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. 1983 Dec 1;158(6):1938–1947. doi: 10.1084/jem.158.6.1938

Igh variable region-restricted T cell interactions. Genetic restriction of an antigen-specific suppressor inducer factor is imparted by an I-J+ antigen-nonspecific molecule

PMCID: PMC2187167  PMID: 6196435

Abstract

Immunized Ly-1 T cells secrete an antigen-specific molecule that will induce Ly-2+ T cells to express suppressive activity. In two separate systems, factors that suppress the primary anti-sheep erythrocyte (SE) plaque-forming cell response of spleen cells in vitro (Ly-1 TsiF) or the contact sensitivity of azobenzenearsonate (ABA)-TsF1 consist of two macromolecules, one which binds antigen and is IJ-, the other which is I-J+ and does not bind antigen. Both of these chains are required for the factor's biological activity. These factors show a genetic restriction in their ability to induce suppression that is linked to the variable region of the Ig heavy chain gene complex (Igh-V). The I- J+ chain from the ABA-specific TsF1 could replace the I-J+ chain needed by the SE-specific Ly-1 TsiF for biological activity. Mixtures of ABA- binding chain with I-J+ material obtained from the SE-specific Ly-1 TsiF had no effect on the primary anti-SE response in vitro. In mixtures of SE antigen-binding chain from Ly-1 TsiF and I-J+ material from the ABA-specific TsF1, it is the I-J+ molecule that determined the factor's Igh-V restriction. Thus, the antigen-combining site of the factor determined the antigen specificity of this factor but is irrelevant to its Igh-V-linked genetic restrictions. The implications of these results for the idiotype network hypothesis are 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. 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]
  2. Cantor H., Gershon R. K. Immunological circuits: cellular composition. Fed Proc. 1979 Jun;38(7):2058–2064. [PubMed] [Google Scholar]
  3. Cunningham A. J., Szenberg A. Further improvements in the plaque technique for detecting single antibody-forming cells. Immunology. 1968 Apr;14(4):599–600. [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. Greene M. I., Bach B. A., Benacerraf B. Mechanisms of regulation of cell-mediated immunity. III. The characterization of azobenzenearsonate-specific suppressor T-cell-derived-suppressor factors. J Exp Med. 1979 May 1;149(5):1069–1083. doi: 10.1084/jem.149.5.1069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Jerne N. K. Towards a network theory of the immune system. Ann Immunol (Paris) 1974 Jan;125C(1-2):373–389. [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. 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]
  11. 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]
  12. 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]
  13. Weinberger J. Z., Benacerraf B., Dorf M. E. Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. III. Interaction of effector suppressor T cells is restricted by H-2 and Igh-V genes. J Exp Med. 1980 Jun 1;151(6):1413–1423. doi: 10.1084/jem.151.6.1413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Weinberger J. Z., Germain R. N., Benacerraf B., Dorf M. E. Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. V. Role of idiotypes in the suppressor pathway. J Exp Med. 1980 Jul 1;152(1):161–169. doi: 10.1084/jem.152.1.161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Yamauchi K., Chao N., Murphy D. B., Gershon R. K. Molecular composition of an antigen-specific, Ly-1 T suppressor inducer factor. One molecule binds antigen and is I-J-; another is I-J+, does not bind antigen, and imparts an Igh-variable region-linked restriction. J Exp Med. 1982 Mar 1;155(3):655–665. doi: 10.1084/jem.155.3.655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Yamauchi K., Murphy D., Cantor H., Gershon R. K. Analysis of antigen-specific, Ig-restricted cell-free material made by I-J+ Ly-1 cells (Ly-1 TsiF) that induces Ly-2+ cells to express suppressive activity. Eur J Immunol. 1981 Nov;11(11):905–912. doi: 10.1002/eji.1830111110. [DOI] [PubMed] [Google Scholar]

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