MHC I Expression Regulates Co-clustering and Mobility of Interleukin-2 and -15 Receptors in T Cells.

Autor:	Mocsár G; Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary., Volkó J; Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary., Rönnlund D; Department of Applied Physics/Experimental Biomolecular Physics, Royal Institute of Technology, Albanova University Center, Stockholm, Sweden., Widengren J; Department of Applied Physics/Experimental Biomolecular Physics, Royal Institute of Technology, Albanova University Center, Stockholm, Sweden., Nagy P; Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary., Szöllősi J; Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; Cell Biology and Signaling Research Group of the Hungarian Academy of Sciences and the University of Debrecen, Debrecen, Hungary., Tóth K; German Cancer Research Center, Biophysics of Macromolecules, Heidelberg, Germany., Goldman CK; Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Damjanovich S; Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary., Waldmann TA; Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Bodnár A; Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary., Vámosi G; Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. Electronic address: vamosig@med.unideb.hu.
Jazyk:	angličtina
Zdroj:	Biophysical journal [Biophys J] 2016 Jul 12; Vol. 111 (1), pp. 100-12.
DOI:	10.1016/j.bpj.2016.05.044
Abstrakt:	MHC glycoproteins form supramolecular clusters with interleukin-2 and -15 receptors in lipid rafts of T cells. The role of highly expressed MHC I in maintaining these clusters is unknown. We knocked down MHC I in FT7.10 human T cells, and studied protein clustering at two hierarchic levels: molecular aggregations and mobility by Förster resonance energy transfer and fluorescence correlation spectroscopy; and segregation into larger domains or superclusters by superresolution stimulated emission depletion microscopy. Fluorescence correlation spectroscopy-based molecular brightness analysis revealed that the studied molecules diffused as tight aggregates of several proteins of a kind. Knockdown reduced the number of MHC I containing molecular aggregates and their average MHC I content, and decreased the heteroassociation of MHC I with IL-2Rα/IL-15Rα. The mobility of not only MHC I but also that of IL-2Rα/IL-15Rα increased, corroborating the general size decrease of tight aggregates. A multifaceted analysis of stimulated emission depletion images revealed that the diameter of MHC I superclusters diminished from 400-600 to 200-300 nm, whereas those of IL-2Rα/IL-15Rα hardly changed. MHC I and IL-2Rα/IL-15Rα colocalized with GM1 ganglioside-rich lipid rafts, but MHC I clusters retracted to smaller subsets of GM1- and IL-2Rα/IL-15Rα-rich areas upon knockdown. Our results prove that changes in expression level may significantly alter the organization and mobility of interacting membrane proteins. (Copyright © 2016 Biophysical Society. All rights reserved.)
Databáze:	MEDLINE
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