Solution assembly of the pseudo-high affinity and intermediate affinity interleukin-2 receptor complexes

The high affinity interleukin-2 receptor is composed of three cell surface subunits, IL-2R alpha, IL-2R beta, and IL-2R gamma. Functional forms of the IL-2 receptor exist, however, that enlist only two of the three subunits. On activated T-cells, the alpha- and beta-subunits combine as a preformed h eterodimer (the pseudo-high affinity receptor) that serves to capture IL-2. On a subpopulation of natural killer cells, the beta- and gamma-subunits i nteract in a ligand-dependent manner to form the intermediate affinity rece ptor site. Previously, we have demonstrated the feasibility of employing co iled-coil molecular recognition for the solution assembly of a heteromeric IL-2 receptor complex. In that study, although the receptor was functional, the coiled-coil complex was a trimer rather than the desired heterodimer. We have now redesigned the hydrophobic heptad sequences of the coiled-coils to generate soluble forms of both the pseudo-high affinity and the interme diate affinity heterodimeric IL-2 receptors. The properties of these comple xes were examined and their relevance to the physiological IL-2 receptor me chanism is discussed.