Uptake of CCR7 by KIR2DS4+ NK Cells Is Induced upon Recognition of Certain HLA-C Alleles

The KIR2DS4 receptor is the oldest KIR2DS expressed by human NK lymphocytes. The specificity of recognition of this receptor for various HLA class I alleles has been demonstrated; however it remains poorly understood whether these interactions may result in the activation of some specific functions...

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Main Authors: Silvia Pesce, Simona Carlomagno, Alessandro Moretta, Simona Sivori, Emanuela Marcenaro
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2015/754373
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author Silvia Pesce
Simona Carlomagno
Alessandro Moretta
Simona Sivori
Emanuela Marcenaro
author_facet Silvia Pesce
Simona Carlomagno
Alessandro Moretta
Simona Sivori
Emanuela Marcenaro
author_sort Silvia Pesce
collection DOAJ
description The KIR2DS4 receptor is the oldest KIR2DS expressed by human NK lymphocytes. The specificity of recognition of this receptor for various HLA class I alleles has been demonstrated; however it remains poorly understood whether these interactions may result in the activation of some specific functions in NK cells. Here, we examined the functional outcome of the KIR2DS4/HLA class I interaction by the use of an alternative functional system based on the ability of KIR2DS4 to regulate the mechanism of trogocytosis by NK cells. We demonstrate that KIR2DS4 can induce the uptake of CCR7 by KIR2DS4+ NKG2A+ NK cell clones after interacting with CCR7+ target cells expressing HLA-Cw4 and HLA-Cw6 alleles. However this interaction is not always sufficient to override the inhibition generated by NKG2A expressed on the same NK cells. The recognition of HLA-Cw4 was confirmed by experiments of cytotoxicity against HLA-C-transfected cells. We also show that, different from resting NK cells, the acquisition of CCR7 in response to IL-18 cannot occur in IL2-activated NK cells because of a marked downregulation in their IL-18Rα expression. As a consequence trogocytosis represents the major mechanism by which KIR2DS4+ activated NK cells acquire the expression of this chemokine receptor.
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issn 2314-8861
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language English
publishDate 2015-01-01
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series Journal of Immunology Research
spelling doaj-art-85116759a6814d5082ee86c4c469a6342025-02-03T00:59:54ZengWileyJournal of Immunology Research2314-88612314-71562015-01-01201510.1155/2015/754373754373Uptake of CCR7 by KIR2DS4+ NK Cells Is Induced upon Recognition of Certain HLA-C AllelesSilvia Pesce0Simona Carlomagno1Alessandro Moretta2Simona Sivori3Emanuela Marcenaro4Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, Sezione di Istologia, Via G.B. Marsano 10, 16132 Genova, ItalyDipartimento di Medicina Sperimentale, Università degli Studi di Genova, Sezione di Istologia, Via G.B. Marsano 10, 16132 Genova, ItalyDipartimento di Medicina Sperimentale, Università degli Studi di Genova, Sezione di Istologia, Via G.B. Marsano 10, 16132 Genova, ItalyDipartimento di Medicina Sperimentale, Università degli Studi di Genova, Sezione di Istologia, Via G.B. Marsano 10, 16132 Genova, ItalyDipartimento di Medicina Sperimentale, Università degli Studi di Genova, Sezione di Istologia, Via G.B. Marsano 10, 16132 Genova, ItalyThe KIR2DS4 receptor is the oldest KIR2DS expressed by human NK lymphocytes. The specificity of recognition of this receptor for various HLA class I alleles has been demonstrated; however it remains poorly understood whether these interactions may result in the activation of some specific functions in NK cells. Here, we examined the functional outcome of the KIR2DS4/HLA class I interaction by the use of an alternative functional system based on the ability of KIR2DS4 to regulate the mechanism of trogocytosis by NK cells. We demonstrate that KIR2DS4 can induce the uptake of CCR7 by KIR2DS4+ NKG2A+ NK cell clones after interacting with CCR7+ target cells expressing HLA-Cw4 and HLA-Cw6 alleles. However this interaction is not always sufficient to override the inhibition generated by NKG2A expressed on the same NK cells. The recognition of HLA-Cw4 was confirmed by experiments of cytotoxicity against HLA-C-transfected cells. We also show that, different from resting NK cells, the acquisition of CCR7 in response to IL-18 cannot occur in IL2-activated NK cells because of a marked downregulation in their IL-18Rα expression. As a consequence trogocytosis represents the major mechanism by which KIR2DS4+ activated NK cells acquire the expression of this chemokine receptor.http://dx.doi.org/10.1155/2015/754373
spellingShingle Silvia Pesce
Simona Carlomagno
Alessandro Moretta
Simona Sivori
Emanuela Marcenaro
Uptake of CCR7 by KIR2DS4+ NK Cells Is Induced upon Recognition of Certain HLA-C Alleles
Journal of Immunology Research
title Uptake of CCR7 by KIR2DS4+ NK Cells Is Induced upon Recognition of Certain HLA-C Alleles
title_full Uptake of CCR7 by KIR2DS4+ NK Cells Is Induced upon Recognition of Certain HLA-C Alleles
title_fullStr Uptake of CCR7 by KIR2DS4+ NK Cells Is Induced upon Recognition of Certain HLA-C Alleles
title_full_unstemmed Uptake of CCR7 by KIR2DS4+ NK Cells Is Induced upon Recognition of Certain HLA-C Alleles
title_short Uptake of CCR7 by KIR2DS4+ NK Cells Is Induced upon Recognition of Certain HLA-C Alleles
title_sort uptake of ccr7 by kir2ds4 nk cells is induced upon recognition of certain hla c alleles
url http://dx.doi.org/10.1155/2015/754373
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AT alessandromoretta uptakeofccr7bykir2ds4nkcellsisinduceduponrecognitionofcertainhlacalleles
AT simonasivori uptakeofccr7bykir2ds4nkcellsisinduceduponrecognitionofcertainhlacalleles
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