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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | Russian |
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St. Petersburg branch of the Russian Association of Allergologists and Clinical Immunologists
2017-01-01
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| Series: | Медицинская иммунология |
| Subjects: | |
| Online Access: | https://www.mimmun.ru/mimmun/article/view/1168 |
| _version_ | 1797197989263966208 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-08T05:50:14Z |
| format | Article |
| id | doaj.art-f461c65423e4433daebd24862474d12c |
| institution | Directory Open Access Journal |
| issn | 1563-0625 2313-741X |
| language | Russian |
| last_indexed | 2024-04-24T06:52:43Z |
| publishDate | 2017-01-01 |
| publisher | St. Petersburg branch of the Russian Association of Allergologists and Clinical Immunologists |
| record_format | Article |
| series | Медицинская иммунология |
| spelling | doaj.art-f461c65423e4433daebd24862474d12c2024-04-22T13:07:41ZrusSt. Petersburg branch of the Russian Association of Allergologists and Clinical ImmunologistsМедицинская иммунология1563-06252313-741X2017-01-01191818810.15789/1563-0625-2017-1-81-88885INHIBITION OF THE NKG2D ACTIVATING RECEPTOR EXPRESSION ON CYTOTOXIC LYMPHOCYTES BY RECOMBINANT MICA PROTEINE. V. Abakushina0E. Yu. Lyssuk1A. V. Posvyatenko2A. V. Kibardin3Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological CentreInstitute of Gene Biology, Russian Academy of Sciences; Dmitry Rogachev Federal Research Center of Pediatric Hematology, Oncology and ImmunologyInstitute of Gene Biology, Russian Academy of Sciences; Dmitry Rogachev Federal Research Center of Pediatric Hematology, Oncology and Immunology; N. Pirogov Russian National Research Medical UniversityInstitute of Gene Biology, Russian Academy of Sciences; Dmitry Rogachev Federal Research Center of Pediatric Hematology, Oncology and ImmunologyGenome 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.https://www.mimmun.ru/mimmun/article/view/1168nk cellsnkg2d activating receptornkg2d ligandsstress-induced micankg2d inhibition |
| spellingShingle | 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 Медицинская иммунология nk cells nkg2d activating receptor nkg2d ligands stress-induced mica nkg2d inhibition |
| title | 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_short | 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 |
| topic | nk cells nkg2d activating receptor nkg2d ligands stress-induced mica nkg2d inhibition |
| url | https://www.mimmun.ru/mimmun/article/view/1168 |
| work_keys_str_mv | AT evabakushina inhibitionofthenkg2dactivatingreceptorexpressiononcytotoxiclymphocytesbyrecombinantmicaprotein AT eyulyssuk inhibitionofthenkg2dactivatingreceptorexpressiononcytotoxiclymphocytesbyrecombinantmicaprotein AT avposvyatenko inhibitionofthenkg2dactivatingreceptorexpressiononcytotoxiclymphocytesbyrecombinantmicaprotein AT avkibardin inhibitionofthenkg2dactivatingreceptorexpressiononcytotoxiclymphocytesbyrecombinantmicaprotein |