Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1987 Apr;84(7):2002–2006. doi: 10.1073/pnas.84.7.2002

Interleukin 2 binding molecule distinct from the Tac protein: analysis of its role in formation of high-affinity receptors.

R J Robb, C M Rusk, J Yodoi, W C Greene
PMCID: PMC304571  PMID: 3031660

Abstract

Interleukin 2 (IL-2) receptors on activated T cells exist in high- and low-affinity configurations, both of which share a ligand-binding component known as the Tac protein. Although almost all binding of IL-2 to such cells was inhibited by an antibody to Tac, the predominant component of binding on the natural killer (NK)-like cell line YT was resistant to this reagent. The ligand-binding component on YT cells also differed from Tac in its affinity constant (Kd approximately 8.2 X 10(-10) M vs. Kd approximately equal to 1.1 X 10(-8) M for low-affinity Tac sites) and in its susceptibility to inhibition by certain antibodies to IL-2. When the YT cells were stimulated in a manner that induced expression of the Tac protein, the IL-2 binding sites were converted to a high-affinity configuration (Kd approximately 1.8 X 10(-11) M). Thus, the original binding component on unstimulated YT cells appeared to combine with Tac and IL-2 to produce a high-affinity receptor complex. Use of bifunctional crosslinking agents following ligand binding to unstimulated YT cells yielded covalent IL-2-receptor complexes of 83 and 90 kDa. These complexes were similar in size to those derived from high-affinity receptors on activated T cells and shared a similar fragmentation pattern upon proteolysis. These results demonstrate the existence of a second IL-2 binding component in addition to the Tac protein and suggest that this component combines with Tac and IL-2 to form high-affinity receptor sites.

Full text

PDF
2002

Images in this article

2004Image
on p.2004
2004Image
on p.2004
2004Image
on p.2004

Selected References

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

  1. Ashwell J. D., Robb R. J., Malek T. R. Proliferation of T lymphocytes in response to interleukin 2 varies with their state of activation. J Immunol. 1986 Oct 15;137(8):2572–2578. [PubMed] [Google Scholar]
  2. Bost K. L., Smith E. M., Blalock J. E. Regions of complementarity between the messenger RNAs for epidermal growth factor, transferrin, interleukin-2 and their respective receptors. Biochem Biophys Res Commun. 1985 May 16;128(3):1373–1380. doi: 10.1016/0006-291x(85)91092-7. [DOI] [PubMed] [Google Scholar]
  3. Fujii M., Sugamura K., Sano K., Nakai M., Sugita K., Hinuma Y. High-affinity receptor-mediated internalization and degradation of interleukin 2 in human T cells. J Exp Med. 1986 Mar 1;163(3):550–562. doi: 10.1084/jem.163.3.550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. Kuo L. M., Robb R. J. Structure-function relationships for the IL 2-receptor system. I. Localization of a receptor binding site on IL 2. J Immunol. 1986 Sep 1;137(5):1538–1543. [PubMed] [Google Scholar]
  7. Kuo L. M., Rusk C. M., Robb R. J. Structure-function relationships for the IL 2-receptor system. II. Localization of an IL 2 binding site on high and low affinity receptors. J Immunol. 1986 Sep 1;137(5):1544–1551. [PubMed] [Google Scholar]
  8. Leonard W. J., Depper J. M., Uchiyama T., Smith K. A., Waldmann T. A., Greene W. C. A monoclonal antibody that appears to recognize the receptor for human T-cell growth factor; partial characterization of the receptor. Nature. 1982 Nov 18;300(5889):267–269. doi: 10.1038/300267a0. [DOI] [PubMed] [Google Scholar]
  9. Liang S. M., Thatcher D. R., Liang C. M., Allet B. Studies of structure-activity relationships of human interleukin-2. J Biol Chem. 1986 Jan 5;261(1):334–337. [PubMed] [Google Scholar]
  10. Ortaldo J. R., Mason A. T., Gerard J. P., Henderson L. E., Farrar W., Hopkins R. F., 3rd, Herberman R. B., Rabin H. Effects of natural and recombinant IL 2 on regulation of IFN gamma production and natural killer activity: lack of involvement of the Tac antigen for these immunoregulatory effects. J Immunol. 1984 Aug;133(2):779–783. [PubMed] [Google Scholar]
  11. Ralph P., Jeong G., Welte K., Mertelsmann R., Rabin H., Henderson L. E., Souza L. M., Boone T. C., Robb R. J. Stimulation of immunoglobulin secretion in human B lymphocytes as a direct effect of high concentrations of IL 2. J Immunol. 1984 Nov;133(5):2442–2445. [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. Robb R. J., Kutny R. M., Panico M., Morris H., DeGrado W. F., Chowdhry V. Posttranslational modification of human T-cell growth factor. Biochem Biophys Res Commun. 1983 Nov 15;116(3):1049–1055. doi: 10.1016/s0006-291x(83)80248-4. [DOI] [PubMed] [Google Scholar]
  15. Rubin L. A., Kurman C. C., Biddison W. E., Goldman N. D., Nelson D. L. A monoclonal antibody 7G7/B6, binds to an epitope on the human interleukin-2 (IL-2) receptor that is distinct from that recognized by IL-2 or anti-Tac. Hybridoma. 1985 Summer;4(2):91–102. doi: 10.1089/hyb.1985.4.91. [DOI] [PubMed] [Google Scholar]
  16. Sharon M., Klausner R. D., Cullen B. R., Chizzonite R., Leonard W. J. Novel interleukin-2 receptor subunit detected by cross-linking under high-affinity conditions. Science. 1986 Nov 14;234(4778):859–863. doi: 10.1126/science.3095922. [DOI] [PubMed] [Google Scholar]
  17. Shirakawa F., Tanaka Y., Eto S., Suzuki H., Yodoi J., Yamashita U. Effect of interleukin 1 on the expression of interleukin 2 receptor (Tac antigen) on human natural killer cells and natural killer-like cell line (YT cells). J Immunol. 1986 Jul 15;137(2):551–556. [PubMed] [Google Scholar]
  18. Teshigawara K., Wang H. M., Kato K., Smith K. A. Interleukin 2 high-affinity receptor expression requires two distinct binding proteins. J Exp Med. 1987 Jan 1;165(1):223–238. doi: 10.1084/jem.165.1.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Tsudo M., Kozak R. W., Goldman C. K., Waldmann T. A. Demonstration of a non-Tac peptide that binds interleukin 2: a potential participant in a multichain interleukin 2 receptor complex. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9694–9698. doi: 10.1073/pnas.83.24.9694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Yodoi J., Teshigawara K., Nikaido T., Fukui K., Noma T., Honjo T., Takigawa M., Sasaki M., Minato N., Tsudo M. 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. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES