INHIBITION OF THE NKG2D ACTIVATING RECEPTOR EXPRESSION ON CYTOTOXIC LYMPHOCYTES BY RECOMBINANT MICA PROTEIN

Genome instability of transformed cells, being the most common factor of malignancy, may result into production of abnormal proteins in these cells. Normally, the newly formed proteins are recognized by immune system, thus causing elimination of the transformed cells. Nevertheless, the phenotypic in...

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Autores principales:	E. V. Abakushina, E. Yu. Lyssuk, A. V. Posvyatenko, A. V. Kibardin
Formato:	article
Lenguaje:	RU
Publicado:	SPb RAACI 2017
Materias:	nk cells nkg2d activating receptor nkg2d ligands stress-induced mica nkg2d inhibition Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/f461c65423e4433daebd24862474d12c
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spelling	oai:doaj.org-article:f461c65423e4433daebd24862474d12c2021-11-18T08:03:46ZINHIBITION OF THE NKG2D ACTIVATING RECEPTOR EXPRESSION ON CYTOTOXIC LYMPHOCYTES BY RECOMBINANT MICA PROTEIN1563-06252313-741X10.15789/1563-0625-2017-1-81-88https://doaj.org/article/f461c65423e4433daebd24862474d12c2017-01-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/1168https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XGenome instability of transformed cells, being the most common factor of malignancy, may result into production of abnormal proteins in these cells. Normally, the newly formed proteins are recognized by immune system, thus causing elimination of the transformed cells. Nevertheless, the phenotypic instability promotes formation of specific transformed cells which suppress effector immune reactions and/or are unrecognizable by cytotoxic lymphocytes. NKG2D is one of the most important activating receptors expressed by NK cells. It serves as a major recognition receptor for detection and elimination of tumor and infected cells. The ligands for NKG2D include surface or circulating non-canonical MICA/B molecules from class I major histocompatibility complex (MHC class I chain–related proteins A and B). MICA and MICB are expressed scarcely, if at all, by the most normal cells, being, however, upregulated in cancer cells and virus-infected cells.NKG2D receptor-ligand interaction is important for regulation of anti-tumor immune reactions. The soluble form of MICA accumulated in blood due to proteolytic shedding from tumor cell membranes is able to inhibit the NKG2D mediated anti-tumor cytotoxicyty and, therefore, promote the immune escape. The aim of our study was to estimate blocking effects of soluble recombinant human MICA protein (rhsMICA) upon NKG2D receptor of NK cells.Mononuclear cells were isolated from peripheral blood, followed by incubation with of rhsMICA at different concentrations (0, 1, 5, or 10 µg/ml), staining with anti-CD314 (NKG2D) mAbs on the CD3- CD56+NK cells, and flow cytometry analysis. A similar treatment protocol was applied for IL2- and IL15-activated mononuclear cells isolated from the melanoma patients.It has been shown that brief incubation of lymphocytes with rhsMICA caused a significantly reduced expression of NKG2D receptor on the surface of cytotoxic lymphocytes, both from healthy donors and melanoma patients. These changes depended on the MICA dose. Meanwhile, the cytokine-activated lymphocytes seem to become more resistant to inhibiting effects of rhsMICA, and, thus, do not cause any significant reduction of NKG2D expression on the activated NK cells. This fact may be a pre-requisite for usage of activated NK-cells for adoptive immunotherapy of cancer patients with MICA-positive malignancies.E. V. AbakushinaE. Yu. LyssukA. V. PosvyatenkoA. V. KibardinSPb RAACIarticlenk cellsnkg2d activating receptornkg2d ligandsstress-induced micankg2d inhibitionImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 19, Iss 1, Pp 81-88 (2017)
institution	DOAJ
collection	DOAJ
language	RU
topic	nk cells nkg2d activating receptor nkg2d ligands stress-induced mica nkg2d inhibition Immunologic diseases. Allergy RC581-607
spellingShingle	nk cells nkg2d activating receptor nkg2d ligands stress-induced mica nkg2d inhibition Immunologic diseases. Allergy RC581-607 E. V. Abakushina E. Yu. Lyssuk A. V. Posvyatenko A. V. Kibardin INHIBITION OF THE NKG2D ACTIVATING RECEPTOR EXPRESSION ON CYTOTOXIC LYMPHOCYTES BY RECOMBINANT MICA PROTEIN
description	Genome instability of transformed cells, being the most common factor of malignancy, may result into production of abnormal proteins in these cells. Normally, the newly formed proteins are recognized by immune system, thus causing elimination of the transformed cells. Nevertheless, the phenotypic instability promotes formation of specific transformed cells which suppress effector immune reactions and/or are unrecognizable by cytotoxic lymphocytes. NKG2D is one of the most important activating receptors expressed by NK cells. It serves as a major recognition receptor for detection and elimination of tumor and infected cells. The ligands for NKG2D include surface or circulating non-canonical MICA/B molecules from class I major histocompatibility complex (MHC class I chain–related proteins A and B). MICA and MICB are expressed scarcely, if at all, by the most normal cells, being, however, upregulated in cancer cells and virus-infected cells.NKG2D receptor-ligand interaction is important for regulation of anti-tumor immune reactions. The soluble form of MICA accumulated in blood due to proteolytic shedding from tumor cell membranes is able to inhibit the NKG2D mediated anti-tumor cytotoxicyty and, therefore, promote the immune escape. The aim of our study was to estimate blocking effects of soluble recombinant human MICA protein (rhsMICA) upon NKG2D receptor of NK cells.Mononuclear cells were isolated from peripheral blood, followed by incubation with of rhsMICA at different concentrations (0, 1, 5, or 10 µg/ml), staining with anti-CD314 (NKG2D) mAbs on the CD3- CD56+NK cells, and flow cytometry analysis. A similar treatment protocol was applied for IL2- and IL15-activated mononuclear cells isolated from the melanoma patients.It has been shown that brief incubation of lymphocytes with rhsMICA caused a significantly reduced expression of NKG2D receptor on the surface of cytotoxic lymphocytes, both from healthy donors and melanoma patients. These changes depended on the MICA dose. Meanwhile, the cytokine-activated lymphocytes seem to become more resistant to inhibiting effects of rhsMICA, and, thus, do not cause any significant reduction of NKG2D expression on the activated NK cells. This fact may be a pre-requisite for usage of activated NK-cells for adoptive immunotherapy of cancer patients with MICA-positive malignancies.
format	article
author	E. V. Abakushina E. Yu. Lyssuk A. V. Posvyatenko A. V. Kibardin
author_facet	E. V. Abakushina E. Yu. Lyssuk A. V. Posvyatenko A. V. Kibardin
author_sort	E. V. Abakushina
title	INHIBITION OF THE NKG2D ACTIVATING RECEPTOR EXPRESSION ON CYTOTOXIC LYMPHOCYTES BY RECOMBINANT MICA PROTEIN
title_short	INHIBITION OF THE NKG2D ACTIVATING RECEPTOR EXPRESSION ON CYTOTOXIC LYMPHOCYTES BY RECOMBINANT MICA PROTEIN
title_full	INHIBITION OF THE NKG2D ACTIVATING RECEPTOR EXPRESSION ON CYTOTOXIC LYMPHOCYTES BY RECOMBINANT MICA PROTEIN
title_fullStr	INHIBITION OF THE NKG2D ACTIVATING RECEPTOR EXPRESSION ON CYTOTOXIC LYMPHOCYTES BY RECOMBINANT MICA PROTEIN
title_full_unstemmed	INHIBITION OF THE NKG2D ACTIVATING RECEPTOR EXPRESSION ON CYTOTOXIC LYMPHOCYTES BY RECOMBINANT MICA PROTEIN
title_sort	inhibition of the nkg2d activating receptor expression on cytotoxic lymphocytes by recombinant mica protein
publisher	SPb RAACI
publishDate	2017
url	https://doaj.org/article/f461c65423e4433daebd24862474d12c
work_keys_str_mv	AT evabakushina inhibitionofthenkg2dactivatingreceptorexpressiononcytotoxiclymphocytesbyrecombinantmicaprotein AT eyulyssuk inhibitionofthenkg2dactivatingreceptorexpressiononcytotoxiclymphocytesbyrecombinantmicaprotein AT avposvyatenko inhibitionofthenkg2dactivatingreceptorexpressiononcytotoxiclymphocytesbyrecombinantmicaprotein AT avkibardin inhibitionofthenkg2dactivatingreceptorexpressiononcytotoxiclymphocytesbyrecombinantmicaprotein
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INHIBITION OF THE NKG2D ACTIVATING RECEPTOR EXPRESSION ON CYTOTOXIC LYMPHOCYTES BY RECOMBINANT MICA PROTEIN

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