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. 1983 Jan 1;157(1):285–300. doi: 10.1084/jem.157.1.285

Identification of an idiotypic marker of a major regulatory T cell of the immune response in B10.BR mice to ferredoxin. The relationship of idiotypic regulation to conventional hapten-carrier effects

PMCID: PMC2186906  PMID: 6184440

Abstract

An anti-idiotypic antiserum was raised in rabbits to a monoclonal antibody (Fd-1) with specificity for one (the N epitope) of the two antigenic epitopes found on the ferredoxin (Fd) molecule. The anti- idiotypic antiserum (anti-Fd-1) was used to demonstrate that the Fd-1 idiotype was expressed at significant levels in most anti-Fd antisera raised in B10.BR mice. Examination of antisera raised in other mouse strains demonstrated that expression of this idiotype mapped to the IgH gene complex and was found in the antisera of all mouse strains examined with the Ig-1 allotype. When splenocytes from Fd-immune B10.Br mice were treated with anti-Fd-1 and transferred to irradiated syngeneic recipients, the adoptive secondary response was significantly higher in animals receiving treated cells as opposed to control animals, which received normal rabbit serum-treated cells. This response produced a net increase in antibody to both determinants, and the relative amount of Fd-1 idiotype was not significantly altered. Further studies with separated cell populations showed that the overall increase of anti-Fd antibody produced was attributable to the effects of the anti-idiotypic serum on a population(s) of T cells. Treatment of mice with the Fd-1 monoclonal antibody (which should react with anti- idiotypic cells) had an analogous effect to that of the anti-idiotype, in that mice so treated produced higher concentrations of anti-Fd antibodies when they were immunized and these antibodies exhibited net increases to both determinants. A model is presented to explain these results.

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Selected References

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  1. Benacerraf B. A hypothesis to relate the specificity of T lymphocytes and the activity of I region-specific Ir genes in macrophages and B lymphocytes. J Immunol. 1978 Jun;120(6):1809–1812. [PubMed] [Google Scholar]
  2. 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]
  3. Bona C. A., Heber-Katz E., Paul W. E. 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. 1981 Apr 1;153(4):951–967. doi: 10.1084/jem.153.4.951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bona C., Mongini P. K., Stein K. E., Paul W. E. Anti-immunoglobulin antibodies. I. Expression of cross-reactive idiotypes and Ir gene control of the response to IgG2a of the b allotype. J Exp Med. 1980 Jun 1;151(6):1334–1348. doi: 10.1084/jem.151.6.1334. [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. Corradin G., Chiller J. M. Lymphocyte specificity to protein antigens. II. Fine specificity of T-cell activation with cytochrome c and derived peptides as antigenic probes. J Exp Med. 1979 Feb 1;149(2):436–447. doi: 10.1084/jem.149.2.436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. GREENWOOD F. C., HUNTER W. M., GLOVER J. S. THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. Biochem J. 1963 Oct;89:114–123. doi: 10.1042/bj0890114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gleason K., Köhler H. Regulatory idiotypes. T helper cells recognize a shared VH idiotope on phosphorylcholine-specific antibodies. J Exp Med. 1982 Aug 1;156(2):539–549. doi: 10.1084/jem.156.2.539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hill S. W., Sercarz E. E. Fine specificity of the H-2 linked immune response gene for the gallinaceous lysozymes. Eur J Immunol. 1975 May;5(5):317–324. doi: 10.1002/eji.1830050506. [DOI] [PubMed] [Google Scholar]
  10. Jerne N. K. Towards a network theory of the immune system. Ann Immunol (Paris) 1974 Jan;125C(1-2):373–389. [PubMed] [Google Scholar]
  11. Ju S. T., Benacerraf B., Dorf M. E. Genetic control of a shared idiotype among antibodies directed to distinct specificities. J Exp Med. 1980 Jul 1;152(1):170–182. doi: 10.1084/jem.152.1.170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kelly B., Levy J. G., Hull D. Cellular and humoral immune responses in guinea pigs and rabbits to chemically defined synthetic peptides. Eur J Immunol. 1973 Sep;3(9):574–579. doi: 10.1002/eji.1830030910. [DOI] [PubMed] [Google Scholar]
  13. Kelly B., Levy J. G. Immunological studies on the major haptenic peptides from performic acid oxidized ferredoxin from Clostridium pasteurianum. Biochemistry. 1971 May 11;10(10):1763–1766. doi: 10.1021/bi00786a005. [DOI] [PubMed] [Google Scholar]
  14. Lamoyi E., Estess P., Capra J. D., Nisonoff A. Heterogeneity of an intrastrain cross-reactive idiotype associated with anti-p-azophenylarsonate antibodies of A/J mice. J Immunol. 1980 Jun;124(6):2834–2840. [PubMed] [Google Scholar]
  15. Liu Y. N., Bona C. A., Schulman J. L. Idiotypy of clonal responses to influenza virus hemagglutinin. J Exp Med. 1981 Nov 1;154(5):1525–1538. doi: 10.1084/jem.154.5.1525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lozner E. C., Sachs D. H., Shearer G. M. Genetic control of the immune response to staphylococcal nuclease. I. Ir-Nase: control of the antibody response to nuclease by the Ir region of the mouse H-2 complex. J Exp Med. 1974 May 1;139(5):1204–1214. doi: 10.1084/jem.139.5.1204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Okuda K., Christadoss P. R., Twining S., Atassi M. Z., David C. S. Genetic control of immune response to sperm whale myoglobin in mice. I. T lymphocyte proliferative response under H-2-linked Ir gene control. J Immunol. 1978 Sep;121(3):866–868. [PubMed] [Google Scholar]
  18. Ptak W., Zembala M., Hanczakowski-Rewicka M., Asherson G. L. Nonspecific macrophage suppressor factor: its role in the inhibition of contact sensitivity to picryl chloride by specific T suppressor factor. Eur J Immunol. 1978 Sep;8(9):645–649. doi: 10.1002/eji.1830080908. [DOI] [PubMed] [Google Scholar]
  19. Rajewsky K., Eichmann K. Antigen receptors of T helper cells. Contemp Top Immunobiol. 1977;7:69–112. doi: 10.1007/978-1-4684-3054-7_3. [DOI] [PubMed] [Google Scholar]
  20. Reth M., Imanishi-Kari T., Rajewsky K. Analysis of the repertoire of anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) antibodies in C 57 BL/6 mice by cell fusion. II. Characterization of idiotopes by monoclonal anti-idiotope antibodies. Eur J Immunol. 1979 Dec;9(12):1004–1013. doi: 10.1002/eji.1830091216. [DOI] [PubMed] [Google Scholar]
  21. Reth M., Kelsoe G., Rajewsky K. Idiotypic regulation by isologous monoclonal anti-idiotope antibodies. Nature. 1981 Mar 19;290(5803):257–259. doi: 10.1038/290257a0. [DOI] [PubMed] [Google Scholar]
  22. Rubinstein L. J., Yeh M., Bona C. A. Idiotype-anti-idiotype network. II. Activation of silent clones by treatment at birth with idiotypes is associated with the expansion of idiotype-specific helper T cells. J Exp Med. 1982 Aug 1;156(2):506–521. doi: 10.1084/jem.156.2.506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. STOLLAR D., LEVINE L., LEHRER H. I., VAN VUNAKIS H. The antigenic determinants of denatured DNA reactive with lupus erythematosus serum. Proc Natl Acad Sci U S A. 1962 May 15;48:874–880. doi: 10.1073/pnas.48.5.874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sikora L. K., Levy J. G. Genetic control of the immune response to ferredoxin: linkage and mapping of T cell proliferation and antibody production genes to the MHC of mice. J Immunol. 1980 Jun;124(6):2615–2619. [PubMed] [Google Scholar]
  25. Sikora L., Weaver M., Levy J. G. The use of unideterminant fragments of ferredoxin in the genetic mapping of determinant specificity of the immune response. Mol Immunol. 1982 May;19(5):693–703. doi: 10.1016/0161-5890(82)90371-6. [DOI] [PubMed] [Google Scholar]
  26. Weaver M. S., Sikora L., Levy J. G. The immune response to ferredoxin: characterization of a major idiotype in serum using monoclonal antibody derived by cell fusion. Mol Immunol. 1982 Jan;19(1):105–117. doi: 10.1016/0161-5890(82)90252-8. [DOI] [PubMed] [Google Scholar]
  27. 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]
  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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