Evidence for p55-p75 heterodimers in the absence of IL-2 from Scatchard plot analysis.
The high affinity receptor for 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 proposes that the high affinity receptor is formed via stepwise binding 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 performed heterodimer model the p55 and p75 chains form a non-covalently linked high affinity heterodimer in the absence of IL-2. We show that these two models can be distinguished on the basis of equilibrium binding experiments using cell lines expressing different numbers of p55 chains. To make this distinction we develop a general model for the interaction of IL-2 with its various receptors. We than analyze the case in which heterodimers exist in the absence of IL-2 and the case in which no preformed heterodimers exist. For both cases we predict the shape of equilibrium Scatchard plots. We then 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. The models that we develop should have general applicability to the entire class of receptor systems in which low and intermediate affinity chains interact to constitute a high affinity receptor.
Goldstein
B
B
Theoretical Division, Los Alamos National Laboratory, NM 87545.
Jones
D
D
Kevrekidis
I G
IG
Perelson
A S
AS
D002462:Cell Membrane / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D007700:Kinetics; D008954:Models, Biological; D008970:Molecular Weight; D011487:Protein Conformation; D015375:Receptors, Interleukin-2 / Q000737:chemistry* / Q000378:metabolism
D007376:Interleukin-2; D015375:Receptors, Interleukin-2