Skip to main content
Immunology logoLink to Immunology
. 1997 May;91(1):28–34. doi: 10.1046/j.1365-2567.1997.00236.x

Altered interleukin-2 receptor alpha-chain is expressed in human T-cell leukaemia virus type-I-infected T-cell lines and human peripheral blood mononuclear cells of adult T-cell leukaemia patients through an alternative splicing mechanism.

S Horiuchi 1, Y Koyanagi 1, Y Tanaka 1, M Waki 1, A Matsumoto 1, Y W Zhou 1, M Yamamoto 1, N Yamamoto 1
PMCID: PMC1364031  PMID: 9203962

Abstract

A polymerase chain reaction (PCR) method was used to detect the interleukin-2 receptor alpha-chain (IL-2R alpha) chain which lacks the conventional transmembrane (TM) domain in mRNA from human T-cell leukaemia virus type-I (HTLV-I)-infected cell lines or peripheral blood mononuclear cells (PBMC) isolated from adult T-cell leukaemia (ATL) patients. Primer pairs encompassing the TM domain were selected to generate a 357-base pair (bp) fragment. A 146-bp PCR product was observed consistently in addition to the target 357-bp PCR product in mRNA from HTLV-I-infected cell lines, such as MT-1, MT-2, MT-4 and in PBMC isolated from ATL patients. However, this 146-bp PCR product was undetectable in HTLV-I-negative cell lines. The product was also detected in PBMC from normal individuals if activated in vitro with phytohaemagglutinin but not without stimulation. DNA sequence analyses revealed that exons from 5 to 7, which define a 211-bp region containing the conventional TM domain, were deleted in the 146-bp PCR product. The C-terminal amino acid sequence starting from Gly174 of the 211-bp-deleted molecule was distinct from that of conventional IL-2R alpha as a result of an altered reading frame. We identified a 45000 MW peptide generated from IL-2R alpha mRNA through this exon skip in cell lysate of MT-1 and MT-2 by Western blot analyses using an antibody raised against the peptides specific to an altered IL-2R alpha. Our results indicate that an altered IL-2R alpha chain is expressed in HTLV-I-infected T lymphocytic cell lines and in ATL patients.

Full text

PDF
28

Images in this article

Selected References

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

  1. Arrigo S. J., Weitsman S., Rosenblatt J. D., Chen I. S. Analysis of rev gene function on human immunodeficiency virus type 1 replication in lymphoid cells by using a quantitative polymerase chain reaction method. J Virol. 1989 Nov;63(11):4875–4881. doi: 10.1128/jvi.63.11.4875-4881.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Goodwin R. G., Friend D., Ziegler S. F., Jerzy R., Falk B. A., Gimpel S., Cosman D., Dower S. K., March C. J., Namen A. E. Cloning of the human and murine interleukin-7 receptors: demonstration of a soluble form and homology to a new receptor superfamily. Cell. 1990 Mar 23;60(6):941–951. doi: 10.1016/0092-8674(90)90342-c. [DOI] [PubMed] [Google Scholar]
  3. Hirano T., Taga T., Yasukawa K., Nakajima K., Nakano N., Takatsuki F., Shimizu M., Murashima A., Tsunasawa S., Sakiyama F. Human B-cell differentiation factor defined by an anti-peptide antibody and its possible role in autoantibody production. Proc Natl Acad Sci U S A. 1987 Jan;84(1):228–231. doi: 10.1073/pnas.84.1.228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Honda M., Kitamura K., Matsuda K., Yokota Y., Yamamoto N., Mitsuyasu R., Chermann J. C., Tokunaga T. Soluble IL-2 receptor in AIDS. Correlation of its serum level with the classification of HIV-induced diseases and its characterization. J Immunol. 1989 Jun 15;142(12):4248–4255. [PubMed] [Google Scholar]
  5. Horiuchi S., Koyanagi Y., Zhou Y., Miyamoto H., Tanaka Y., Waki M., Matsumoto A., Yamamoto M., Yamamoto N. Soluble interleukin-6 receptors released from T cell or granulocyte/macrophage cell lines and human peripheral blood mononuclear cells are generated through an alternative splicing mechanism. Eur J Immunol. 1994 Aug;24(8):1945–1948. doi: 10.1002/eji.1830240837. [DOI] [PubMed] [Google Scholar]
  6. Inoue J., Seiki M., Taniguchi T., Tsuru S., Yoshida M. Induction of interleukin 2 receptor gene expression by p40x encoded by human T-cell leukemia virus type 1. EMBO J. 1986 Nov;5(11):2883–2888. doi: 10.1002/j.1460-2075.1986.tb04583.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kalyanaraman V. S., Sarngadharan M. G., Nakao Y., Ito Y., Aoki T., Gallo R. C. Natural antibodies to the structural core protein (p24) of the human T-cell leukemia (lymphoma) retrovirus found in sera of leukemia patients in Japan. Proc Natl Acad Sci U S A. 1982 Mar;79(5):1653–1657. doi: 10.1073/pnas.79.5.1653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
  9. Leonard W. J., Depper J. M., Kanehisa M., Krönke M., Peffer N. J., Svetlik P. B., Sullivan M., Greene W. C. Structure of the human interleukin-2 receptor gene. Science. 1985 Nov 8;230(4726):633–639. doi: 10.1126/science.2996141. [DOI] [PubMed] [Google Scholar]
  10. Maniatis T. Mechanisms of alternative pre-mRNA splicing. Science. 1991 Jan 4;251(4989):33–34. doi: 10.1126/science.1824726. [DOI] [PubMed] [Google Scholar]
  11. Marcon L., Fritz M. E., Kurman C. C., Jensen J. C., Nelson D. L. Soluble Tac peptide is present in the urine of normal individuals and at elevated levels in patients with adult T cell leukaemia (ATL). Clin Exp Immunol. 1988 Jul;73(1):29–33. [PMC free article] [PubMed] [Google Scholar]
  12. Maruyama M., Shibuya H., Harada H., Hatakeyama M., Seiki M., Fujita T., Inoue J., Yoshida M., Taniguchi T. Evidence for aberrant activation of the interleukin-2 autocrine loop by HTLV-1-encoded p40x and T3/Ti complex triggering. Cell. 1987 Jan 30;48(2):343–350. doi: 10.1016/0092-8674(87)90437-5. [DOI] [PubMed] [Google Scholar]
  13. Mattox W., Ryner L., Baker B. S. Autoregulation and multifunctionality among trans-acting factors that regulate alternative pre-mRNA processing. J Biol Chem. 1992 Sep 25;267(27):19023–19026. [PubMed] [Google Scholar]
  14. Mosley B., Beckmann M. P., March C. J., Idzerda R. L., Gimpel S. D., VandenBos T., Friend D., Alpert A., Anderson D., Jackson J. The murine interleukin-4 receptor: molecular cloning and characterization of secreted and membrane bound forms. Cell. 1989 Oct 20;59(2):335–348. doi: 10.1016/0092-8674(89)90295-x. [DOI] [PubMed] [Google Scholar]
  15. Müllberg J., Oberthür W., Lottspeich F., Mehl E., Dittrich E., Graeve L., Heinrich P. C., Rose-John S. The soluble human IL-6 receptor. Mutational characterization of the proteolytic cleavage site. J Immunol. 1994 May 15;152(10):4958–4968. [PubMed] [Google Scholar]
  16. 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]
  17. Novick D., Engelmann H., Wallach D., Rubinstein M. Soluble cytokine receptors are present in normal human urine. J Exp Med. 1989 Oct 1;170(4):1409–1414. doi: 10.1084/jem.170.4.1409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Robb R. J., Kutny R. M. Structure-function relationships for the IL 2-receptor system. IV. Analysis of the sequence and ligand-binding properties of soluble Tac protein. J Immunol. 1987 Aug 1;139(3):855–862. [PubMed] [Google Scholar]
  19. Rubin L. A., Kurman C. C., Fritz M. E., Biddison W. E., Boutin B., Yarchoan R., Nelson D. L. Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro. J Immunol. 1985 Nov;135(5):3172–3177. [PubMed] [Google Scholar]
  20. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  21. Symons J. A., Wood N. C., Di Giovine F. S., Duff G. W. Soluble IL-2 receptor in rheumatoid arthritis. Correlation with disease activity, IL-1 and IL-2 inhibition. J Immunol. 1988 Oct 15;141(8):2612–2618. [PubMed] [Google Scholar]
  22. Tanaka Y., Zeng L., Shiraki H., Shida H., Tozawa H. Identification of a neutralization epitope on the envelope gp46 antigen of human T cell leukemia virus type I and induction of neutralizing antibody by peptide immunization. J Immunol. 1991 Jul 1;147(1):354–360. [PubMed] [Google Scholar]
  23. Taniguchi T., Minami Y. The IL-2/IL-2 receptor system: a current overview. Cell. 1993 Apr 9;73(1):5–8. doi: 10.1016/0092-8674(93)90152-g. [DOI] [PubMed] [Google Scholar]
  24. Vieira J., Messing J. Production of single-stranded plasmid DNA. Methods Enzymol. 1987;153:3–11. doi: 10.1016/0076-6879(87)53044-0. [DOI] [PubMed] [Google Scholar]
  25. Voss S. D., Leary T. P., Sondel P. M., Robb R. J. Identification of a direct interaction between interleukin 2 and the p64 interleukin 2 receptor gamma chain. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2428–2432. doi: 10.1073/pnas.90.6.2428. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES