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

J. Matkó, Andrea Bodnár, G. Vereb, L. Bene, G. Vámosi, Gergely Szentesi, J. Szöllősi, R. Gáspár, Václav Horejsi, Thomas A. Waldmann, S. Damjanovich

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Abstract

Subunits (α, β and γ) 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 β and γ chains are shared by other cytokines (e.g. IL-7, IL-9, IL-15). However, the molecular mechanisms responsible for recruiting/sorting the α 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 immunobiochemical techniques. In addition to the β and γc chains constitutively expressed in detergent-resistant membrane fractions (DRMs) of T cells, IL-2Rα (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-β-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 β and γc 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.

Original languageEnglish
Pages (from-to)1199-1208
Number of pages10
JournalEuropean Journal of Biochemistry
Volume269
Issue number4
DOIs
Publication statusPublished - 2002

Fingerprint

Membrane Microdomains
T-cells
Interleukin-2 Receptors
Lymphoma
Leukemia
Membranes
Cell Line
Interleukin-2
Adult T Cell Leukemia Lymphoma
Interleukin-9
T-Lymphocytes
Interleukin-15
Interleukin-7
Signal transduction
Fluorescence Resonance Energy Transfer
Phosphorylation
Gangliosides
Confocal microscopy
Cyclodextrins
HLA-DR Antigens

Keywords

  • Cell proliferation
  • Cytokine receptors
  • Fluorescence energy transfer
  • Lipid rafts
  • T lymphocytes

ASJC Scopus subject areas

  • Biochemistry

Cite this

GPI-microdomains (membrane rafts) and signaling of the multi-chain interleukin-2 receptor in human lymphoma/leukemia T cell lines. / Matkó, J.; Bodnár, Andrea; Vereb, G.; Bene, L.; Vámosi, G.; Szentesi, Gergely; Szöllősi, J.; Gáspár, R.; Horejsi, Václav; Waldmann, Thomas A.; Damjanovich, S.

In: European Journal of Biochemistry, Vol. 269, No. 4, 2002, p. 1199-1208.

Research output: Contribution to journalArticle

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AU - Bodnár, Andrea

AU - Vereb, G.

AU - Bene, L.

AU - Vámosi, G.

AU - Szentesi, Gergely

AU - Szöllősi, J.

AU - Gáspár, R.

AU - Horejsi, Václav

AU - Waldmann, Thomas A.

AU - Damjanovich, S.

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