Nisonoff A. Presence on idiotype-specific suppressor T cells of receptors that interact with molecules bearing the idiotype. J Exp Med. 1977 Jun 1;145(6):1559–1566. doi: 10.1084/jem.145.6.1559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Prange C. A., Fiedler J., Nitecki D. E., Bellone C. J. Inhibition of T-antigen-binding cells by idiotypic antisera. J Exp Med. 1977 Sep 1;146(3):766–778. doi: 10.1084/jem.146.3.766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Prange C. A., Green C., Nitecki D. E., Bellone C. J. Antigen-binding lymphocytes in guinea pigs. I.B cell expansion to the monovalent antigen L-tyrosine-p-azophenyl trimethylammonium (tyr(TMA)) in the absence of antibody production. J Immunol. 1977 Apr;118(4):1311–1316. [PubMed] [Google Scholar]
  25. Taniguchi M., Hayakawa K., Tada T. Properties of antigen-specific suppressive T cell factor in the regulation of antibody response of the mouse. II. In vitro activity and evidence for the I region gene product. J Immunol. 1976 Feb;116(2):542–548. [PubMed] [Google Scholar]
  26. Tung A. S., Ju S. T., Sato S., Nisonoff A. Production of large amounts of antibodies in individual mice. J Immunol. 1976 Mar;116(3):676–681. [PubMed] [Google Scholar]
  27. Ward K., Cantor H., Nisonoff A. Analysis of the cellular basis of idiotype-specific suppression. J Immunol. 1978 Jun;120(6):2016–2019. [PubMed] [Google Scholar]
  28. Woodland R., Cantor H. Idiotype-specific T helper cells are required to induce idiotype-positive B memory cells to secrete antibody. Eur J Immunol. 1978 Aug;8(8):600–606. doi: 10.1002/eji.1830080812. [DOI] [PubMed] [Google Scholar]

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