IL-2 and IL-15 receptor alpha-subunits are coexpressed in a supramolecular receptor cluster in lipid rafts of T cells

Sándor Damjanovich (1,2); György Vámosi (2); Andrea Bodnár (2); György Vereb (1); Attila Jenei (1); Jörg Langowski (3); Katalin Tóth (3); Carolyn K. Goldman (4); László Mátyus (1); János Szöllősi (1) and Thomas A. Waldmann (4)

(1) Dept. of Biophysics and Cell Biology and (2) Cell Biophysics Research Group of the Hung. Acad. of Sciences, RCMM, University of Debrecen; (3) Deutsches Krebsforschungszentrum, Heidelberg; (4) Metabolism Branch, NCI, NIH, Bethesda

The private alpha-chains of IL-2 and IL-15 receptors (IL-2R and IL-15R) share the signaling beta- and gamma(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-2Ralpha, IL-15Ralpha, IL-2/15Rbeta and gamma(c)subunits, 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-15Ralpha with IL-2Ralpha and MHC class I. A model was generated for subunit switching between IL-2Ralpha and IL-15Ralpha upon the binding of the appropriate cytokine resulting in the formation of high-affinity heterotrimeric receptors. This model suggests a direct role for the alpha-subunits, to which no definite function has been assigned so far, in tuning cellular responses to IL-2 or IL-15. In addition, both alpha-chains were at least partially homodimerized/oligomerized, which could be the basis of distinct signaling pathways by the two cytokines.

Email: dami@jaguar.dote.hu

Address: Dept. of Biophysics and Cell Biology, University of Debrecen, H-4012 Debrecen, Nagyerdei krt. 98., Hungary