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

Abstract

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.

• Authors: György Vámosi, Andrea Bodnár, György Vereb, Attila Jenei, Carolyn K Goldman, Jörg Langowski, Katalin Tóth, László Mátyus, János Szöllösi, Thomas A Waldmann, Sándor Damjanovich
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 101 Issue 30 Pg. 11082-7 (Jul 27 2004) ISSN: 0027-8424 [Print] United States
• PMID: 15263076 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• HLA-D Antigens
• Histocompatibility Antigens Class I
• IL15RA protein, human
• Protein Subunits
• Receptors, Interleukin-15
• Receptors, Interleukin-2

Topics

• Antibodies, Monoclonal
• Cell Line, Tumor
• Flow Cytometry
• Fluorescence Resonance Energy Transfer (methods)
• HLA-D Antigens (immunology)
• Histocompatibility Antigens Class I (immunology)
• Humans
• Lymphoma, T-Cell (immunology)
• Membrane Microdomains (immunology)
• Models, Immunological
• Protein Subunits (genetics)
• Receptors, Interleukin-15
• Receptors, Interleukin-2 (genetics)
• Signal Transduction (immunology)
• Spectrometry, Fluorescence
• T-Lymphocytes (immunology)