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MHC I Expression Regulates Co-clustering and Mobility of Interleukin-2 and-15 Receptors in T Cells
KTH, School of Engineering Sciences (SCI), Applied Physics, Experimental Biomolecular Physics.
KTH, School of Engineering Sciences (SCI), Applied Physics, Experimental Biomolecular Physics.
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2016 (English)In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 111, no 1, 100-112 p.Article in journal (Refereed) Published
Abstract [en]

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 Forster 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-2R alpha/IL-15R alpha. The mobility of not only MHC I but also that of IL-2R alpha/IL-15R alpha 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-2R alpha/IL-15R alpha hardly changed. MHC I and IL-2R alpha/IL-15R alpha colocalized with GM1 ganglioside-rich lipid rafts, but MHC I clusters retracted to smaller subsets of GM1-and IL-2R alpha/IL-15R alpha-rich areas upon knockdown. Our results prove that changes in expression level may significantly alter the organization and mobility of interacting membrane proteins.

Place, publisher, year, edition, pages
Cell Press , 2016. Vol. 111, no 1, 100-112 p.
Keyword [en]
Resonance Energy-Transfer, Hla Class-I, Fluorescence Correlation Spectroscopy, Human Lymphoblastoid-Cells, Plasma-Membrane, Monoclonal-Antibody, Il-2 Receptor, Insulin-Receptors, Lymphoma-Cells, Lipid Rafts
National Category
Biophysics
Identifiers
URN: urn:nbn:se:kth:diva-192411DOI: 10.1016/j.bpj.2016.05.044ISI: 000380371400013PubMedID: 27410738OAI: oai:DiVA.org:kth-192411DiVA: diva2:968752
Note

QC 20160912

Available from: 2016-09-12 Created: 2016-09-12 Last updated: 2016-09-12Bibliographically approved

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Rönnlund, DanielWidengren, Jerker
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