Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1982 Nov 1;156(5):1325–1334. doi: 10.1084/jem.156.5.1325

I-J-restricted interactions in the generation of azobenzenearsonate- specific suppressor T cells

PMCID: PMC2186844  PMID: 6215456

Abstract

The genetic restrictions of the activation of third-order suppressor cells (Ts3) were studied in mice, using two different types of anti- azobenzenearsonate (ABA)-immune responses, namely delayed-type hypersensitivity (DTH) and cytotoxic T lymphocyte (CTL) generation. Ts2 cells were induced in several different strains of mice by injecting monoclonal T hybridoma molecules or first-order suppressor factors (TsF1) originating in A/J (H-2a, Igh-1e) mice and then testing the TsF2 molecules derived from these Ts2 in A/J and A.By (H-2b, Igh-1e) or (A/J X A.By)F1 (H-2a/b, Igh-1e) and (C57Bl/6 X A/J)F1 (H-2b/a, Igh-1e) mice. It was shown that the activity of TsF2 was restricted to the I-J of the strain in which Ts2 was induced. By genetic analysis, restriction was shown to be due to the requirement of H-2 identity between ABA-coupled cells used for Ts3 activation and the strain of the TsF2 origin. Moreover, by using H-2-congenic ABA-coupled cells, we were also able to precisely map and demonstrate that ABA-coupled cells I-J identical to TsF2 induced in various strains were necessary for effective suppression to occur. This selective activation of Ts3 suggested the existence of I-J-related antigen presentation for suppression as the counterpart of I-A or I-A-I-E-restricted antigen presentation for positive immune responses.

Full Text

The Full Text of this article is available as a PDF (615.2 KB).

Selected References

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

  1. Bach B. A., Sherman L., Benacerraf B., Greene M. I. Mechanisms of regulation of cell-mediated immunity. II. Induction and suppression of delayed-type hypersensitivity to azobenzenearsonate-coupled syngeneic cells. J Immunol. 1978 Oct;121(4):1460–1468. [PubMed] [Google Scholar]
  2. Battisto J. R., Bloom B. R. Dual immunological unresponsiveness induced by cell membrane coupled hapten or antigen. Nature. 1966 Oct 8;212(5058):156–157. doi: 10.1038/212156a0. [DOI] [PubMed] [Google Scholar]
  3. Bromberg J. S., Benacerraf B., Greene M. I. Mechanisms of regulation of cell-mediated immunity. VII. Suppressor T cells induced by suboptimal doses of antigen plus an I-J-specific allogeneic effect. J Exp Med. 1981 Feb 1;153(2):437–449. doi: 10.1084/jem.153.2.437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bromberg J. S., Nepom J. T., Benacerraf B., Greene M. I. Hapten-coupled monoclonal anti-I-A antibodies provide a first signal for the induction of suppression. J Immunol. 1982 Feb;128(2):834–837. [PubMed] [Google Scholar]
  5. Bromberg J. S., Tominaga A., Takaoki M., Greene M. I. I-J subregion and suppressor signals. Surv Immunol Res. 1982;1(1):67–75. doi: 10.1007/BF02918242. [DOI] [PubMed] [Google Scholar]
  6. Dietz M. H., Sy M. S., Benacerraf B., Nisonoff A., Greene M. I., Germain R. N. Antigen- and receptor-driven regulatory mechanisms. VII. H-2-restricted anti-idiotypic suppressor factor from efferent suppressor T cells. J Exp Med. 1981 Feb 1;153(2):450–463. doi: 10.1084/jem.153.2.450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gershon R. K., Eardley D. D., Durum S., Green D. R., Shen F. W., Yamauchi K., Cantor H., Murphy D. B. Contrasuppression. A novel immunoregulatory activity. J Exp Med. 1981 Jun 1;153(6):1533–1546. doi: 10.1084/jem.153.6.1533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Green W. F., Colley D. G. Modulation of Schistosoma mansoni egg-induced granuloma formation: I-J restriction of T cell-mediated suppression in a chronic parasitic infection. Proc Natl Acad Sci U S A. 1981 Feb;78(2):1152–1156. doi: 10.1073/pnas.78.2.1152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Greene M. I., Ratnofsky S., Takaoki M., Sy M. S., Burakoff S., Finberg R. W. Antigen-specific suppression of cytotoxic T cell responses: an idiotype-bearing factor regulates the cytotoxic T cell response to azobenzenearsonate-coupled cells. J Immunol. 1982 Mar;128(3):1188–1191. [PubMed] [Google Scholar]
  10. Katz D. H., Benacerraf B. The function and interrelationships of T-cell receptors, Ir genes and other histocompatibility gene products. Transplant Rev. 1975;22:175–195. doi: 10.1111/j.1600-065x.1975.tb01559.x. [DOI] [PubMed] [Google Scholar]
  11. Meruelo D., Flieger N., Smith D., McDevitt H. O. In vivo or in vitro treatments with anti-I-J alloantisera abolish immunity to AKR leukemia. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2178–2182. doi: 10.1073/pnas.77.4.2178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Minami M., Honji N., Dorf M. E. Mechanism responsible for the induction of I-J restriction on TS3 suppressor cells. J Exp Med. 1982 Nov 1;156(5):1502–1515. doi: 10.1084/jem.156.5.1502. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Niederhuber J. E., Allen P. Role of I-region gene products in macrophage induction of an antibody response. II. Restriction at the level of T cell in recognition of I-J-subregion macrophage determinants. J Exp Med. 1980 May 1;151(5):1103–1113. doi: 10.1084/jem.151.5.1103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Perry L. L., Dorf M. E., Bach B. A., Benacerraf B., Greene M. I. Mechanisms of regulation of cell-mediated immunity: anti-I-A alloantisera interfere with induction and expression of T-cell-mediated immunity to cell-bound antigen in vivo. Clin Immunol Immunopathol. 1980 Mar;15(3):279–292. doi: 10.1016/0090-1229(80)90040-9. [DOI] [PubMed] [Google Scholar]
  15. Rich S. S., Rich R. R. Regulatory mechanisms in cell-mediated immune responses. III. I-region control of suppressor cell interaction with responder cells in mixed lymphocyte reactions. J Exp Med. 1976 Mar 1;143(3):672–677. doi: 10.1084/jem.143.3.672. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Rosenbaum J. T., Adelman N. E., McDevitt H. O. In vivo effects of antibodies to immune response gene products. I. Haplotype-specific suppression of humoral immune responses with a monoclonal anti-I-A. J Exp Med. 1981 Nov 1;154(5):1694–1702. doi: 10.1084/jem.154.5.1694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Sprent J., Lerner E. A., Bruce J., Symington F. W. Inhibition of T cell activation in vivo with mixtures of monoclonal antibodies specific for I-A and I-A/E molecules. J Exp Med. 1981 Jul 1;154(1):188–192. doi: 10.1084/jem.154.1.188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sunday M. E., Benacerraf B., Dorf M. E. Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. VIII. Suppressor cell pathways in cutaneous sensitivity responses. J Exp Med. 1981 Apr 1;153(4):811–822. doi: 10.1084/jem.153.4.811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Swierkosz J. E., Marrack P., Kappler J. W. Functional analysis of T cells expressing Ia antigens. I. Demonstration of helper T-cell heterogeneity. J Exp Med. 1979 Dec 1;150(6):1293–1309. doi: 10.1084/jem.150.6.1293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sy M. S., Dietz M. H., Germain R. N., Benacerraf B., Greene M. I. Antigen- and receptor-driven regulatory mechanisms. IV. Idiotype-bearing I-J+ suppressor T cell factors induce second-order suppressor T cells which express anti-idiotypic receptors. J Exp Med. 1980 May 1;151(5):1183–1195. doi: 10.1084/jem.151.5.1183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sy M. S., Miller S. D., Moorhead J. W., Claman H. N. Active suppression of 1-fluoro-2,4-dinitrobenzene-immune T cells. Requirement of an auxiliary T cell induced by antigen. J Exp Med. 1979 May 1;149(5):1197–1207. doi: 10.1084/jem.149.5.1197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sy M. S., Nisonoff A., Germain R. N., Benacerraf B., Greene M. I. Antigen- and receptor-driven regulatory mechanisms. VIII. Suppression of idiotype-negative, p-azobenzenearsonate-specific T cells results from the interaction of an anti-idiotypic second-order T suppressor cell with a cross-reactive-idiotype-positive, p-azobenzenearsonate-primed T cell target. J Exp Med. 1981 Jun 1;153(6):1415–1425. doi: 10.1084/jem.153.6.1415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tada T., Takemori T., Okumura K., Nonaka M., Tokuhisa T. Two distinct types of helper T cells involved in the secondary antibody response: independent and synergistic effects of Ia- and Ia+ helper T cells. J Exp Med. 1978 Feb 1;147(2):446–458. doi: 10.1084/jem.147.2.446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Tada T., Taniguchi M., David C. S. Properties of the antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. IV. Special subregion assignment of the gene(s) that codes for the suppressive T-cell factor in the H-2 histocompatibility complex. J Exp Med. 1976 Sep 1;144(3):713–725. doi: 10.1084/jem.144.3.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Takaoki M., Sy M. S., Whitaker B., Nepom J., Finberg R., Germain R. N., Nisonoff A., Benacerraf B., Greene M. I. Biologic activity of an idiotype-bearing suppressor T cell factor produced by a long-term T cell hybridoma. J Immunol. 1982 Jan;128(1):49–53. [PubMed] [Google Scholar]
  26. Whitaker R. B., Nepom J. T., Sy M. S., Takaoki M., Gramm C. F., Fox I., Germain R. N., Nelles M. J., Greene M. I., Benacerraf B. Suppressor factor from a T cell hybrid inhibits delayed-type hypersensitivity responses to azobenzenearsonate. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6441–6445. doi: 10.1073/pnas.78.10.6441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Yano A., Schwartz R. H., Paul W. E. Antigen presentation in the murine T-lymphocyte proliferative response. I. Requirement for genetic identity at the major histocompatibility complex. J Exp Med. 1977 Sep 1;146(3):828–843. doi: 10.1084/jem.146.3.828. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES