Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1983 Dec 1;158(6):1962–1978. doi: 10.1084/jem.158.6.1962

Antigen-specific suppressor T cell interactions. II. Characterization of two different types of suppressor T cell factors specific for L- glutamic acid50-L-tyrosine50 (GT) and L-glutamic acid60-L-alanine30-L- tyrosine10 (GAT)

PMCID: PMC2187171  PMID: 6606014

Abstract

We have previously reported that two types of suppressor T cell factors (TsF) specific for L-glutamic acid50-L-tyrosine50 (GT) or L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) can be distinguished based upon differences in their ability to suppress responses by allogeneic mice. Injection of GAT or GT induces a suppressor T cell subset that produces an antigen-binding, I-J+, genetically unrestricted, specific suppressor factor (TsF1). Injection of this factor plus small amounts of antigen induces a second-order suppressor T cell that produces an antigen- binding, I-J+, genetically restricted, specific suppressor factor (TsF2). In this report, we demonstrate that these two factors are also biochemically distinct. Monoclonal TsF1 molecules are composed of a single polypeptide chain that bears both the antigen-binding site and I- J determinant, whereas TsF2 molecules are composed of two disulfide- linked polypeptide chains, one of which is antigen-binding and I-J-, and the other, nonantigen-binding, I-J+. The antigen-binding chain must be added at culture initiation to achieve suppression, but the I-J+ chain can be added as late as day 3 with complete suppression observed. However, isolated chains from TsF2-producing hybridomas derived from three different haplotypes were unable to suppress immune responses when chains from heterologous TsF2 were mixed. Indirect evidence is presented that suggests that this restriction is because the chains fail to interact rather than the inability of the target cells to recognize both chains.

Full Text

The Full Text of this article is available as a PDF (1.2 MB).

Selected References

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

  1. Araneo B. A., Kapp J. A. Genetic analysis of immune suppression. I. Gene complementation is required for suppression of antigen-specific proliferative responses by T-cell derived factors. Immunogenetics. 1981;14(3-4):221–230. doi: 10.1007/BF00342191. [DOI] [PubMed] [Google Scholar]
  2. Araneo B. A., Kapp J. A. Immunosuppressive factor(s) from lymphoid cells of nonresponder mice primed with L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT). V. Inhibition of T cell proliferative responses. J Immunol. 1980 Jul;125(1):118–123. [PubMed] [Google Scholar]
  3. Bach B. A., Greene M. I., Benacerraf B., Nisonoff A. Mechanisms of regulation of cell-mediated immunity. IV. Azobenzenearsonate-specific suppressor factor(s) bear cross-reactive idiotypic determinants the expression of which is linked to the heavy-chain allotype linkage group of genes. J Exp Med. 1979 May 1;149(5):1084–1098. doi: 10.1084/jem.149.5.1084. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Debré P., Kapp J. A., Dorf M. E., Benacerraf B. Genetic control of specific immune suppression. II. H-2-linked dominant genetic control of immune suppression by the random copolymer L-glutamic acid50-L-tyrosine50 (GT). J Exp Med. 1975 Dec 1;142(6):1447–1454. doi: 10.1084/jem.142.6.1447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Germain R. N., Ju S. T., Kipps T. J., Benacerraf B., Dorf M. E. Shared idiotypic determinants on antibodies and T-cell-derived suppressor factor specific for the random terpolymer L-glutamic acid60-L-alanine30-L-tyrosine10. J Exp Med. 1979 Mar 1;149(3):613–622. doi: 10.1084/jem.149.3.613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Germain R. N., Theze J., Waltenbaugh C., Dorf M. E., Benacerraf B. Antigen-specific T cell-mediated suppression. II. In vitro induction by I-J-coded L-glutamic acid50-L-tyrosine50 (GT)-specific T cell suppressor factor (GT-T8F) of suppressor T cells (T82) bearing distinct I-J determinants. J Immunol. 1978 Aug;121(2):602–607. [PubMed] [Google Scholar]
  8. Germain R. N., Thèze J., Kapp J. A., Benacerraf B. Antigen-specific T-cell-mediated suppression. I. Induction of L-glutamic acid60-L-alanine30-L-tyrosine10 specific suppressor T cells in vitro requires both antigen-specific T-cell-suppressor factor and antigen. J Exp Med. 1978 Jan 1;147(1):123–136. doi: 10.1084/jem.147.1.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Herzenberg L. A., Okumura K., Cantor H., Sato V. L., Shen F. W., Boyse E. A., Herzenberg L. A. T-cell regulation of antibody responses: demonstration of allotype-specific helper T cells and their specific removal by suppressor T cells. J Exp Med. 1976 Aug 1;144(2):330–344. doi: 10.1084/jem.144.2.330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hirashima M., Yodoi J., Ishizaka K. Regulatory role of IgE-binding factors from rat T lymphocytes. III. IgE-specific suppressive factor with IgE-binding activity. J Immunol. 1980 Oct;125(4):1442–1448. [PubMed] [Google Scholar]
  11. Ju S. T., Pierres M., Germain R. N., Benacerraf B., Dorf M. E. Idiotypic analysis of anti-GAT antibodies. VI. Identification and strain distribution of the GA-1 idiotype. J Immunol. 1979 Dec;123(6):2505–2510. [PubMed] [Google Scholar]
  12. Kapp J. A., Araneo B. A. Antigen-specific suppressor T cell interactions. I. Induction of an MHC-restricted suppressor factor specific for L-glutamic acid50-L-tyrosine50. J Immunol. 1982 Jun;128(6):2447–2452. [PubMed] [Google Scholar]
  13. Kapp J. A., Araneo B. A., Clevinger B. L. Suppression of antibody and T cell proliferative responses to L-glutamic acid60-L-alanine30-L-tyrosine10 by a specific monoclonal T cell factor. J Exp Med. 1980 Jul 1;152(1):235–240. doi: 10.1084/jem.152.1.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kapp J. A. Immunosuppressive factors from lymphoid cells of nonresponder mice primed with L-glutamic acid60-L-alanine30-L-tyrosine10. IV. Lack of strain restrictions among allogeneic, nonresponder donors and recipients. J Exp Med. 1978 Apr 1;147(4):997–1006. doi: 10.1084/jem.147.4.997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kapp J. A., Pierce C. W., Benacerraf B. Genetic control of immune responses in vitro. I. Development of primary and secondary plaque-forming cell responses to the random terpolymer 1-glutamic acid 60-1-alanine30-1-tyrosine10 (GAT) by mouse spleen cells in vitro. J Exp Med. 1973 Nov 1;138(5):1107–1120. doi: 10.1084/jem.138.5.1107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kapp J. A., Pierce C. W., De la Croix F., Benacerraf B. Immunosuppressive factor(s) extracted from lymphoid cells of nonresponder mice primed with L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT). J Immunol. 1976 Feb;116(2):305–309. [PubMed] [Google Scholar]
  17. Kapp J. A., Pierce C. W., Schlossman S., Benacerraf B. Genetic control of immune responses in vitro. V. Stimulation of suppressor T cells in nonresponder mice by the terpolymer L-glutamic acid 60-L-alanine 30-L-tyrosine 10 (GAT). J Exp Med. 1974 Sep 1;140(3):648–659. doi: 10.1084/jem.140.3.648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kontiainen S., Feldmann M. Suppressor-cell induction in vitro. IV. Target of antigen-specific suppressor factor and its genetic relationships. J Exp Med. 1978 Jan 1;147(1):110–122. doi: 10.1084/jem.147.1.110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kontiainen S., Simpson E., Bohrer E., Beverley P. C., Herzenberg L. A., Fitzpatrick W. C., Vogt P., Torano A., McKenzie I. F., Feldmann M. T-cell lines producing antigen-specific suppressor factor. Nature. 1978 Aug 3;274(5670):477–480. doi: 10.1038/274477a0. [DOI] [PubMed] [Google Scholar]
  20. Krupen K., Araneo B. A., Brink L., Kapp J. A., Stein S., Wieder K. J., Webb D. R. Purification and characterization of a monoclonal T-cell suppressor factor specific for poly(LGlu60LAla30LTyr10). Proc Natl Acad Sci U S A. 1982 Feb;79(4):1254–1258. doi: 10.1073/pnas.79.4.1254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lando Z., Dori Y., Teitelbaum D., Arnon R. Lack of H-2 restriction of suppressor factor specific to myelin basic encephalitogen. J Neurol Sci. 1982 Jan;53(1):113–123. doi: 10.1016/0022-510x(82)90085-5. [DOI] [PubMed] [Google Scholar]
  22. Lei H. Y., Ju S. T., Dorf M. E., Waltenbaugh C. Regulation of immune responses by I-J gene products. III. GT-specific suppressor factor is composed of separate I-J and idiotype-bearing chains. J Immunol. 1983 Mar;130(3):1274–1279. [PubMed] [Google Scholar]
  23. OLINS D. E., EDELMAN G. M. RECONSTITUTION OF 7S MOLECULES FROM L AND H POLYPEPTIDE CHAINS OF ANTIBODIES AND GAMMA-GLOBULINS. J Exp Med. 1964 May 1;119:789–815. doi: 10.1084/jem.119.5.789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Okuda K., Minami M., Furusawa M., Dorf M. E. Analysis of T cell hybridomas. II. Comparisons among three distinct types of monoclonal suppressor factors. J Exp Med. 1981 Dec 1;154(6):1838–1851. doi: 10.1084/jem.154.6.1838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Okuda K., Minami M., Sherr D. H., Dorf M. E. Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. XI. Pseudogenetic restrictions of hybridoma suppressor factors. J Exp Med. 1981 Aug 1;154(2):468–479. doi: 10.1084/jem.154.2.468. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pierres M., Ju S. T., Waltenbaugh C., Dorf M. E., Benacerraf B., Germain R. N. Fine specificity of antibodies to poly(Glu60Ala30Tyr10) produced by hybrid cell lines. Proc Natl Acad Sci U S A. 1979 May;76(5):2425–2429. doi: 10.1073/pnas.76.5.2425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sorensen C. M., Pierce C. W. Antigen-specific suppression in genetic responder mice to L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT). Characterization of conventional and hybridoma-derived factors produced by suppressor T cells from mice injected as neonates with syngeneic GAT macrophages. J Exp Med. 1982 Dec 1;156(6):1691–1710. doi: 10.1084/jem.156.6.1691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Suemura M., Shiho O., Deguchi H., Yamamura Y., Böttcher I., Kishimoto T. Characterization and isolation of IgE class-specific suppressor factor (IgE-TsF) I. The presence of the binding site(s) for IgE and of the H-2 gene products in IgE-TsF. J Immunol. 1981 Aug;127(2):465–471. [PubMed] [Google Scholar]
  29. Tada T., Okumura K. The role of antigen-specific T cell factors in the immune response. Adv Immunol. 1979;28:1–87. doi: 10.1016/s0065-2776(08)60799-3. [DOI] [PubMed] [Google Scholar]
  30. Taniguchi M., Saito T., Takei I., Tokuhisa T. Presence of interchain disulfide bonds between two gene products that compose the secreted form of an antigen-specific suppressor factor. J Exp Med. 1981 Jun 1;153(6):1672–1677. doi: 10.1084/jem.153.6.1672. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Taniguchi M., Takei I., Tada T. Functional and molecular organisation of an antigen-specific suppressor factor from a T-cell hybridoma. Nature. 1980 Jan 10;283(5743):227–228. doi: 10.1038/283227a0. [DOI] [PubMed] [Google Scholar]
  32. Theze J., Kapp J. A., Benacerraf B. Immunosuppressive factor(s) extracted from lymphoid cells of nonresponder mice primed with L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) III. Immunochemical properties of the GAT-specific suppressive factor. J Exp Med. 1977 Apr 1;145(4):839–856. doi: 10.1084/jem.145.4.839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Thèze J., Waltenbaugh C., Germain R. N., Benacerraf B. Immunosuppressive factor(s) specific for L-glutamic acid50-L-tyosine50. IV. In vitro activity and immunochemical properties. Eur J Immunol. 1977 Oct;7(10):705–710. doi: 10.1002/eji.1830071011. [DOI] [PubMed] [Google Scholar]
  34. Waltenbaugh C., Debré P., Thèze J., Benacerraf B. Immunosuppressive factor(s) specific for L-glutamic acid50-L-tyrosine50 (GT). I. Production, characterization, and lack of H-2 restriction for activity in recipient strain. J Immunol. 1977 Jun;118(6):2073–2077. [PubMed] [Google Scholar]
  35. Waltenbaugh C. Regulation of immune responses by I-J gene products. I. Production and characterization of anti-I-J monoclonal antibodies. J Exp Med. 1981 Nov 1;154(5):1570–1583. doi: 10.1084/jem.154.5.1570. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES