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Abstract 


We have recently cloned a novel cytokine, IL-15, with shared bioactivities but no sequence homology with IL-2. We found high affinity IL-15 binding to many cell types, including cells of non-lymphoid origin. Analysis of IL-15 interaction with subunits of the IL-2 receptor (IL-2R) revealed that the alpha subunit was not involved in IL-15 binding. We demonstrated directly in cells transfected with IL-2R subunits that both the beta and gamma chains are required for IL-15 binding and signaling. Hence, IL-15, like IL-2, IL-4 and IL-7, utilizes the common IL-2R gamma subunit found to be defective in X-linked severe combined immunodeficiency in humans. IL-15 is the only cytokine other than IL-2 that has also been shown to share the beta signaling subunit of IL-2R. The differential ability of some cells to bind and respond to IL-2 and IL-15 implies the existence of an additional IL-15-specific component.

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EMBO J. 1994 Jun 15; 13(12): 2822–2830.
PMCID: PMC395163
PMID: 8026467

Utilization of the beta and gamma chains of the IL-2 receptor by the novel cytokine IL-15.

Abstract

We have recently cloned a novel cytokine, IL-15, with shared bioactivities but no sequence homology with IL-2. We found high affinity IL-15 binding to many cell types, including cells of non-lymphoid origin. Analysis of IL-15 interaction with subunits of the IL-2 receptor (IL-2R) revealed that the alpha subunit was not involved in IL-15 binding. We demonstrated directly in cells transfected with IL-2R subunits that both the beta and gamma chains are required for IL-15 binding and signaling. Hence, IL-15, like IL-2, IL-4 and IL-7, utilizes the common IL-2R gamma subunit found to be defective in X-linked severe combined immunodeficiency in humans. IL-15 is the only cytokine other than IL-2 that has also been shown to share the beta signaling subunit of IL-2R. The differential ability of some cells to bind and respond to IL-2 and IL-15 implies the existence of an additional IL-15-specific component.

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  • Arima N, Kamio M, Imada K, Hori T, Hattori T, Tsudo M, Okuma M, Uchiyama T. Pseudo-high affinity interleukin 2 (IL-2) receptor lacks the third component that is essential for functional IL-2 binding and signaling. J Exp Med. 1992 Nov 1;176(5):1265–1272. [Europe PMC free article] [Abstract] [Google Scholar]
  • Asao H, Takeshita T, Ishii N, Kumaki S, Nakamura M, Sugamura K. Reconstitution of functional interleukin 2 receptor complexes on fibroblastoid cells: involvement of the cytoplasmic domain of the gamma chain in two distinct signaling pathways. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4127–4131. [Europe PMC free article] [Abstract] [Google Scholar]
  • Bazan JF. Unraveling the structure of IL-2. Science. 1992 Jul 17;257(5068):410–413. [Abstract] [Google Scholar]
  • Cosman D. The hematopoietin receptor superfamily. Cytokine. 1993 Mar;5(2):95–106. [Abstract] [Google Scholar]
  • Cosman D, Cerretti DP, 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. [Abstract] [Google Scholar]
  • D'Andrea AD, Fasman GD, Lodish HF. Erythropoietin receptor and interleukin-2 receptor beta chain: a new receptor family. Cell. 1989 Sep 22;58(6):1023–1024. [Abstract] [Google Scholar]
  • Dower SK, Ozato K, Segal DM. The interaction of monoclonal antibodies with MHC class I antigens on mouse spleen cells. I. Analysis of the mechanism of binding. J Immunol. 1984 Feb;132(2):751–758. [Abstract] [Google Scholar]
  • Dower SK, Hefeneider SH, Alpert AR, Urdal DL. Quantitative measurement of human interleukin 2 receptor levels with intact and detergent-solubilized human T-cells. Mol Immunol. 1985 Aug;22(8):937–947. [Abstract] [Google Scholar]
  • Gillis S, Smith KA. Long term culture of tumour-specific cytotoxic T cells. Nature. 1977 Jul 14;268(5616):154–156. [Abstract] [Google Scholar]
  • Grabstein K, Eisenman J, Mochizuki D, Shanebeck K, Conlon P, Hopp T, March C, Gillis S. Purification to homogeneity of B cell stimulating factor. A molecule that stimulates proliferation of multiple lymphokine-dependent cell lines. J Exp Med. 1986 Jun 1;163(6):1405–1414. [Europe PMC free article] [Abstract] [Google Scholar]
  • Grabstein KH, Maliszewski CR, Shanebeck K, Sato TA, Spriggs MK, Fanslow WC, Armitage RJ. The regulation of T cell-dependent antibody formation in vitro by CD40 ligand and IL-2. J Immunol. 1993 Apr 15;150(8 Pt 1):3141–3147. [Abstract] [Google Scholar]
  • Hatakeyama M, Mori H, Doi T, Taniguchi T. A restricted cytoplasmic region of IL-2 receptor beta chain is essential for growth signal transduction but not for ligand binding and internalization. Cell. 1989 Dec 1;59(5):837–845. [Abstract] [Google Scholar]
  • Hatakeyama M, Tsudo M, Minamoto S, Kono T, Doi T, Miyata T, Miyasaka M, Taniguchi T. Interleukin-2 receptor beta chain gene: generation of three receptor forms by cloned human alpha and beta chain cDNA's. Science. 1989 May 5;244(4904):551–556. [Abstract] [Google Scholar]
  • Hatakeyama M, Kawahara A, Mori H, Shibuya H, Taniguchi T. c-fos gene induction by interleukin 2: identification of the critical cytoplasmic regions within the interleukin 2 receptor beta chain. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2022–2026. [Europe PMC free article] [Abstract] [Google Scholar]
  • Kondo M, Takeshita T, Ishii N, Nakamura M, Watanabe S, Arai K, Sugamura K. Sharing of the interleukin-2 (IL-2) receptor gamma chain between receptors for IL-2 and IL-4. Science. 1993 Dec 17;262(5141):1874–1877. [Abstract] [Google Scholar]
  • Kumaki S, Kondo M, Takeshita T, Asao H, Nakamura M, Sugamura K. Cloning of the mouse interleukin 2 receptor gamma chain: demonstration of functional differences between the mouse and human receptors. Biochem Biophys Res Commun. 1993 May 28;193(1):356–363. [Abstract] [Google Scholar]
  • Kündig TM, Schorle H, Bachmann MF, Hengartner H, Zinkernagel RM, Horak I. Immune responses in interleukin-2-deficient mice. Science. 1993 Nov 12;262(5136):1059–1061. [Abstract] [Google Scholar]
  • Larsen A, Davis T, Curtis BM, Gimpel S, Sims JE, Cosman D, Park L, Sorensen E, March CJ, Smith CA. Expression cloning of a human granulocyte colony-stimulating factor receptor: a structural mosaic of hematopoietin receptor, immunoglobulin, and fibronectin domains. J Exp Med. 1990 Dec 1;172(6):1559–1570. [Europe PMC free article] [Abstract] [Google Scholar]
  • McMahan CJ, Slack JL, Mosley B, Cosman D, Lupton SD, Brunton LL, Grubin CE, Wignall JM, Jenkins NA, Brannan CI, et al. A novel IL-1 receptor, cloned from B cells by mammalian expression, is expressed in many cell types. EMBO J. 1991 Oct;10(10):2821–2832. [Europe PMC free article] [Abstract] [Google Scholar]
  • Miyajima A, Kitamura T, Harada N, Yokota T, Arai K. Cytokine receptors and signal transduction. Annu Rev Immunol. 1992;10:295–331. [Abstract] [Google Scholar]
  • Mosley B, Beckmann MP, March CJ, Idzerda RL, Gimpel SD, VandenBos T, Friend D, Alpert A, Anderson D, Jackson J, et al. The murine interleukin-4 receptor: molecular cloning and characterization of secreted and membrane bound forms. Cell. 1989 Oct 20;59(2):335–348. [Abstract] [Google Scholar]
  • Noguchi M, Nakamura Y, Russell SM, Ziegler SF, Tsang M, Cao X, Leonard WJ. Interleukin-2 receptor gamma chain: a functional component of the interleukin-7 receptor. Science. 1993 Dec 17;262(5141):1877–1880. [Abstract] [Google Scholar]
  • Noguchi M, Yi H, Rosenblatt HM, Filipovich AH, Adelstein S, Modi WS, McBride OW, Leonard WJ. Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans. Cell. 1993 Apr 9;73(1):147–157. [Abstract] [Google Scholar]
  • Park LS, Friend DJ, Schmierer AE, Dower SK, Namen AE. Murine interleukin 7 (IL-7) receptor. Characterization on an IL-7-dependent cell line. J Exp Med. 1990 Apr 1;171(4):1073–1089. [Europe PMC free article] [Abstract] [Google Scholar]
  • Robb RJ, Greene WC. Internalization of interleukin 2 is mediated by the beta chain of the high-affinity interleukin 2 receptor. J Exp Med. 1987 Apr 1;165(4):1201–1206. [Europe PMC free article] [Abstract] [Google Scholar]
  • Robb RJ, Greene WC, Rusk CM. 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. [Europe PMC free article] [Abstract] [Google Scholar]
  • Roehm NW, Rodgers GH, Hatfield SM, Glasebrook AL. An improved colorimetric assay for cell proliferation and viability utilizing the tetrazolium salt XTT. J Immunol Methods. 1991 Sep 13;142(2):257–265. [Abstract] [Google Scholar]
  • Russell SM, Keegan AD, Harada N, Nakamura Y, Noguchi M, Leland P, Friedmann MC, Miyajima A, Puri RK, Paul WE, et al. Interleukin-2 receptor gamma chain: a functional component of the interleukin-4 receptor. Science. 1993 Dec 17;262(5141):1880–1883. [Abstract] [Google Scholar]
  • Schorle H, Holtschke T, Hünig T, Schimpl A, Horak I. Development and function of T cells in mice rendered interleukin-2 deficient by gene targeting. Nature. 1991 Aug 15;352(6336):621–624. [Abstract] [Google Scholar]
  • Sharon M, Klausner RD, Cullen BR, Chizzonite R, Leonard WJ. Novel interleukin-2 receptor subunit detected by cross-linking under high-affinity conditions. Science. 1986 Nov 14;234(4778):859–863. [Abstract] [Google Scholar]
  • Sims JE, Acres RB, Grubin CE, McMahan CJ, Wignall JM, March CJ, Dower SK. Cloning the interleukin 1 receptor from human T cells. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8946–8950. [Europe PMC free article] [Abstract] [Google Scholar]
  • Suzuki J, Takeshita T, Ohbo K, Asao H, Tada K, Sugamura K. IL-2 receptor subunit, p75: direct demonstration of its IL-2 binding ability by using a novel monoclonal antibody. Int Immunol. 1989;1(4):373–377. [Abstract] [Google Scholar]
  • Takeshita T, Asao H, Ohtani K, Ishii N, Kumaki S, Tanaka N, Munakata H, Nakamura M, Sugamura K. Cloning of the gamma chain of the human IL-2 receptor. Science. 1992 Jul 17;257(5068):379–382. [Abstract] [Google Scholar]
  • Takeshita T, Ohtani K, Asao H, Kumaki S, Nakamura M, Sugamura K. An associated molecule, p64, with IL-2 receptor beta chain. Its possible involvement in the formation of the functional intermediate-affinity IL-2 receptor complex. J Immunol. 1992 Apr 1;148(7):2154–2158. [Abstract] [Google Scholar]
  • Taniguchi T, Minami Y. The IL-2/IL-2 receptor system: a current overview. Cell. 1993 Apr 9;73(1):5–8. [Abstract] [Google Scholar]
  • Tsudo M, Kitamura F, Miyasaka M. Characterization of the interleukin 2 receptor beta chain using three distinct monoclonal antibodies. Proc Natl Acad Sci U S A. 1989 Mar;86(6):1982–1986. [Europe PMC free article] [Abstract] [Google Scholar]
  • Voss SD, Sondel PM, Robb RJ. Characterization of the interleukin 2 receptors (IL-2R) expressed on human natural killer cells activated in vivo by IL-2: association of the p64 IL-2R gamma chain with the IL-2R beta chain in functional intermediate-affinity IL-2R. J Exp Med. 1992 Aug 1;176(2):531–541. [Europe PMC free article] [Abstract] [Google Scholar]
  • Weinberg K, Parkman R. Severe combined immunodeficiency due to a specific defect in the production of interleukin-2. N Engl J Med. 1990 Jun 14;322(24):1718–1723. [Abstract] [Google Scholar]
  • Yodoi J, Teshigawara K, Nikaido T, Fukui K, Noma T, Honjo T, Takigawa M, Sasaki M, Minato N, Tsudo M, et al. TCGF (IL 2)-receptor inducing factor(s). I. Regulation of IL 2 receptor on a natural killer-like cell line (YT cells). J Immunol. 1985 Mar;134(3):1623–1630. [Abstract] [Google Scholar]

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