Abstract
Interleukin-2 (IL-2) has a key role in the antigen-specific clonal growth of T lymphocytes, by virtue of its interaction with a specific cell-surface receptor (IL-2R)1–4. The growth signal seems to be delivered by IL-2 bound to the high-affinity, but not the low-affinity, receptor5,6. Genes encoding IL-2 (refs 7–13) and its receptor (that is, Tac-antigen)14–17 have been cloned and analysed in detail. We have now achieved cell-type-specific reconstitution of the high-affinity human IL-2R by expressing the complementary DNA cloned from normal lymphocytes. A mouse T-lymphocytic line, EL-4, expressed human IL-2R with high (dissociation constant (Kd) = 160–220 pM) and low (Kd = 2.1–2.2 nM) affinity for recombinant human IL-2, while mouse L929 cells expressed only a single class of the IL-2R with lower affinity (Kd = 34.5 nM) for the ligand. We also show that the human IL-2R expressed in EL-4 cells responds to IL-2 and mediates reversed signal transduction: growth of the EL-4 cells harbouring the IL-2 R is inhibited specifically by human recombinant IL-2. The approach described here may provide a general experimental framework for elucidating the molecular basis of signal transduction mediated by specific receptor–ligand interaction.
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References
Smith, K. A. A. Rev. Immun. 2, 319–334 (1984).
Robb, R. J., Munck, A. & Smith, K. A. J. exp. Med. 154, 1455–1474 (1981).
Cantrell, D. A. & Smith, K. A. J. exp. Med. 158, 1895–1911 (1983).
Smith, K. A. & Cantrell, D. A. Proc. natn. Acad. Sci. U.S.A. 82, 864–868 (1985).
Robb, R. J., Greene, W. C. & Rusk, C. M. J. exp. Med. 160, 1126–1146 (1984).
Uchiyama, T. et al. J. clin. Invest. 76, 446–453 (1985).
Taniguchi, T. et al. Nature 302, 305–310 (1983).
Holbrook, N. J. et al. Proc. natn. Acad. Sci. U.S.A. 81, 1634–1638 (1984).
Devos, R. et al. Nucleic Acids Res. 11, 4307–4323 (1983).
Fujita, T., Takaoka, C., Matsui, H. & Taniguchi, T. Proc. natn. Acad. Sci. U.S.A. 80, 7437–7441 (1983).
Kashima, N. et al. Nature 313, 402–404 (1985).
Yokota, T. et al. Proc. natn. Acad. Sci. U.S.A. 82, 68–72 (1985).
Fuse, A. et al. Nucleic Acids Res. 12, 9323–9331 (1984).
Leonard, W. J. et al. Nature 311, 626–631 (1984).
Nikaido, T. et al. Nature 311, 631–635 (1984).
Cosman, D. et al. Nature 312, 768–771 (1984).
Shimizu, A. et al. Nucleic Acids Res. 13, 1505–1516 (1985).
Taniguchi, T., Pang, R. H. L., Yip, Y. K., Henriksen, D. & Vilcek, J. Proc. natn. Acad. Sci. U.S.A. 78, 3469–3472 (1981).
Uchiyama, T., Broder, S. & Waldmann, T. A. J. Immun. 126, 1393–1397 (1981).
Uchiyama, T., Nelson, D. L., Fleischer, T. A. & Waldmann, T. A. J. Immun. 126, 1398–1403 (1981).
Gorman, C. M., Merlino, G. T., Willingham, M. C., Pastan, I. & Howard, B. H., Proc. Natn. Acad. Sci. U.S.A. 79, 6777–6781 (1982).
Mulligan, R. C. & Berg, P. Science 209, 1422–1427 (1980).
Farrar, J. J. et al. Immun. Rev. 63, 129–166 (1982).
Gillis, S., Perm, M. M., Ou, W. & Smith, K. A. J. Immun. 120, 2027–2032 (1978).
Osawa, H. & Diamantstein, T. J. Immun. 132, 2445–2450 (1984).
Gill, G. N. & Lazar, C. S. Nature 293, 305–307 (1981).
Buss, J. E., Kudlow, J. E., Lazar, C. S. & Gill, G. N. Proc. natn. Acad. Sci. U.S.A. 79, 2574–2578 (1982).
Roberts, A. B. et al. Proc. natn. Acad. Sci. U.S.A. 82, 119–123 (1985).
Sugamura, K., Nakai, S., Fujii, M. & Hinuma, Y. J. exp. Med. 161, 1243–1248 (1985).
Farrar, W. L. & Anderson, W. B. Nature 315, 233–235 (1985).
Greene, W. C. et al. J. exp. Med. 162, 363–368 (1985).
Oi, V. T., Morrison, S. L., Herzenberg, L. A. & Berg, P. Proc. natn. Acad. Sci. U.S.A. 80, 825–829 (1983).
Chu, G. & Sharp, P. Gene 13, 197–202 (1981).
Parks, D. R., Bryan, V. M., Oi, V. T. & Herzenberg, L. A. Proc. natn. Acad. Sci. U.S.A. 76, 1962–1966 (1979).
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Hatakeyama, M., Minamoto, S., Uchiyama, T. et al. Reconstitution of functional receptor for human interleukin-2 in mouse cells. Nature 318, 467–470 (1985). https://doi.org/10.1038/318467a0
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DOI: https://doi.org/10.1038/318467a0
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