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. 1986 Dec;83(23):9026–9029. doi: 10.1073/pnas.83.23.9026

Molecular basis for two different affinity states of the interleukin 2 receptor: affinity conversion model.

S Kondo, A Shimizu, Y Saito, M Kinoshita, T Honjo
PMCID: PMC387067  PMID: 3097640

Abstract

Two affinity species of the interleukin 2 (IL-2) receptor are different states of a single receptor molecule. We assumed that a binary complex between the IL-2 receptor and another lymphocyte-specific protein would constitute the high-affinity receptor. To test this assumption, we counted the numbers of IL-2 receptors with high and low affinity in a murine T-cell line CT/hR-1 that expresses not only murine but also human receptors by cDNA transfection. We found that human high-affinity receptors disappeared when the murine high-affinity receptors were already occupied by the ligand. The results were incompatible with a fixed number of human and murine receptors with high affinity in CT/hR-1 cells. We suggest that the high-affinity state of the IL-2 receptor is a ternary complex of IL-2, the IL-2 receptor, and a postulated "converter" protein, which is fewer in number than the receptors. The converter would be unable to form a complex with the IL-2 receptor unless IL-2 was already bound to it. The ligand binding to the receptor would cause a conformational change in the receptor, increasing its affinity to the converter. Ternary complex formation would, in turn, change the apparent affinity of the receptor to the ligand from low to high by reduction of the dissociation constant.

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Selected References

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

  1. Bolton A. E., Hunter W. M. The labelling of proteins to high specific radioactivities by conjugation to a 125I-containing acylating agent. Biochem J. 1973 Jul;133(3):529–539. doi: 10.1042/bj1330529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ceredig R., Lowenthal J. W., Nabholz M., MacDonald H. R. Expression of interleukin-2 receptors as a differentiation marker on intrathymic stem cells. Nature. 1985 Mar 7;314(6006):98–100. doi: 10.1038/314098a0. [DOI] [PubMed] [Google Scholar]
  3. Cosman D., Cerretti D. P., Larsen A., Park L., March C., Dower S., Gillis S., Urdal D. Cloning, sequence and expression of human interleukin-2 receptor. Nature. 1984 Dec 20;312(5996):768–771. doi: 10.1038/312768a0. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Greene W. C., Robb R. J., Svetlik P. B., Rusk C. M., Depper J. M., Leonard W. J. Stable expression of cDNA encoding the human interleukin 2 receptor in eukaryotic cells. J Exp Med. 1985 Jul 1;162(1):363–368. doi: 10.1084/jem.162.1.363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hatakeyama M., Minamoto S., Uchiyama T., Hardy R. R., Yamada G., Taniguchi T. Reconstitution of functional receptor for human interleukin-2 in mouse cells. Nature. 1985 Dec 5;318(6045):467–470. doi: 10.1038/318467a0. [DOI] [PubMed] [Google Scholar]
  7. Hemler M. E., Brenner M. B., McLean J. M., Strominger J. L. Antigenic stimulation regulates the level of expression of interleukin 2 receptor on human T cells. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2172–2175. doi: 10.1073/pnas.81.7.2172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kondo S., Shimizu A., Maeda M., Tagaya Y., Yodoi J., Honjo T. Expression of functional human interleukin-2 receptor in mouse T cells by cDNA transfection. Nature. 1986 Mar 6;320(6057):75–77. doi: 10.1038/320075a0. [DOI] [PubMed] [Google Scholar]
  9. Leonard W. J., Depper J. M., Crabtree G. R., Rudikoff S., Pumphrey J., Robb R. J., Krönke M., Svetlik P. B., Peffer N. J., Waldmann T. A. Molecular cloning and expression of cDNAs for the human interleukin-2 receptor. Nature. 1984 Oct 18;311(5987):626–631. doi: 10.1038/311626a0. [DOI] [PubMed] [Google Scholar]
  10. Maeda M., Shimizu A., Ikuta K., Okamoto H., Kashihara M., Uchiyama T., Honjo T., Yodoi J. Origin of human T-lymphotrophic virus I-positive T cell lines in adult T cell leukemia. Analysis of T cell receptor gene rearrangement. J Exp Med. 1985 Dec 1;162(6):2169–2174. doi: 10.1084/jem.162.6.2169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Malek T. R., Robb R. J., Shevach E. M. Identification and initial characterization of a rat monoclonal antibody reactive with the murine interleukin 2 receptor-ligand complex. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5694–5698. doi: 10.1073/pnas.80.18.5694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Miller J., Malek T. R., Leonard W. J., Greene W. C., Shevach E. M., Germain R. N. Nucleotide sequence and expression of a mouse interleukin 2 receptor cDNA. J Immunol. 1985 Jun;134(6):4212–4217. [PubMed] [Google Scholar]
  13. Morgan D. A., Ruscetti F. W., Gallo R. Selective in vitro growth of T lymphocytes from normal human bone marrows. Science. 1976 Sep 10;193(4257):1007–1008. doi: 10.1126/science.181845. [DOI] [PubMed] [Google Scholar]
  14. Nikaido T., Shimizu A., Ishida N., Sabe H., Teshigawara K., Maeda M., Uchiyama T., Yodoi J., Honjo T. Molecular cloning of cDNA encoding human interleukin-2 receptor. Nature. 1984 Oct 18;311(5987):631–635. doi: 10.1038/311631a0. [DOI] [PubMed] [Google Scholar]
  15. Osawa H., Diamantstein T. A rat monoclonal antibody that binds specifically to mouse T lymphoblasts and inhibits IL 2 receptor functions: a putative anti-IL 2 receptor antibody. J Immunol. 1984 May;132(5):2445–2450. [PubMed] [Google Scholar]
  16. Robb R. J. Conversion of low-affinity interleukin 2 receptors to a high-affinity state following fusion of cell membranes. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3992–3996. doi: 10.1073/pnas.83.11.3992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. Sabe H., Kondo S., Shimizu A., Tagaya Y., Yodoi J., Kobayashi N., Hatanaka M., Matsunami N., Maeda M., Noma T. Properties of human interleukin-2 receptors expressed on non-lymphoid cells by cDNA transfection. Mol Biol Med. 1984 Dec;2(6):379–396. [PubMed] [Google Scholar]
  20. Shimuzu A., Kondo S., Takeda S., Yodoi J., Ishida N., Sabe H., Osawa H., Diamantstein T., Nikaido T., Honjo T. Nucleotide sequence of mouse IL-2 receptor cDNA and its comparison with the human IL-2 receptor sequence. Nucleic Acids Res. 1985 Mar 11;13(5):1505–1516. doi: 10.1093/nar/13.5.1505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Smith K. A. T-cell growth factor. Immunol Rev. 1980;51:337–357. doi: 10.1111/j.1600-065x.1980.tb00327.x. [DOI] [PubMed] [Google Scholar]
  22. Tanaka Y., Tozawa H., Hayami M., Sugamura K., Hinuma Y. Distinct reactivities of four monoclonal antibodies with human interleukin 2 receptor. Microbiol Immunol. 1985;29(10):959–972. doi: 10.1111/j.1348-0421.1985.tb02960.x. [DOI] [PubMed] [Google Scholar]
  23. Uchiyama T., Broder S., Waldmann T. A. A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. I. Production of anti-Tac monoclonal antibody and distribution of Tac (+) cells. J Immunol. 1981 Apr;126(4):1393–1397. [PubMed] [Google Scholar]
  24. Yachie A., Miyawaki T., Uwadana N., Ohzeki S., Taniguchi N. Sequential expression of T cell activation (Tac) antigen and Ia determinants on circulating human T cells after immunization with tetanus toxoid. J Immunol. 1983 Aug;131(2):731–735. [PubMed] [Google Scholar]

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