Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1996 Jul 9;93(14):7207–7212. doi: 10.1073/pnas.93.14.7207

Cellular mechanisms for the formation of a soluble form derivative of T-cell receptor alpha chain by suppressor T cells.

Y Ishii 1, T Nakano 1, K Ishizaka 1
PMCID: PMC38961  PMID: 8692970

Abstract

Upon stimulation with anti-CD3, suppressor T-cell (Ts) hybridomas and homologous transfectants of T-cell receptor a (TCRalpha) cDNA in the T-cell hybridoma formed a 55-kDa TCRalpha chain derivative that bound both the monoclonal anti-TCRalpha chain and polyclonal antibodies against glycosylation inhibiting factor (GIF). The peptide is a subunit of antigen-specific suppressor T-cell factor (TsF), and is considered to be a posttranslationally-formed conjugate of TCRalpha chain with GIF peptide. The TCRalpha derivative is synthesized by the transfectant after stimulation with anti-CD3, and not derived from TCR present on the cell surface. Stimulation of the stable homologous transfectants with anti-CD3 induced translocation of the 13-kDa GIF peptide into endoplasmic reticulum (ER). When a helper Ts hybridoma or a stable transfectant of the same TCRalpha cDNA in a helper cell-derived TCRalpha- clone was stimulated with anti-CD3, translocation of GIF peptide was not detected, and these cells failed to secrete a TCRalpha derivative. However, further transfection of a chimeric cDNA encoding a procalcitonin-GIF fusion protein into the helper cell-derived stable transfectant of TCRalpha cDNA resulted in translocation of the GIF protein and formation of bioactive 55-kDa GIF. The results indicated that translocation of GIF peptide through ER is unique for Ts cells, and that this process is essential for the formation/secretion of the soluble form derivative of TCRalpha chain by T cells.

Full text

PDF
7207

Images in this article

Selected References

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

  1. Akasaki M., Jardieu P., Ishizaka K. Immunosuppressive effects of glycosylation inhibiting factor on the IgE and IgG antibody response. J Immunol. 1986 May 1;136(9):3172–3179. [PubMed] [Google Scholar]
  2. Becker M. L., Near R., Mudgett-Hunter M., Margolies M. N., Kubo R. T., Kaye J., Hedrick S. M. Expression of a hybrid immunoglobulin-T cell receptor protein in transgenic mice. Cell. 1989 Sep 8;58(5):911–921. doi: 10.1016/0092-8674(89)90943-4. [DOI] [PubMed] [Google Scholar]
  3. Bissonnette R., Zheng H. G., Kubo R. T., Singh B., Green D. R. A T helper cell hybridoma produces an antigen-specific regulatory activity. Relationship to the T cell receptor by serology and antigenic fine specificity. J Immunol. 1991 May 1;146(9):2898–2907. [PubMed] [Google Scholar]
  4. Bonifacino J. S., Cosson P., Klausner R. D. Colocalized transmembrane determinants for ER degradation and subunit assembly explain the intracellular fate of TCR chains. Cell. 1990 Nov 2;63(3):503–513. doi: 10.1016/0092-8674(90)90447-m. [DOI] [PubMed] [Google Scholar]
  5. Collins M., Kuchroo V. K., Whitters M. J., O'Hara R. M., Jr, Kelleher K., Kubo R. T., Dorf M. E. Expression of functional alpha beta T cell receptor gene rearrangements in suppressor T cell hybridomas correlates with antigen binding, but not with suppressor cell function. J Immunol. 1990 Nov 1;145(9):2809–2819. [PubMed] [Google Scholar]
  6. Dorf M. E., Benacerraf B. Suppressor cells and immunoregulation. Annu Rev Immunol. 1984;2:127–157. doi: 10.1146/annurev.iy.02.040184.001015. [DOI] [PubMed] [Google Scholar]
  7. Fairchild R. L., Kubo R. T., Moorhead J. W. DNP-specific/class I MHC-restricted suppressor molecules bear determinants of the T cell receptor alpha- and beta-chains. The V beta 8+ chain dictates restriction to either K or D. J Immunol. 1990 Oct 1;145(7):2001–2009. [PubMed] [Google Scholar]
  8. Glaichenhaus N., Davis C., Bornschlegel K., Allison J. P., Shastri N. A novel strategy for the generation of T cell lines lacking expression of endogenous alpha- and/or beta-chain T cell receptor genes. J Immunol. 1991 Apr 1;146(7):2095–2101. [PubMed] [Google Scholar]
  9. Ishii Y., Nakano T., Ishizaka K. Biochemical characterization of antigen-specific glycosylation-inhibiting factor from antigen-specific suppressor T cells. II. The 55-kDa glycosylation-inhibiting factor peptide is a derivative of TCR alpha-chain and a subunit of antigen-specific glycosylation-inhibiting factor. J Immunol. 1996 Mar 1;156(5):1735–1742. [PubMed] [Google Scholar]
  10. Iwata M., Ishizaka K. Construction of antigen-specific suppressor T cell hybridomas from spleen cells of mice primed for the persistent IgE antibody formation. J Immunol. 1988 Nov 15;141(10):3270–3277. [PubMed] [Google Scholar]
  11. Iwata M., Katamura K., Kubo R. T., Grey H. M., Ishizaka K. Relationship between T cell receptors and antigen-binding factors. II. Common antigenic determinants and epitope recognition shared by T cell receptors and antigen-binding factors. J Immunol. 1989 Dec 15;143(12):3917–3924. [PubMed] [Google Scholar]
  12. Iwata M., Katamura K., Mori A., Yamagushi K., Grey H., Ishizaka K. Association of glycosylation-inhibiting factor with plasma membranes of T suppressor cell hybridomas. J Immunol. 1990 Dec 1;145(11):3578–3588. [PubMed] [Google Scholar]
  13. Janknecht R., de Martynoff G., Lou J., Hipskind R. A., Nordheim A., Stunnenberg H. G. Rapid and efficient purification of native histidine-tagged protein expressed by recombinant vaccinia virus. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):8972–8976. doi: 10.1073/pnas.88.20.8972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jardieu P., Akasaki M., Ishizaka K. Carrier-specific suppression of antibody responses by antigen-specific glycosylation-inhibiting factors. J Immunol. 1987 Mar 1;138(5):1494–1501. [PubMed] [Google Scholar]
  15. Klausner R. D., Lippincott-Schwartz J., Bonifacino J. S. The T cell antigen receptor: insights into organelle biology. Annu Rev Cell Biol. 1990;6:403–431. doi: 10.1146/annurev.cb.06.110190.002155. [DOI] [PubMed] [Google Scholar]
  16. Kubo R. T., Born W., Kappler J. W., Marrack P., Pigeon M. Characterization of a monoclonal antibody which detects all murine alpha beta T cell receptors. J Immunol. 1989 Apr 15;142(8):2736–2742. [PubMed] [Google Scholar]
  17. Kuchroo V. K., Byrne M. C., Atsumi Y., Greenfield E., Connolly J. B., Whitters M. J., O'Hara R. M., Jr, Collins M., Dorf M. E. T-cell receptor alpha chain plays a critical role in antigen-specific suppressor cell function. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8700–8704. doi: 10.1073/pnas.88.19.8700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kuchroo V. K., Byrne M. C., Greenfield E., Whitters M. J., Nalefsky E. A., Rao A., Collins M., Dorf M. E. Transfection of TCR alpha-chains into suppressor and T helper cell hybridomas. Production of suppressor factors with predicted antigen specificity. J Immunol. 1995 May 15;154(10):5030–5038. [PubMed] [Google Scholar]
  19. Kuchroo V. K., Steele J. K., O'Hara R. M., Jr, Jayaraman S., Selvaraj P., Greenfield E., Kubo R. T., Dorf M. E. Relationships between antigen-specific helper and inducer suppressor T cell hybridomas. J Immunol. 1990 Jul 15;145(2):438–448. [PubMed] [Google Scholar]
  20. Leo O., Foo M., Sachs D. H., Samelson L. E., Bluestone J. A. Identification of a monoclonal antibody specific for a murine T3 polypeptide. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1374–1378. doi: 10.1073/pnas.84.5.1374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Liu Y. C., Nakano T., Elly C., Ishizaka K. Requirement of posttranslational modifications for the generation of biologic activity of glycosylation-inhibiting factor. Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11227–11231. doi: 10.1073/pnas.91.23.11227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mikayama T., Nakano T., Gomi H., Nakagawa Y., Liu Y. C., Sato M., Iwamatsu A., Ishii Y., Weiser W. Y., Ishizaka K. Molecular cloning and functional expression of a cDNA encoding glycosylation-inhibiting factor. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10056–10060. doi: 10.1073/pnas.90.21.10056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mori A., Thomas P., Tagaya Y., Iijima H., Grey H., Ishizaka K. Epitope specificity of bee venom phospholipase A2-specific suppressor T cells which produce antigen-binding glycosylation inhibiting factor. Int Immunol. 1993 Aug;5(8):833–842. doi: 10.1093/intimm/5.8.833. [DOI] [PubMed] [Google Scholar]
  24. Nakano T., Ishii Y., Ishizaka K. Biochemical characterization of antigen-specific glycosylation-inhibiting factor from antigen-specific suppressor T cells. I. Identification of a 55-kilodalton glycosylation-inhibiting factor peptide with TCR alpha-chain determinant. J Immunol. 1996 Mar 1;156(5):1728–1734. [PubMed] [Google Scholar]
  25. Nakano T., Liu Y. C., Mikayama T., Watarai H., Taniguchi M., Ishizaka K. Association of the "major histocompatibility complex subregion" I-J determinant with bioactive glycosylation-inhibiting factor. Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9196–9200. doi: 10.1073/pnas.92.20.9196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Shimonkevitz R., Kappler J., Marrack P., Grey H. Antigen recognition by H-2-restricted T cells. I. Cell-free antigen processing. J Exp Med. 1983 Aug 1;158(2):303–316. doi: 10.1084/jem.158.2.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Shin J., Lee S., Strominger J. L. Translocation of TCR alpha chains into the lumen of the endoplasmic reticulum and their degradation. Science. 1993 Mar 26;259(5103):1901–1904. doi: 10.1126/science.8456316. [DOI] [PubMed] [Google Scholar]
  28. Steele J. K., Kuchroo V. K., Kawasaki H., Jayaraman S., Iwata M., Ishizaka K., Dorf M. E. A monoclonal antibody raised to lipomodulin recognizes T suppressor factors in two independent hapten-specific suppressor networks. J Immunol. 1989 Apr 1;142(7):2213–2220. [PubMed] [Google Scholar]
  29. Takata M., Maiti P. K., Kubo R. T., Chen Y. H., Holford-Strevens V., Rector E. S., Sehon A. H. Cloned suppressor T cells derived from mice tolerized with conjugates of antigen and monomethoxypolyethylene glycol. Relationship between monoclonal T suppressor factor and the T cell receptor. J Immunol. 1990 Nov 1;145(9):2846–2853. [PubMed] [Google Scholar]
  30. Webb D. R., Kapp J. A., Pierce C. W. The biochemistry of antigen-specific T-cell factors. Annu Rev Immunol. 1983;1:423–438. doi: 10.1146/annurev.iy.01.040183.002231. [DOI] [PubMed] [Google Scholar]
  31. Zheng H., Sahai B. M., Kilgannon P., Fotedar A., Green D. R. Specific inhibition of cell-surface T-cell receptor expression by antisense oligodeoxynucleotides and its effect on the production of an antigen-specific regulatory T-cell factor. Proc Natl Acad Sci U S A. 1989 May;86(10):3758–3762. doi: 10.1073/pnas.86.10.3758. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES