Structure—Function Relations for the Interleukin-2 Receptor
The original study of IL-2 binding to activated lymphocytes (Robb et al., 1981) described a high-affinity receptor—ligand interaction that fit nicely with the extremely low concentrations of IL-2 that were necessary to promote cellular proliferation. Subsequent investigations, however, indicated that the interaction of IL-2 with cells was not so simple. In particular, antibodies to the IL-2 receptor detected far more receptor molecules on the cell surface than high-affinity IL-2 binding sites (Leonard et al.,1982). As IL-2 became more plentiful, the IL-2 binding assays were extended to higher concentrations of ligand, revealing a second class of low-affinity sites (Robb et al.,1984). The latter sites appeared to account for most or all of the discrepancy between the number of receptors detected with antibodies and the original numerical estimates of high-affinity binding sites. The molecular basis for the two affinity classes of receptor, however, remained unclear. Possible explanations included: (1) the high-and low-affinity sites consisted of distinct IL-2 binding molecules; (2) the affinity difference occurred as a result of variable post-translational modifications of a single IL-2-binding molecule; (3) the difference arose from conformational changes in a single receptor protein, perhaps as a result of homodimer formation or association with a second receptor subunit; and (4) the difference was caused by the effect of a second receptor subunit, present in high-affinity binding sites, which partici-pated directly in ligand binding. In the past year, several laboratories have obtained evidence that the last explanation is indeed the basis for the multiple affinities of the IL-2 receptor.
KeywordsDisulfide Structure Natural Killer Precursor
Unable to display preview. Download preview PDF.
- Leonard, W. J., Depper, J. M., Crabtree, G. R., Rudikoff, S., Pumphrey, J., Robb, R. J., Krönke, M., Svetlik, P. B., Peffer, N. J., Waldmann, T. A., and Greene, W. C., 1984, Molecular cloning and expression of cDNAs for the human interleukin-2 receptor, Nature 311:626–631.PubMedCrossRefGoogle Scholar
- Neeper, M. P., Kuo, L.-M., Kiefer, M. C., and Robb, R. J., 1987, Structure—function relationships for the IL 2—receptor system. III. Tac protein missing amino acids 102–173 (exon 4) is unable to bind IL 2. Detection of spliced protein after L cell transfection, J. Immunol. 138:3532–3538.PubMedGoogle Scholar
- Ortaldo, J. R., Mason, A. T., Gerard, J. P., Henderson, L. E., Farrar, W., Hopkins, R. F., Herberman, R. B., and Rabin, H., 1984, Effects of natural and recombinant IL-2 on regulation of IFN,. production and natural killer activity: Lack of involvement of the Tac antigen for these immunoregulatory effects, J. Immunol. 133:779–783.PubMedGoogle Scholar
- Robb, R. J., 1985, Human interleukin 2, in: Methods in Enzymology (G. diSabato, J. J. Langone, and H. VanVunakis, eds.), Vol. 116, pp. 493–525, Academic Press, Orlando, FLGoogle Scholar
- Robb, R. J., and Lin, Y., 1984, T-cell growth factor: Purification, interaction with a cellular receptor, and in vitro synthesis, in: Thymic Hormones and Lymphokines ‘83 (A. L. Goldstein, ed.), pp. 247–256, Plenum Press, New York.Google Scholar
- Rubin, L. A., Kurman, C. C., Fritz, M. E., Biddison, W. E., Boutin, B., Yarchoan, R., and Nelson, D. L., 1985b, Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro, J. Immunol. 135:3172–3177.Google Scholar
- Shackelford, D. A., and Trowbridge, I. S., 1986, Structural features of the human interleukin-2 receptor, in: Advances in Gene Technology: Molecular Biology of the Endocrine System. (D. Puett, F. Ahmed, S. Black, D. M. Lopez, H. H. Melner, W. A. Scott, and W. J. Whelan, eds.), pp. 390–391, Cambridge University Press, Cambridge, England.Google Scholar
- Yodoi, J., Teshigawara, K., Nikaido, T., Fukui, K., Noma, T., Honjo, T., Takigawa, M., Sasaki, M., Minato, N., Tsudo, M., Uchiyama, T., and Maeda, M., 1985, 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.PubMedGoogle Scholar