IL-2 and IL-15 receptor alpha-subunits are coexpressed in a supramolecular receptor cluster in lipid rafts of T cells.
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-2R alpha, IL-15R alpha, IL-2/15R beta 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-15R alpha with IL-2R alpha and MHC class I. A model was generated for subunit switching between IL-2R alpha and IL-15R alpha 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.
Vámosi
György
G
Cell Biophysics Research Group of the Hungarian Academy of Sciences, Debrecen, Hungary.
Bodnár
Andrea
A
Vereb
György
G
Jenei
Attila
A
Goldman
Carolyn K
CK
Langowski
Jörg
J
Tóth
Katalin
K
Mátyus
László
L
Szöllösi
János
J
Waldmann
Thomas A
TA
Damjanovich
Sándor
S
D000911:Antibodies, Monoclonal; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods; D006681:HLA-D Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D016399:Lymphoma, T-Cell / Q000276:immunology; D021962:Membrane Microdomains / Q000276:immunology*; D018448:Models, Immunological; D021122:Protein Subunits / Q000235:genetics*; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000235:genetics*; D015398:Signal Transduction / Q000276:immunology; D013050:Spectrometry, Fluorescence; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D006681:HLA-D Antigens; D015395:Histocompatibility Antigens Class I; C508024:IL15RA protein, human; D021122:Protein Subunits; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2