THE ROLE OF LOW-AFFINITY INTERLEUKIN-2 RECEPTORS IN AUTOCRINE LIGAND-BINDING - ALTERNATIVE MECHANISMS FOR ENHANCED BINDING EFFECT

T-cell proliferation is regulated by the autocrine ligand interleukin- 2 (IL-2), for which these cells possess dual, low-affinity and high-af finity receptor populations. Proliferation stimulated by IL-2 is depen dent upon ligand binding to p75, a component of the high-affinity rece ptor. As with other cells exhibiting dual receptor systems, a central question is, therefore: what is the role of the low-affinity receptor population? We apply a mathematical modeling approach to examine three alternative mechanisms that have been suggested for the role of low-a ffinity receptors: a ligand reservoir, a receptor reservoir, and a lig and carrier. Using model parameter values specific to the IL-2/T-cell system, we find that only the ligand carrier mechanism leads to bindin g of autocrine ligand to high-affinity receptors that is increased ove r levels found on a single, pre-formed high-affinity receptor populati on. With the ligand reservoir and the receptor reservoir mechanisms, t he presence of the low-affinity receptors actually diminishes high-aff inity receptor binding due to competition. In contrast, excess low-aff nity receptors can act to enhance the level of high-affinity receptor complexes when membrane transport is included, indicating that should this mechanism be inhibited, cell response could potentially be reduce d or eliminated. The ligand carrier effect is especially significant f or cells expressing a large number (>10(5) receptors/cell) low-affinit y receptors, and at low cell densities (<10(4) cells/ml). This may at least partially account for the behavior demonstrated by early phase a dult T-cell leukemia cells.