Interaction of Interleukin-2 with its Cell Surface Receptors: Interpretation of Equilibrium Binding Experiments via Scatchard Plots
The high affinity receptor for interleukin 2 (IL-2) is composed of at least two chains, a p55 chain that binds IL-2 with low affinity and a p75 chain that binds with intermediate affinity. Two molecular mechanisms have been proposed for the formation of the high affinity receptor-ligand complex. The affinity conversion model proposed by Honjo and coworkers (Saito et al., 1988) suggests that the high affinity receptor is formed via stepwise binding reactions in which IL-2 first binds to the p55 chain and the resulting complex then associates with the p75 chain to form a high affinity ternary complex. In the preformed heterodimer model the p55 and p75 chains form a non-covalently linked high affinity heterodimer in the absence of IL-2. We analyze these models theoretically and show that they can be distinguished on the basis of equilibrium binding experiments using cell lines expressing different numbers of p55 chains. We show that published IL-2 binding studies are consistent with a model in which a large concentration of preformed heterodimers is present on the cell surface and inconsistent with a model in which preformed heterodimers are absent from the cell surface.
KeywordsPolypeptide Librium Kato Phorbol eDNA
Unable to display preview. Download preview PDF.
- Hayashida, K., Kitamura, T., Gorman, D. M., Arai, K., Yokota, T., and Miyajima, A. (1990). Molecular cloning of the second subunit of the receptor for human granulocytemacrophage colony-stimulating factor (GM-CSF): Reconstitution of a high affinity GM-CSF receptor. Proc. Natl. Acad. Set. USA 87, 9655–9659.CrossRefGoogle Scholar
- Hill, T. L. (1977). Free Energy Transduction in Biology. The Steady-State Kinetic and Thermodynamic Formalism. Academic Press, New York. p. 4.Google Scholar
- Jones, D. A., Kevrekidis, I. G., Perelson, A. S. and Goldstein, B. G. (1989). A model of IL-2 binding and receptor-mediated internalization. Paper No. 17e. Extended Abstracts and Papers, Am. Inst. Chem. Eng. 1989 Annual Meeting, San Francisco, CA.Google Scholar
- Takaki, S., Mita, S., Kitamura, T., Yonehara, S., Yamaguchi, N., Tominaga, A., Miyajima, A., and Takatsu, K. (1991). Identification of the second subunit of the murine interleukin-5 receptor: Interleukin-3 receptor-like protein, AIC2B is a component of the high affinity interleukin-5 receptor. EMBO J. 10, 2833–2838.PubMedGoogle Scholar
- Tavernier, J., Devos, R., Cornelis, S., Tuypens, T., Van der Heyden, J., Fiers, W., and Plaetinck, G. (1991). A human high affinity interleukin-5 receptor (IL5R) is composed of an IL5-specific a chain and a ¡3 chain shared with the receptor for GM-CSF. Cell 66, 1175–1184.PubMedCrossRefGoogle Scholar