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Cell Surface Organization of Stress-inducible Proteins ULBP and MICA That Stimulate Human NK Cells and T Cells via NKG2D

Cell surface proteins major histocompatibility complex (MHC) class I–related chain A (MICA) and UL16-binding proteins (ULBP) 1, 2, and 3 are up-regulated upon infection or tumor transformation and can activate human natural killer (NK) cells. Patches of cross-linked raft resident ganglioside GM1 col...

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Autores principales: Eleme, Konstantina, Taner, Sabrina B., Önfelt, Björn, Collinson, Lucy M., McCann, Fiona E., Chalupny, N. Jan, Cosman, David, Hopkins, Colin, Magee, Anthony I., Davis, Daniel M.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211882/
https://www.ncbi.nlm.nih.gov/pubmed/15051759
http://dx.doi.org/10.1084/jem.20032194
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author Eleme, Konstantina
Taner, Sabrina B.
Önfelt, Björn
Collinson, Lucy M.
McCann, Fiona E.
Chalupny, N. Jan
Cosman, David
Hopkins, Colin
Magee, Anthony I.
Davis, Daniel M.
author_facet Eleme, Konstantina
Taner, Sabrina B.
Önfelt, Björn
Collinson, Lucy M.
McCann, Fiona E.
Chalupny, N. Jan
Cosman, David
Hopkins, Colin
Magee, Anthony I.
Davis, Daniel M.
author_sort Eleme, Konstantina
collection PubMed
description Cell surface proteins major histocompatibility complex (MHC) class I–related chain A (MICA) and UL16-binding proteins (ULBP) 1, 2, and 3 are up-regulated upon infection or tumor transformation and can activate human natural killer (NK) cells. Patches of cross-linked raft resident ganglioside GM1 colocalized with ULBP1, 2, 3, or MICA, but not CD45. Thus, ULBPs and MICA are expressed in lipid rafts at the cell surface. Western blotting revealed that glycosylphosphatidylinositol (GPI)-anchored ULBP3 but not transmembrane MICA, MHC class I protein, or transferrin receptor, accumulated in detergent-resistant membranes containing GM1. Thus, MICA may have a weaker association with lipid rafts than ULBP3, yet both proteins accumulate at an activating human NK cell immune synapse. Target cell lipid rafts marked by green fluorescent protein–tagged GPI also accumulate with ULBP3 at some synapses. Electron microscopy reveals constitutive clusters of ULBP at the cell surface. Regarding a specific molecular basis for the organization of these proteins, ULBP1, 2, and 3 and MICA are lipid modified. ULBP1, 2, and 3 are GPI anchored, and we demonstrate here that MICA is S-acylated. Finally, expression of a truncated form of MICA that lacks the putative site for S-acylation and the cytoplasmic tail can be expressed at the cell surface, but is unable to activate NK cells.
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spelling pubmed-22118822008-03-11 Cell Surface Organization of Stress-inducible Proteins ULBP and MICA That Stimulate Human NK Cells and T Cells via NKG2D Eleme, Konstantina Taner, Sabrina B. Önfelt, Björn Collinson, Lucy M. McCann, Fiona E. Chalupny, N. Jan Cosman, David Hopkins, Colin Magee, Anthony I. Davis, Daniel M. J Exp Med Brief Definitive Report Cell surface proteins major histocompatibility complex (MHC) class I–related chain A (MICA) and UL16-binding proteins (ULBP) 1, 2, and 3 are up-regulated upon infection or tumor transformation and can activate human natural killer (NK) cells. Patches of cross-linked raft resident ganglioside GM1 colocalized with ULBP1, 2, 3, or MICA, but not CD45. Thus, ULBPs and MICA are expressed in lipid rafts at the cell surface. Western blotting revealed that glycosylphosphatidylinositol (GPI)-anchored ULBP3 but not transmembrane MICA, MHC class I protein, or transferrin receptor, accumulated in detergent-resistant membranes containing GM1. Thus, MICA may have a weaker association with lipid rafts than ULBP3, yet both proteins accumulate at an activating human NK cell immune synapse. Target cell lipid rafts marked by green fluorescent protein–tagged GPI also accumulate with ULBP3 at some synapses. Electron microscopy reveals constitutive clusters of ULBP at the cell surface. Regarding a specific molecular basis for the organization of these proteins, ULBP1, 2, and 3 and MICA are lipid modified. ULBP1, 2, and 3 are GPI anchored, and we demonstrate here that MICA is S-acylated. Finally, expression of a truncated form of MICA that lacks the putative site for S-acylation and the cytoplasmic tail can be expressed at the cell surface, but is unable to activate NK cells. The Rockefeller University Press 2004-04-05 /pmc/articles/PMC2211882/ /pubmed/15051759 http://dx.doi.org/10.1084/jem.20032194 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Brief Definitive Report
Eleme, Konstantina
Taner, Sabrina B.
Önfelt, Björn
Collinson, Lucy M.
McCann, Fiona E.
Chalupny, N. Jan
Cosman, David
Hopkins, Colin
Magee, Anthony I.
Davis, Daniel M.
Cell Surface Organization of Stress-inducible Proteins ULBP and MICA That Stimulate Human NK Cells and T Cells via NKG2D
title Cell Surface Organization of Stress-inducible Proteins ULBP and MICA That Stimulate Human NK Cells and T Cells via NKG2D
title_full Cell Surface Organization of Stress-inducible Proteins ULBP and MICA That Stimulate Human NK Cells and T Cells via NKG2D
title_fullStr Cell Surface Organization of Stress-inducible Proteins ULBP and MICA That Stimulate Human NK Cells and T Cells via NKG2D
title_full_unstemmed Cell Surface Organization of Stress-inducible Proteins ULBP and MICA That Stimulate Human NK Cells and T Cells via NKG2D
title_short Cell Surface Organization of Stress-inducible Proteins ULBP and MICA That Stimulate Human NK Cells and T Cells via NKG2D
title_sort cell surface organization of stress-inducible proteins ulbp and mica that stimulate human nk cells and t cells via nkg2d
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211882/
https://www.ncbi.nlm.nih.gov/pubmed/15051759
http://dx.doi.org/10.1084/jem.20032194
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