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First published online February 20, 2008
doi: 10.1242/10.1242/jcs.019513

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Nanometer-scale organization of the alpha subunits of the receptors for IL2 and IL15 in human T lymphoma cells

¹ Applied Optics group, Faculty of Science and Technology, MESA+ Research Institute for Nanotechnology, University of Twente, PO Box 217, 7500 AE Enschede, The Netherlands
² Cell Biology and Signaling Research Group of the Hungarian Academy of Sciences, Research Center for Molecular Medicine, Medical and Health Science Center, University of Debrecen, PO Box 39, 4032 Debrecen, Hungary
³ Department of Biophysics and Cell Biology, Research Center for Molecular Medicine, Medical and Health Science Center, University of Debrecen, PO Box 39, 4012 Debrecen, Hungary
⁴ Metabolism Branch/National Cancer Institute, National Institutes of Health, Bethesda MD 20892-1374, USA
⁵ ICFO-Institut de Ciències Fotòniques, 08860 Barcelona, Spain
⁶ ICREA-Institució Catalana de Recerca i Estudis Avançats, 08010 Barcelona, Spain
⁷ IBEC-Institut de Bioenginyeria de Catalunya and CIBER-BNN, Josep Samitier 1-5, Barcelona 08028, Spain

^* Authors for correspondence (e-mail: jenei{at}jaguar.dote.hu; mgarcia{at}pcb.ub.es)

Accepted 28 November 2007

Interleukin 2 and interleukin 15 (IL2 and IL15, respectively) provide quite distinct contributions to T-cell-mediated immunity, despite having similar receptor composition and signaling machinery. As most of the proposed mechanisms underlying this apparent paradox attribute key significance to the individual -chains of IL2 and IL15 receptors, we investigated the spatial organization of the receptors IL2R and IL15R at the nanometer scale expressed on a human CD4⁺ leukemia T cell line using single-molecule-sensitive near-field scanning optical microscopy (NSOM). In agreement with previous findings, we here confirm clustering of IL2R and IL15R at the submicron scale. In addition to clustering, our single-molecule data reveal that a non-negligible percentage of the receptors are organized as monomers. Only a minor fraction of IL2R molecules reside outside the clustered domains, whereas 30% of IL15R molecules organize as monomers or small clusters, excluded from the main domain regions. Interestingly, we also found that the packing densities per unit area of both IL2R and IL15R domains remained constant, suggesting a `building block' type of assembly involving repeated structures and composition. Finally, dual-color NSOM demonstrated co-clustering of the two -chains. Our results should aid understanding the action of the IL2R-IL15R system in T cell function and also might contribute to the more rationale design of IL2R- or IL15R-targeted immunotherapy agents for treating human leukemia.

Key words: Near-field scanning optical microscopy (NSOM), Interleukin receptors IL2R, IL15R, Single-molecule detection, nanometer-scale membrane organization