A biophysical approach to IL-2 and IL-15 receptor function:: Localization, conformation and interactions

Interleukin-2 and interleukin-15 (IL-2, IL-15) are key participants in T and NK cell activation and function. Sharing the beta and gamma receptor subunits results in several common functions: e.g. the promotion of T cell proliferation. On the other hand, due to their distinct alpha receptor subunits, they also play opposing roles in immune processes such as activation induced cell death and immunological memory. Divergence of signaling pathways must ensue already at the plasma membrane where the cytokines interact with their receptors. Therefore understanding molecular details of receptor organization and mapping interactions with other membrane proteins that might influence receptor conformation and function, are of key importance. Biophysical/advanced microscopic methods (fluorescence resonance energy transfer (FRET), fluorescence crosscorrelation spectroscopy (FCCS), near-field scanning optical microscopy (NSOM), X-ray crystallography, surface plasmon resonance, NMR spectroscopy) have been instrumental in clarifying the details of receptor structure and organization from the atomic level to the assembly and dynamics of supramolecular clusters. In this short review some important contributions shaping our current view of IL-2 and IL-15 receptors are presented. (C) 2008 Elsevier B.V. All rights reserved.