Advertisement

Molecular Analysis of the Interleukin-2 Receptor Complex: Expression of the Human α and β Chain cDNAs

  • T. Taniguchi
  • M. Hatakeyama
  • S. Minamoto
  • T. Kono
  • T. Doi
  • M. Tsudo
  • M. Miyasaka
Conference paper

Abstract

Lymphokines, a class of soluble mediators for intercellular communications are known to play a key role in the regulation of the immune system through interaction with specific receptor(s) on the target cells. Interleukin-2 (IL-2), the first of a series of lymphokines to be discovered and completely characterized, plays a key role in the antigen-specific clonal proliferation of T lymphocytes (T cells). Expression of IL-2 and functional, high-affinity IL-2 receptor (IL-2R) complex is induced in the antigen-activated T cells. IL-2 also acts on other cell types such as B lymphocytes (B cells), macrophages, natural killer cells (NK cells), immature thymocytes and neural cells such as oligodendrocytes (for reviews, see Smith, 1984, 1988; Taniguchi et al., 1986; Merrill, 1987). To date, little has been known about the mechanism(s) of signal transduction in the IL-2 system. The receptor for IL-2 is unique in that the ligand binds to at least two distinct membrane components, giving rise to the expression of high-, intermediate- and low-affinity IL-2R forms with the respective dissociation constants (Kds) of about 10-11M, 10-9M and 10-8M (Robb et al., 1984; Smith, 1988). Following the initial expression studies for the clones human IL-2Rα cDNA, it became evident that IL-2Rα constitutes the low-affinity form and it participates in the formation of the functional, high-affinity IL-2R in association with a specific membrane component(s) of lymphoid cells (Hatakeyama et al., 1985; Kondo et al., 1986; Robb, 1986). Subsequently, such a component was identified to be a novel IL-2 receptor chain, termed IL-2Rβ chain (IL- 2Rβ or p70–75) (Sharon et al., 1986; Tsudo et al., 1986; Teshigawara et al., 1987; Dukovich et al., 1987). Thus the two IL-2R components, the α and β chain, form the heterodimeric high-affinity IL-2R via noncovalent interactions, whereas the β chain alone constitutes the intermediate-affinity IL-2R. Experimental evidence suggests that IL- 2Rβ chain is the main component in driving the IL-2-mediated signal transduction (for review, see Smith, 1988). As an essential step to gain further insight on the molecular basis of the functional (i.e. high-affinity) IL-2R and on the mechanism of IL-2 mediated signal transduction, we have isolated the cDNAs encoding the human IL-2Rβ chain.

Keywords

Cytoplasmic Region Immature Thymocyte Chain cDNA Transformant Clone National Biomedical Research Foundation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Collins, L., W.-H. Tsien, C. Seals, J. Hakimi, D. Weber, P. Bailon, J. Hoskings, W.C. Greene, V. Toome, and G. Ju.(1988). Identification of specific residues of human interleukin-2 that affect binding to the 70-kDa subunit(p70) of the interleukin-2 receptor. Proc. Natl. Acad. Sci. 85: 7709–7713.PubMedCentralPubMedCrossRefGoogle Scholar
  2. Cosman, D., D.P. Cerretti, A. Larsen, L. Park, C. March, S. Dower, S. Gillis, and D. Urdall (1984). Cloning, sequence and expression of human interleukin-2 receptor. Nature 312: 768–771.PubMedCrossRefGoogle Scholar
  3. Dukovich, M., Y. Wano, J.B. Thuy, P. Katz, B.R. Cullen, J.H. Kehr, and W.C. Greene (1987). A second human interleukin-2 binding protein that may be a component of high-affinity interleukin-2 receptors. Nature 327: 518–522.PubMedCrossRefGoogle Scholar
  4. Hatakeyama, M., S. Minamoto, T. Uchiyama, R.R. Hardy, G. Yamada, and T. Taniguchi (1985). Reconstitution of functional receptor for human interleukin-2 in mouse cells. Nature 318: 467–470PubMedCrossRefGoogle Scholar
  5. Hatakeyama, M., M. Tsudo, S. Minamoto, T. Kono, T. Doi, T. Miyata, M. Miyasaka, and T. Taniguchi (1989). Interleukin-2 receptor β chain gene: Generation of three receptor forms by cloned human α and β chain cDNA’s. Science 244: 551–556.PubMedCrossRefGoogle Scholar
  6. Kondoh, S., A. Shimizu, M. Maeda, Y. Tagaya, J. Yodoi, and T. Honjo (1986). Expression of functional human interleukin-2 receptor in mouse T cells by cDNA transfection. Nature 320: 75–77.CrossRefGoogle Scholar
  7. Leonard, W.J., J.M. Depper, G.R. Crabtree, S. Rudikoff, J. Pumphrey, R.J. Robb, M. Kronke, P.B. Svetlik, N.J. Peffer, T.A. Waldmann, and W.C. Greene (1984). Molecular cloning and expression of cDNAs for the human interleukin-2 receptor. Nature 311: 626–631.PubMedCrossRefGoogle Scholar
  8. Merrill, J.E. (1987). Macroglia: neural cells responsive to lymphokines and growth factors. Immunol. Today 8: 146–150.CrossRefGoogle Scholar
  9. Nikaido, T., A. Shimizu, N. Ishida, H. Sabe, K. Teshigawara, M. Maeda, T. Uchiyama, J. Yodoi, and T. Honjo (1984). Molecular cloning of cDNA encoding human interleukin-2 receptor. Nature 311: 631–635.PubMedCrossRefGoogle Scholar
  10. Robb, R.J. (1986). Conversion of low-affinity interleukin-2 receptors to a high-affinity state following fusion of cell membranes. Proc. Natl. Acad. Sci. 83: 3992–3996.PubMedCentralPubMedCrossRefGoogle Scholar
  11. Robb, R.J., W.C. Greene, and C.M. Rusk (1984). Low and high affinity cellular receptors for interleukin-2. Implications for the level of Tac antigen. J. Exp. Med. 154: 1455–1474.CrossRefGoogle Scholar
  12. Seed, B. (1987). An LFA-3 cDNA encodes a phospholipid-linked membrane protein homologous to its receptor CD2. Nature 329: 840–842.PubMedCrossRefGoogle Scholar
  13. Seed, B., and A. Aruffo (1987). Molecular cloning of the CD2 antigen, the T-cell erythrocyte receptor, by a rapid immunoselection procedure. Proc. Natl. Acad. Sci. 84: 3365–3369.PubMedCentralPubMedCrossRefGoogle Scholar
  14. Sharon, M., R.D. Klausner, B.R. Culler, R. Chizzonite, and W.J. Leonard (1986). Novel interleukin-2 receptor subunit detected by crosslinking under high-affinity conditions. Science 234: 859–863.PubMedCrossRefGoogle Scholar
  15. Smith, K.A. (1984). Interleukin-2. Ann.Rev.Immunol. 2: 319–333.CrossRefGoogle Scholar
  16. Smith, K.A. (1988). Interleukin-2: Inception, impact and implications. Science 240: 1169–1176.PubMedCrossRefGoogle Scholar
  17. Taniguchi, T., H. Matsui, T. Fujita, C. Takaoka, N. Kashima, R. Yoshimoto, and J. Hamuro (1983). Structure and expression of a cloned cDNA for human interleukin-2. Nature 302: 305–310.PubMedCrossRefGoogle Scholar
  18. Taniguchi, T., H. Matsui, T. Fujita, M. Hatakeyama, N. Kashima, A. Fuse, J. Hamuro, C. Nishi-Takaoka, and G. Yamada (1986). Molecular analysis of the interleukin-2 system. Immunol. Rev. 92: 121–133.PubMedCrossRefGoogle Scholar
  19. Taniguchi, T. (1988). Regulation of cytokine gene expression. Ann. Rev.Immunol. 6: 439–464.CrossRefGoogle Scholar
  20. Teshigawara, K., H-M. Wang, K. Kato, and K.A. Smith (1987). Interleukin-2 high-affinity receptor expression requires two distinct binding proteins. J. Exp. Med. 165: 223–238.PubMedCrossRefGoogle Scholar
  21. Tsudo, M., R.W. Kozak, C.K. Goldman, and T.A. Waldmann (1986). Demonstration of a non-Tac peptide that binds interleukin-2: a potential participant in a multi-chain interleukin-2 receptor complex. Proc. Natl. Acad. Sci. 83: 9694–9698.PubMedCentralPubMedCrossRefGoogle Scholar
  22. Tsudo, M., F. Kitamura, and M. Miyasaka (1989). Characterization of the interleukin-2 receptor p chain using three distinct monoclonal antibodies. Proc. Natl. Acad. Sci. 86: 1982–1986.PubMedCentralPubMedCrossRefGoogle Scholar
  23. Yodoi, J., K. Teshigawara, T. Nikaido, K. Fukui, T. Noma, T. Honjo, M. Takigawa, M. Sasaki, N. Minato, M. Tsudo, T. Uchiyama, and M. Maeda (1986) TCGF(IL-2)-receptor inducing factor(s): I.Regulation of IL-2 receptor on a natural killer-like cell line(YT cells). J.Immunol. 134: 1623–1630.Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • T. Taniguchi
  • M. Hatakeyama
  • S. Minamoto
  • T. Kono
  • T. Doi
  • M. Tsudo
  • M. Miyasaka

There are no affiliations available

Personalised recommendations