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. 1986 Oct 1;164(4):1060–1074. doi: 10.1084/jem.164.4.1060

Binding and internalization of interleukin 1 by T cells. Direct evidence for high- and low-affinity classes of interleukin 1 receptor

PMCID: PMC2188417  PMID: 2944981

Abstract

In this report we describe, on the basis of direct IL-1 binding assays and IL-1 internalization studies, the existence of two classes of IL-1- R on a variety of T cell types. Cells of the EL4-6.1 thymoma express large numbers (approximately 20,000 per cell) of IL-1-R that have a Kd of approximately 300 pM for IL-1. Even though these receptors make up 98-99% of the total IL-1-R per cell, they appear to be nonfunctional, based on their inability to endocytose IL-1. A minor class of IL-1-R (200-400/cell) has an approximately 100-fold higher affinity for IL-1 (Kd, approximately 5 pM) and can rapidly internalize the ligand upon binding. All of the biological activity of IL-1 can be shown to occur via binding to high-affinity IL-1-R since the IL-1 concentration giving half-maximum biological activity in EL4-6.1 cells corresponds precisely to the Kd of this class of receptor. Other cell types, including normal T cells, also express both high- and low-affinity IL-1-R, but the absolute number of receptors per cell is considerably less.

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Selected References

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  1. Carpentier J. L., Gorden P., Amherdt M., Van Obberghen E., Kahn C. R., Orci L. 125I-insulin binding to cultured human lymphocytes. Initial localization and fate of hormone determined by quantitative electron microscopic autoradiography. J Clin Invest. 1978 Apr;61(4):1057–1070. doi: 10.1172/JCI109005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cerottini J. C., Engers H. D., Macdonald H. R., Brunner T. Generation of cytotoxic T lymphocytes in vitro. I. Response of normal and immune mouse spleen cells in mixed leukocyte cultures. J Exp Med. 1974 Sep 1;140(3):703–717. doi: 10.1084/jem.140.3.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Conlon P. J. A rapid biologic assay for the detection of interleukin 1. J Immunol. 1983 Sep;131(3):1280–1282. [PubMed] [Google Scholar]
  4. Corin R. E., Donner D. B. Insulin receptors convert to a higher affinity state subsequent to hormone binding. A two-state model for the insulin receptor. J Biol Chem. 1982 Jan 10;257(1):104–110. [PubMed] [Google Scholar]
  5. Culvenor J. G., Harris A. W., Mandel T. E., Whitelaw A., Ferber E. Alkaline phosphatase in hematopoietic tumor cell lines of the mouse: high activity in cells of the B lymphoid lineage. J Immunol. 1981 May;126(5):1974–1977. [PubMed] [Google Scholar]
  6. Dower S. K., Call S. M., Gillis S., Urdal D. L. Similarity between the interleukin 1 receptors on a murine T-lymphoma cell line and on a murine fibroblast cell line. Proc Natl Acad Sci U S A. 1986 Feb;83(4):1060–1064. doi: 10.1073/pnas.83.4.1060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dower S. K., Kronheim S. R., March C. J., Conlon P. J., Hopp T. P., Gillis S., Urdal D. L. Detection and characterization of high affinity plasma membrane receptors for human interleukin 1. J Exp Med. 1985 Aug 1;162(2):501–515. doi: 10.1084/jem.162.2.501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Durum S. K., Schmidt J. A., Oppenheim J. J. Interleukin 1: an immunological perspective. Annu Rev Immunol. 1985;3:263–287. doi: 10.1146/annurev.iy.03.040185.001403. [DOI] [PubMed] [Google Scholar]
  9. Erard F., Nabholz M., Dupuy-D'Angeac A., MacDonald H. R. Differential requirements for the induction of interleukin 2 responsiveness in L3T4+ and Lyt-2+ T cell subsets. J Exp Med. 1985 Nov 1;162(5):1738–1743. doi: 10.1084/jem.162.5.1738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Farrar J. J., Mizel S. B., Fuller-Farrar J., Farrar W. L., Hilfiker M. L. Macrophage-independent activation of helper T cells. I. Production of Interleukin 2. J Immunol. 1980 Aug;125(2):793–798. [PubMed] [Google Scholar]
  11. Fujii M., Sugamura K., Sano K., Nakai M., Sugita K., Hinuma Y. High-affinity receptor-mediated internalization and degradation of interleukin 2 in human T cells. J Exp Med. 1986 Mar 1;163(3):550–562. doi: 10.1084/jem.163.3.550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gillis S., Ferm M. M., Ou W., Smith K. A. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed] [Google Scholar]
  13. Gillis S., Mizel S. B. T-Cell lymphoma model for the analysis of interleukin 1-mediated T-cell activation. Proc Natl Acad Sci U S A. 1981 Feb;78(2):1133–1137. doi: 10.1073/pnas.78.2.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Goldstein J. L., Anderson R. G., Brown M. S. Coated pits, coated vesicles, and receptor-mediated endocytosis. Nature. 1979 Jun 21;279(5715):679–685. doi: 10.1038/279679a0. [DOI] [PubMed] [Google Scholar]
  15. Gorden P., Carpentier J. L., Cohen S., Orci L. Epidermal growth factor: morphological demonstration of binding, internalization, and lysosomal association in human fibroblasts. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5025–5029. doi: 10.1073/pnas.75.10.5025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. HUNTER W. M., GREENWOOD F. C. Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature. 1962 May 5;194:495–496. doi: 10.1038/194495a0. [DOI] [PubMed] [Google Scholar]
  17. Habu S., Okumura K. Cell surface antigen marking the stages of murine T cell ontogeny and its functional subsets. Immunol Rev. 1984 Dec;82:117–139. doi: 10.1111/j.1600-065x.1984.tb01120.x. [DOI] [PubMed] [Google Scholar]
  18. Hyman R., Stallings V. Complementation patterns of Thy-1 variants and evidence that antigen loss variants "pre-exist" in the parental population. J Natl Cancer Inst. 1974 Feb;52(2):429–436. doi: 10.1093/jnci/52.2.429. [DOI] [PubMed] [Google Scholar]
  19. Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
  20. Kasahara T., Mukaida N., Hatake K., Motoyoshi K., Kawai T., Shiori-Nakano K. Interleukin 1 (IL 1)-dependent lymphokine production by human leukemic T cell line HSB.2 subclones. J Immunol. 1985 Mar;134(3):1682–1689. [PubMed] [Google Scholar]
  21. Kaye J., Gillis S., Mizel S. B., Shevach E. M., Malek T. R., Dinarello C. A., Lachman L. B., Janeway C. A., Jr Growth of a cloned helper T cell line induced by a monoclonal antibody specific for the antigen receptor: interleukin 1 is required for the expression of receptors for interleukin 2. J Immunol. 1984 Sep;133(3):1339–1345. [PubMed] [Google Scholar]
  22. Larsson E. L., Iscove N. N., Coutinho A. Two distinct factors are required for induction of T-cell growth. Nature. 1980 Feb 14;283(5748):664–666. doi: 10.1038/283664a0. [DOI] [PubMed] [Google Scholar]
  23. Lowenthal J. W., Zubler R. H., Nabholz M., MacDonald H. R. Similarities between interleukin-2 receptor number and affinity on activated B and T lymphocytes. Nature. 1985 Jun 20;315(6021):669–672. doi: 10.1038/315669a0. [DOI] [PubMed] [Google Scholar]
  24. Maizel A. L., Mehta S. R., Ford R. J., Lachman L. B. Effect of interleukin 1 on human thymocytes and purified human T cells. J Exp Med. 1981 Feb 1;153(2):470–475. doi: 10.1084/jem.153.2.470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. March C. J., Mosley B., Larsen A., Cerretti D. P., Braedt G., Price V., Gillis S., Henney C. S., Kronheim S. R., Grabstein K. Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature. 1985 Jun 20;315(6021):641–647. doi: 10.1038/315641a0. [DOI] [PubMed] [Google Scholar]
  26. Mizel S. B. Interleukin 1 and T cell activation. Immunol Rev. 1982;63:51–72. doi: 10.1111/j.1600-065x.1982.tb00411.x. [DOI] [PubMed] [Google Scholar]
  27. Nicola N. A., Metcalf D. Binding of the differentiation-inducer, granulocyte-colony-stimulating factor, to responsive but not unresponsive leukemic cell lines. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3765–3769. doi: 10.1073/pnas.81.12.3765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Robb R. J., Greene W. C., Rusk C. M. Low and high affinity cellular receptors for interleukin 2. Implications for the level of Tac antigen. J Exp Med. 1984 Oct 1;160(4):1126–1146. doi: 10.1084/jem.160.4.1126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Robb R. J., Mayer P. C., Garlick R. Retention of biological activity following radioiodination of human interleukin 2: comparison with biosynthetically labeled growth factor in receptor binding assays. J Immunol Methods. 1985 Jul 16;81(1):15–30. doi: 10.1016/0022-1759(85)90118-8. [DOI] [PubMed] [Google Scholar]
  30. Robb R. J., Munck A., Smith K. A. T cell growth factor receptors. Quantitation, specificity, and biological relevance. J Exp Med. 1981 Nov 1;154(5):1455–1474. doi: 10.1084/jem.154.5.1455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Shoyab M., De Larco J. E., Todaro G. J. Biologically active phorbol esters specifically alter affinity of epidermal growth factor membrane receptors. Nature. 1979 May 31;279(5712):387–391. doi: 10.1038/279387a0. [DOI] [PubMed] [Google Scholar]
  32. Smith K. A., Gilbride K. J., Favata M. F. Lymphocyte activating factor promotes T-cell growth factor production by cloned murine lymphoma cells. Nature. 1980 Oct 30;287(5785):853–855. doi: 10.1038/287853a0. [DOI] [PubMed] [Google Scholar]
  33. Smith K. A. Interleukin 2. Annu Rev Immunol. 1984;2:319–333. doi: 10.1146/annurev.iy.02.040184.001535. [DOI] [PubMed] [Google Scholar]
  34. Smith K. A., Lachman L. B., Oppenheim J. J., Favata M. F. The functional relationship of the interleukins. J Exp Med. 1980 Jun 1;151(6):1551–1556. doi: 10.1084/jem.151.6.1551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Sutter A., Riopelle R. J., Harris-Warrick R. M., Shooter E. M. Nerve growth factor receptors. Characterization of two distinct classes of binding sites on chick embryo sensory ganglia cells. J Biol Chem. 1979 Jul 10;254(13):5972–5982. [PubMed] [Google Scholar]
  36. Weissman A. M., Harford J. B., Svetlik P. B., Leonard W. L., Depper J. M., Waldmann T. A., Greene W. C., Klausner R. D. Only high-affinity receptors for interleukin 2 mediate internalization of ligand. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1463–1466. doi: 10.1073/pnas.83.5.1463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Williams J. M., Deloria D., Hansen J. A., Dinarello C. A., Loertscher R., Shapiro H. M., Strom T. B. The events of primary T cell activation can be staged by use of Sepharose-bound anti-T3 (64.1) monoclonal antibody and purified interleukin 1. J Immunol. 1985 Oct;135(4):2249–2255. [PubMed] [Google Scholar]
  38. Williams L. T., Tremble P. M., Lavin M. F., Sunday M. E. Platelet-derived growth factor receptors form a high affinity state in membrane preparations. Kinetics and affinity cross-linking studies. J Biol Chem. 1984 Apr 25;259(8):5287–5294. [PubMed] [Google Scholar]
  39. Zubler R. H., Erard F., Lees R. K., Van Laer M., Mingari C., Moretta L., MacDonald H. R. Mutant EL-4 thymoma cells polyclonally activate murine and human B cells via direct cell interaction. J Immunol. 1985 Jun;134(6):3662–3668. [PubMed] [Google Scholar]

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