Skip to main content

The Interleukin-2 Receptor on Normal and Malignant Lymphocytes

  • Chapter
Mechanisms of Lymphocyte Activation and Immune Regulation

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 213))

Abstract

The induction of a T-cell immune response to a foreign antigen requires the activation of T lymphocytes with receptors for the specific antigen. The human antigen-specific T-cell receptor has been shown to be a polymorphic heterodimer of α and β chains of approximately 40–50 Kd associated with three or four 20- to 28-Kd nonpolymorphic polypeptide chains identified by the T3 monoclonal antibody (1–6). T-cell activation is initiated following the interaction of antigens, mitogens, or antibodies with this complex antigen-specific T-cell receptor. First, after the interaction with antigen presented in the context of products of a major histocompatibility locus and the macrophage-derived interleukin-1, T cells express the gene encoding the lymphokine interleukin-2 (IL-2), previously termed T-cell growth factor (7,8). To exert its biological effect, IL-2 must interact with specific high-affinity membrane receptors. Resting T cells do not express IL-2 receptors, but receptors are rapidly expressed on T cells after activation with an antigen or mitogen (9–11). Thus, but after activation the genes for both proteins become expressed. A failure of the production of either the growth factor or its receptor results in failure of the T-cell immune response. Thus, both the production of IL-2 and the display of IL-2 receptors are pivotal events in the full expression of the T-cell immune response. Although the interaction of appropriately presented antigen with its specific polymorphic receptor complex confers specificity for a given immune response, the interaction of IL-2 with IL-2 receptors determines its magnitude and duration.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. J. P. Allison, B. W. Mclntyre and D. Bloch. Tumor-specific antigen of murine T lymphoma defined with monoclonal antibody. J. Immunol. 129:2293, (1982).

    Google Scholar 

  2. K. Haskins, R. Kubo, J. White, M. Pigeon, J. Kappler, and P. Marrack. The major histocompatibility complex-restricted antigen receptor on T cells. Isolation with a monoclonal antibody. J. Exp. Med. 157:1149, (1983).

    Article  Google Scholar 

  3. S. C. Meuer, K. A. Fitzgerald, R. E. Hussey, J. C. Hodgdon, S. F. Schlossman, and E. L. Reinherz. Clonotypic structures involved in antigen-specific human T cell function. J. Exp. Med. 157:705, (1985).

    Article  Google Scholar 

  4. S. M. Hedrick, D. I. Cohen, E. A. Nielsen, and M. M. Davis. Isolation of cDNA clones encoding T-cell specific membrane-associated proteins. Nature 308:149, (1984).

    Article  ADS  Google Scholar 

  5. Y. Yanagi, Y. Yoshikai, R. Leggett, S. P. Clark, I. Alexander, and T. W. Mak. A human T-cell specific cDNA clone encodes a protein having extensive homology to immunoglobulin chains. Nature 308:145, (1984).

    Article  ADS  Google Scholar 

  6. J. Borst, S. Alexander, J. Elder, and C. Terhost. The T3 complex on human T lymphocytes involves four structurally distinct glycoproteins. J. Biol. Chem. 258:5153, (1983).

    Google Scholar 

  7. D. A. Morgan, F. W. Ruscetti, and R. C. Gallo. Selective in vitro growth of T lymphocytes from normal human bone marrows. Science 193:1007, 1976.

    Article  ADS  Google Scholar 

  8. K. A. Smith. T-cell growth factor. Immuno. Rev. 51:337, (1980).

    Article  Google Scholar 

  9. R. J. Robb, A. Munck, and K. A. Smith. T-cell growth factors: quantification, specificity, and biological relevance. J. Exp. Med. 154:1455, (1981).

    Article  Google Scholar 

  10. W. C. Greene, W. J. Leonard, and J. M. Depper. Growth of human T lymphocytes: an analysis of IL-2 and the IL-2 receptor. In Progress in Hematology, Vol XIV, E. Brown (ed), Grune and Stratton, New York, (1985) p 283.

    Google Scholar 

  11. T. A. Waldmann. The structure, function, and expression of interleukin-2 receptors on normal and malignant T cells. Science, in press.

    Google Scholar 

  12. T. Uchiyama, S. Broder, and T. A. Waldmann. A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. J. Immunol. 126:1393, (1983).

    Google Scholar 

  13. W. J. Leonard, J. M. Depper, T. Uchiyama, K. A. Smith, T. A. Waldmann, and W. C. Greene. A monoclonal antibody that appears to recognize the receptor for human T cell growth factor: partial characterization of the receptor. Nature 300:267, (1982).

    Article  ADS  Google Scholar 

  14. W. J. Leonard, J. M. Depper, R. J. Robb, T. A. Waldmann, and W. C. Greene. Characterization of the human receptor for T cell growth factor. Proc. Natl. Acad. Sci. USA 80:6957. (1983).

    Article  ADS  Google Scholar 

  15. R. J. Robb, and W. C. Greene. Direct demonstration of the identity of T-cell growth factor binding protein and the Tac antigen. J. Exp. Med. 158:1332, (1983).

    Article  Google Scholar 

  16. J. M. Depper, W. J. Leonard, M. Kronke, T. A. Waldmann, and W. C. Greene. Augmentation of T-cell growth factor expression in HTLV-I-infected human leukemic T cells. J. Immunol. 133:1691, (1984).

    Google Scholar 

  17. J. M. Depper, W. J. Leonard, M. Kironke, P. Noguchi, R. Cunningham, T. A. Waldmann, and W. C. Greene. Regulation of interleukin-2 receptor expression: effects of phorbol diester, phospholipase C, and reexposure to lectin and antigen. J. Immunol. 133:3054, (1984).

    Google Scholar 

  18. R. J. Robb, W. C. Greene, and C. M. Rusk. Low and high affinity cellular receptors for interleukin 2: implications for the level of Tac antigen. J. Exp. Med. 160:1126, (1984).

    Article  Google Scholar 

  19. W. J. Leonard, J. M. Depper, T. A. Waldmann, and W. C. Greene. A monoclonal antibody to the human receptor for T cell growth factor. In Receptors and Recognition, Vol 17, M Greaves (ed), Chapman & Hall, London, (1984) p 45.

    Google Scholar 

  20. D. A. Shackelford, and I. S. Trowbridge. Induction of expression and phosphorylation of the human interleukin 2 receptor by a phorbol diester. J. Biol. Chem. 259:11706. (1984).

    Google Scholar 

  21. W. J. Leonard, J. M. Depper, G. R. Crabtree, S. Rudikoff, J. Pumphrey, R. J. Robb, M. Kronke, P. B. Svetlik, N. J. Pefffer, T. A. Waldmann, and W. C. Greene. Molecular cloning and expression of cDNAs for the human interleukin-2 receptor. Nature 311:626, (1984).

    Article  ADS  Google Scholar 

  22. W. J. Leonard, J. M. Depper, M. Kronke, N. J. Peffer, P. B. Svetlik, M. Sullivan, and W. C. Greene. Structure of the human interleukin-2 gene. Science 230:633, (1985).

    Article  ADS  Google Scholar 

  23. T. A. Waldmann, C. K. Goldman, R. J. Robb, J. M. Depper, W. J. Leonard, S. O. Sharrow, K. F. Bongiovanni, S. J. Korsmeyer, and W. C. Greene. Expression of interleukin 2 receptors on activated human B cells. J. Exp. Med. 160:1450, (1984).

    Article  Google Scholar 

  24. M. Tsudo, T. Uchiyama, and H. Uchino. Expression of Tac antigen on activated normal human B cells. J. Exp. Med. 160:612, (1984).

    Article  Google Scholar 

  25. F. Herrmann, S. A. Cannistra, H. Levine, and J. D. Griffin. Expression of interleukin 2 by gamma interferon induced human leukemic and normal leukemic and normal monocyte cells. J. Exp. Med. 162:1111, (1985).

    Article  Google Scholar 

  26. L. A. Rubin, C. C. Kurman, W. E. Biddison, N. D. Goldman, and D. L. Nelson. A monoclonal antibody 7G7/B6 binds to an epitope on the human interleukin-2 (IL-2) receptor that is distinct from that recognized by IL-2 or anti-Tac. Hvbridoma 4:91, (1985).

    Article  Google Scholar 

  27. J. M. Depper, W. J. Leonard, T. A. Waldmann, and W. C. Greene. Blockade of the interleukin-2 receptor by anti-Tac antibody: inhibition of human lymphocyte activation. J. Immunol. 131:690. (1983).

    Google Scholar 

  28. M. T. Tsudo, K. Uchiyama, Takatsuki, H. Uchino, and J. Yodoi. Modulation of Tac antigen on activated human T cells by anti-Tac monoclonal antibody. J. Immunol. 129:592, (1982).

    Google Scholar 

  29. L. M. Neckers, and J. Cossman. Transferrin receptor induction in mitogen-stimulated human T lymphocytes is required for DNA synthesis and cell division and is regulated by interleukin 2. Proc. Natl. Acad. Sci. USA 80:3494, (1983).

    Article  ADS  Google Scholar 

  30. T. Cotner, J. M. Williams, L. Christenson, H. M. Shapiro, T. B. Strom, and J. Strominger. Simultaneous flow cytometric analysis of human T cell activation antigen expression and DNA content. J. Exp. Med. 157:461, (1983).

    Article  Google Scholar 

  31. T. A. Waldmann, W. C. Greene, P. S. Sarin, C. Saxinger, W. Blayney, W. A. Blattner, C. K. Goldman, K. Bongiovanni, S. Sharrow, J. M. Depper, W. Leonard, T. Uchiyama, and R. C. Gallo. Functional and phenotypic comparison of human T cell leukemia/lymphoma virus positive adult T cell leukemia with human T cell leukemia/lymphoma virus negative Sezary leukemia. J. Clin. Invest. 73:1711, (1984).

    Article  Google Scholar 

  32. K. Takiasuki, T. Uchiyama, K. Sagawa, and J. Yodoi. Adult T cell leukemia in Japan. In topics in Hematology, S. Seno, F. Takiaku, S. Irino (eds), Excerpta Medica, Amsterdam (1977), p 73.

    Google Scholar 

  33. B. J. Poiesz, F. W. Ruscetti, A. F. Gazdar, P. A. Bunn, J. D. Minna, and R. C. Gallo. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc. Natl. Acad. Sci. USA 77:7415. (1980).

    Article  ADS  Google Scholar 

  34. Y. Wano, T. Uchiyama, K. Fukui, M. Maeda, H. Uchino, and J. Yodoi. characterization of human interleukin 2 receptor (Tac expression) in normal and leukemic T cells: coexpression of normal and aberrant receptors in HUT 102 cells. J. Immunol. 132:3005, (1984).

    Google Scholar 

  35. M. Tsudo, T. Uchiyama, H. Uchino, and J. Yodoi. Failure of regulation of Tac antigen/TCGF receptor on adult T cell leukemia cells by anti-Tac monoclonal antibody. Blood 61:1014. (1983).

    Google Scholar 

  36. T. Uchiyama, Y. Wano, M. Tsudo, H. Umadome, T. Hori, S. Tamori, J. Yodoi, M. Maeda, N. Koboyshi, and M. Hatanaka. Abnormal Expression of Interleukin-2 Receptor (Tac Antigen) in Adult T-cell Leukemia. In. Retroviruses in Human Lymphoma/Leukemia: The Fifteenth International Symposium of the Princess Takamatsu Cancer Research Fund, M. Miwa (ed), Japan Sci. Soc. Press, Tokyo, (1985) p 253.

    Google Scholar 

  37. M. Seiki, S. Hattori, Y. Hirayama, and M. Yoshida. Human adult T-cell leukemia virus: Complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA. Proc. Natl. Acad. Sci. USA 80:3618. (1983).

    Article  ADS  Google Scholar 

  38. J. G. Sodroski, C. A. Rosen, and W. A. Haseltine. Trans-acting transcriptional activation of the long terminal repeat of human T lymphotrophic viruses in infected cells. Science 225:381, (1984).

    Article  ADS  Google Scholar 

  39. T. A. Waldmann, D. L. Longo, W. J. Leonard, J. M. Depper, C. B. Thompson, M. Kronke, C. K. Goldman, S. Sharrow, K. Bongiovanni, and W. C. Greene. Interleukin-2 receptor (Tac antigen) expression in HTLV-I associated adult T-cell leukemia. Cancer Res. 45:4559. (1985).

    Google Scholar 

  40. M. Kronke, J. M. Depper, W. J. Leonard, E. S. Vitetta, T. A. Waldmann, and W. C. Greene. Anti-Tac-ricin A conjugates selectively inhibit protein synthesis in human T cell leukemia/lymphoma virus infected leukemic T cells. Blood 65:1416, (1985).

    Google Scholar 

  41. D. FitzGerald, T. A. Waldmann, M. C. Willingham, and I. Paston. Pseudomonas exotoxin-anti-Tac: cell specific immunotoxin, active against cells expressing the T-cell growth factor receptor. J. Clin. Invest. 784:966, (1984).

    Article  Google Scholar 

  42. R. W. Kozak, R. W. Atcher, O. A. Gansow, A. M. Friedman, and T. A. Waldmann. Bismuth-212 labeled anti-Tac monoclonal antibody: alpha-particle emitting radionuclides as novel modalities for radioimmunotherapy. Proc. Natl. Acad. Sci. USA 83:474, (1986).

    Article  ADS  Google Scholar 

  43. T. B. Strom, L. V. Banet, G. M. Gauiton, V. F. Kelley, A. Y. Thier, T. Diamanstein, N. L. Tilney, and R. L. Kirkman. Prolongation of cardiac allograft survival in rodent recipients treated with an anti-interleukin-2 receptor monoclonal antibody. Cancer Res. 33:561 A. (1985).

    Google Scholar 

  44. M. C. Zoumbos, P. Gascon, J. Djeu, S. R. Trost, and N. Young. Circulating activated suppressor T lymphocytes in aplastic anemia. N. Engl. J. Med. 312:257, (1985).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1987 Plenum Press, New York

About this chapter

Cite this chapter

Waldmann, T.A. (1987). The Interleukin-2 Receptor on Normal and Malignant Lymphocytes. In: Gupta, S., Paul, W.E., Fauci, A.S. (eds) Mechanisms of Lymphocyte Activation and Immune Regulation. Advances in Experimental Medicine and Biology, vol 213. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5323-2_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-5323-2_13

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-5325-6

  • Online ISBN: 978-1-4684-5323-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics