GPI-microdomains (membrane rafts) and signaling of the multi-chain interleukin-2 receptor in human lymphoma/leukemia T cell lines

Eur J Biochem. 2002 Feb;269(4):1199-208. doi: 10.1046/j.0014-2956.2002.02759.x.


Subunits (alpha, beta and gamma) of the interleukin-2 receptor complex (IL-2R) are involved in both proliferative and activation-induced cell death (AICD) signaling of T cells. In addition, the signaling beta and gamma chains are shared by other cytokines (e.g. IL-7, IL-9, IL-15). However, the molecular mechanisms responsible for recruiting/sorting the alpha chains to the signaling chains at the cell surface are not clear. Here we show, in four cell lines of human adult T cell lymphoma/leukemia origin, that the three IL-2R subunits are compartmented together with HLA glycoproteins and CD48 molecules in the plasma membrane, by means of fluorescence resonance energy transfer (FRET), confocal microscopy and immuno-biochemical techniques. In addition to the beta and gamma(c) chains constitutively expressed in detergent-resistant membrane fractions (DRMs) of T cells, IL-2Ralpha (CD25) was also found in DRMs, independently of its ligand-occupation. Association of CD25 with rafts was also confirmed by its colocalization with GM-1 ganglioside. Depletion of membrane cholesterol using methyl-beta-cyclodextrin substantially reduced co-clustering of CD25 with CD48 and HLA-DR, as well as the IL-2 stimulated tyrosine-phosphorylation of STATs (signal transducer and activator of transcription). These data indicate a GPI-microdomain (raft)-assisted recruitment of CD25 to the vicinity of the signaling beta and gamma(c) chains. Rafts may promote rapid formation of a high affinity IL-2R complex, even at low levels of IL-2 stimulus, and may also form a platform for the regulation of IL-2 induced signals by GPI-proteins (e.g. CD48). Based on these data, the integrity of these GPI-microdomains seems critical in signal transduction through the IL-2R complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / isolation & purification
  • CD48 Antigen
  • G(M1) Ganglioside / isolation & purification
  • Glycoproteins / isolation & purification
  • HLA Antigens / isolation & purification
  • Humans
  • Interleukin-2 Receptor alpha Subunit
  • Leukemia, T-Cell / metabolism*
  • Lymphoma, T-Cell / metabolism*
  • Membrane Microdomains*
  • Receptors, Interleukin / isolation & purification
  • Receptors, Interleukin-2 / isolation & purification*
  • Signal Transduction
  • Tumor Cells, Cultured


  • Antigens, CD
  • CD48 Antigen
  • CD48 protein, human
  • Glycoproteins
  • HLA Antigens
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • Receptors, Interleukin
  • Receptors, Interleukin-2
  • G(M1) Ganglioside