Natural killer cell education in mice with single or multiple major histocompatibility complex class I molecules
The ability of murine NK cells to reject cells lacking self MHC class I expression results from an in vivo education process. To study the impact of individual MHC class I alleles on this process, we generated mice expressing single MHC class I alleles (K(b), D(b), D(d), or L(d)) or combinations of...
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Veröffentlicht in: | The Journal of experimental medicine 2005-04, Vol.201 (7), p.1145-1155 |
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creator | Johansson, Sofia Johansson, Maria Rosmaraki, Eleftheria Vahlne, Gustaf Mehr, Ramit Salmon-Divon, Mali Lemonnier, François Kärre, Klas Höglund, Petter |
description | The ability of murine NK cells to reject cells lacking self MHC class I expression results from an in vivo education process. To study the impact of individual MHC class I alleles on this process, we generated mice expressing single MHC class I alleles (K(b), D(b), D(d), or L(d)) or combinations of two or more alleles. All single MHC class I mice rejected MHC class I-deficient cells in an NK cell-dependent way. Expression of K(b) or D(d) conveyed strong rejection of MHC class I-deficient cells, whereas the expression of D(b) or L(d) resulted in weaker responses. The educating impact of weak ligands (D(b) and L(d)) was further attenuated by the introduction of additional MHC class I alleles, whereas strong ligands (K(b) and D(d)) maintained their educating impact under such conditions. An analysis of activating and inhibitory receptors in single MHC class I mice suggested that the educating impact of a given MHC class I molecule was controlled both by the number of NK cells affected and by the strength of each MHC class I-Ly49 receptor interaction, indicating that NK cell education may be regulated by a combination of qualitative and quantitative events. |
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To study the impact of individual MHC class I alleles on this process, we generated mice expressing single MHC class I alleles (K(b), D(b), D(d), or L(d)) or combinations of two or more alleles. All single MHC class I mice rejected MHC class I-deficient cells in an NK cell-dependent way. Expression of K(b) or D(d) conveyed strong rejection of MHC class I-deficient cells, whereas the expression of D(b) or L(d) resulted in weaker responses. The educating impact of weak ligands (D(b) and L(d)) was further attenuated by the introduction of additional MHC class I alleles, whereas strong ligands (K(b) and D(d)) maintained their educating impact under such conditions. An analysis of activating and inhibitory receptors in single MHC class I mice suggested that the educating impact of a given MHC class I molecule was controlled both by the number of NK cells affected and by the strength of each MHC class I-Ly49 receptor interaction, indicating that NK cell education may be regulated by a combination of qualitative and quantitative events.</description><identifier>ISSN: 0022-1007</identifier><identifier>EISSN: 1540-9538</identifier><identifier>EISSN: 1892-1007</identifier><identifier>DOI: 10.1084/jem.20050167</identifier><identifier>PMID: 15809355</identifier><language>eng</language><publisher>United States: The Rockefeller University Press</publisher><subject>Alleles ; Animals ; Antigens, Ly - metabolism ; Down-Regulation ; Flow Cytometry ; Fluoresceins ; Histocompatibility Antigens Class I - genetics ; Histocompatibility Antigens Class I - metabolism ; Killer Cells, Natural - metabolism ; Lectins, C-Type ; Mice ; Mice, Transgenic ; Receptors, Immunologic - metabolism ; Receptors, Natural Killer Cell ; Receptors, NK Cell Lectin-Like ; Self Tolerance - genetics ; Self Tolerance - immunology ; Succinimides</subject><ispartof>The Journal of experimental medicine, 2005-04, Vol.201 (7), p.1145-1155</ispartof><rights>Copyright © 2005, The Rockefeller University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c451t-3eeb5443bd93bdbdbf5a1322db310851cd1206f004c1e7912ea7d8f9286067e53</citedby><cites>FETCH-LOGICAL-c451t-3eeb5443bd93bdbdbf5a1322db310851cd1206f004c1e7912ea7d8f9286067e53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,550,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15809355$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:1948718$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Johansson, Sofia</creatorcontrib><creatorcontrib>Johansson, Maria</creatorcontrib><creatorcontrib>Rosmaraki, Eleftheria</creatorcontrib><creatorcontrib>Vahlne, Gustaf</creatorcontrib><creatorcontrib>Mehr, Ramit</creatorcontrib><creatorcontrib>Salmon-Divon, Mali</creatorcontrib><creatorcontrib>Lemonnier, François</creatorcontrib><creatorcontrib>Kärre, Klas</creatorcontrib><creatorcontrib>Höglund, Petter</creatorcontrib><title>Natural killer cell education in mice with single or multiple major histocompatibility complex class I molecules</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><description>The ability of murine NK cells to reject cells lacking self MHC class I expression results from an in vivo education process. To study the impact of individual MHC class I alleles on this process, we generated mice expressing single MHC class I alleles (K(b), D(b), D(d), or L(d)) or combinations of two or more alleles. All single MHC class I mice rejected MHC class I-deficient cells in an NK cell-dependent way. Expression of K(b) or D(d) conveyed strong rejection of MHC class I-deficient cells, whereas the expression of D(b) or L(d) resulted in weaker responses. The educating impact of weak ligands (D(b) and L(d)) was further attenuated by the introduction of additional MHC class I alleles, whereas strong ligands (K(b) and D(d)) maintained their educating impact under such conditions. An analysis of activating and inhibitory receptors in single MHC class I mice suggested that the educating impact of a given MHC class I molecule was controlled both by the number of NK cells affected and by the strength of each MHC class I-Ly49 receptor interaction, indicating that NK cell education may be regulated by a combination of qualitative and quantitative events.</description><subject>Alleles</subject><subject>Animals</subject><subject>Antigens, Ly - metabolism</subject><subject>Down-Regulation</subject><subject>Flow Cytometry</subject><subject>Fluoresceins</subject><subject>Histocompatibility Antigens Class I - genetics</subject><subject>Histocompatibility Antigens Class I - metabolism</subject><subject>Killer Cells, Natural - metabolism</subject><subject>Lectins, C-Type</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Receptors, Immunologic - metabolism</subject><subject>Receptors, Natural Killer Cell</subject><subject>Receptors, NK Cell Lectin-Like</subject><subject>Self Tolerance - genetics</subject><subject>Self Tolerance - immunology</subject><subject>Succinimides</subject><issn>0022-1007</issn><issn>1540-9538</issn><issn>1892-1007</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNqFkctvFDEMhyMEotvCjTPKiRNTnNc8LkioglKpgguco0zG0802mQyTTEv_e7La5dETSqLY8Wcr9o-QVwzOGbTy3Q7DOQdQwOrmCdkwJaHqlGifkg0A5xUDaE7IaUo7ACalqp-TE6Za6IRSGzJ_MXldjKe3zntcqEXvKQ6rNdnFibqJBmeR3ru8pclNNx5pXGhYfXZzsYPZFXfrUo42hrkk9c67_ED3nsef1HqTEr2iIXq0q8f0gjwbjU_48nifke-fPn67-Fxdf728uvhwXVmpWK4EYq-kFP3QlVPWqAwTnA-9KF0rZgfGoR4BpGXYdIyjaYZ27HhbQ92gEmekOtRN9zivvZ4XF8zyoKNx-vh0WyzUqmUS6sK_P_AlEnCwOOUylkdpjyOT2-qbeKc5Z4LxfYE3xwJL_LFiyjq4tB-nmTCuSddNA6qw_wVZ0za87AK-PYB2iSktOP75DQO9114X7fVv7Qv--t8O_sJHscUvHMGtyw</recordid><startdate>20050404</startdate><enddate>20050404</enddate><creator>Johansson, Sofia</creator><creator>Johansson, Maria</creator><creator>Rosmaraki, Eleftheria</creator><creator>Vahlne, Gustaf</creator><creator>Mehr, Ramit</creator><creator>Salmon-Divon, Mali</creator><creator>Lemonnier, François</creator><creator>Kärre, Klas</creator><creator>Höglund, Petter</creator><general>The Rockefeller University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20050404</creationdate><title>Natural killer cell education in mice with single or multiple major histocompatibility complex class I molecules</title><author>Johansson, Sofia ; 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To study the impact of individual MHC class I alleles on this process, we generated mice expressing single MHC class I alleles (K(b), D(b), D(d), or L(d)) or combinations of two or more alleles. All single MHC class I mice rejected MHC class I-deficient cells in an NK cell-dependent way. Expression of K(b) or D(d) conveyed strong rejection of MHC class I-deficient cells, whereas the expression of D(b) or L(d) resulted in weaker responses. The educating impact of weak ligands (D(b) and L(d)) was further attenuated by the introduction of additional MHC class I alleles, whereas strong ligands (K(b) and D(d)) maintained their educating impact under such conditions. 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subjects | Alleles Animals Antigens, Ly - metabolism Down-Regulation Flow Cytometry Fluoresceins Histocompatibility Antigens Class I - genetics Histocompatibility Antigens Class I - metabolism Killer Cells, Natural - metabolism Lectins, C-Type Mice Mice, Transgenic Receptors, Immunologic - metabolism Receptors, Natural Killer Cell Receptors, NK Cell Lectin-Like Self Tolerance - genetics Self Tolerance - immunology Succinimides |
title | Natural killer cell education in mice with single or multiple major histocompatibility complex class I molecules |
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