No abstract

The private ␣-chains of IL-2 and IL-15 receptors (IL-2R and IL-15R) share the signaling ␤-and ␥c-subunits, resulting in both common and contrasting roles of IL-2 and IL-15 in T cell function. Knowledge of the cytokine-dependent subunit assembly is indispensable for understanding the paradox of distinct signaling capacities. By using fluorescence resonance energy transfer and confocal microscopy, we have shown that IL-2R␣, IL-15R␣, IL-2͞15R␤ and ␥ csubunits, as well as MHC class I and II glycoproteins formed supramolecular receptor clusters in lipid rafts of the T lymphoma line Kit 225 FT7.10. Fluorescence crosscorrelation microscopy demonstrated the comobility of IL-15R␣ with IL-2R␣ and MHC class I. A model was generated for subunit switching between IL-2R␣ and IL-15R␣ upon the binding of the appropriate cytokine resulting in the formation of high-affinity heterotrimeric receptors. This model suggests a direct role for the ␣-subunits, to which no definite function has been assigned so far, in tuning cellular responses to IL-2 or IL-15. In addition, both ␣-chains were at least partially homodimerized͞oligomerized, which could be the basis of distinct signaling pathways by the two cytokines.