Molecular Basis for LLT1 Protein Recognition by Human CD161 Protein (NKRP1A/KLRB1)
Human Th17 cells express high levels of CD161, a member of the killer cell lectin-like receptor (KLR) family (also referred to as NK receptor-P1A (NKRP1A) or KLRB1), as a representative marker. CD161 is also expressed on natural killer (NK) cells and NKT cells. Lectin-like transcript 1 (LLT1), anoth...
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description | Human Th17 cells express high levels of CD161, a member of the killer cell lectin-like receptor (KLR) family (also referred to as NK receptor-P1A (NKRP1A) or KLRB1), as a representative marker. CD161 is also expressed on natural killer (NK) cells and NKT cells. Lectin-like transcript 1 (LLT1), another KLR family member, was recently identified as a ligand for CD161. This interaction may play pivotal roles in the immunomodulatory functions of Th17 cells as well as those of NK and NKT cells. However, the molecular basis for the interaction is poorly understood. Here we show that the extracellular domain of CD161 bound directly to LLT1 with a Kd of 48 μm and with the fast kinetics typical of cell-cell recognition receptors. Mutagenesis revealed that the similar membrane-distal β-sheet and loop regions of both CD161 and LLT1 were utilized for the binding, and notably, these regions correspond to the ligand-binding sites for major histocompatibility complex (MHC)-recognizing KLRs. Furthermore, we found a pair of detrimental mutations for both molecules that restored the binding. These results reveal a new template model for the recognition mode between the KLR family members and provide insights into the molecular mechanism underlying Th17/NK/NKT-mediated immune responses. |
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CD161 is also expressed on natural killer (NK) cells and NKT cells. Lectin-like transcript 1 (LLT1), another KLR family member, was recently identified as a ligand for CD161. This interaction may play pivotal roles in the immunomodulatory functions of Th17 cells as well as those of NK and NKT cells. However, the molecular basis for the interaction is poorly understood. Here we show that the extracellular domain of CD161 bound directly to LLT1 with a Kd of 48 μm and with the fast kinetics typical of cell-cell recognition receptors. Mutagenesis revealed that the similar membrane-distal β-sheet and loop regions of both CD161 and LLT1 were utilized for the binding, and notably, these regions correspond to the ligand-binding sites for major histocompatibility complex (MHC)-recognizing KLRs. Furthermore, we found a pair of detrimental mutations for both molecules that restored the binding. These results reveal a new template model for the recognition mode between the KLR family members and provide insights into the molecular mechanism underlying Th17/NK/NKT-mediated immune responses.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M110.214254</identifier><identifier>PMID: 21572041</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>C-type Lectin-like Receptors ; CD161 ; Cell Surface Receptor ; HEK293 Cells ; Histocompatibility Antigens - genetics ; Histocompatibility Antigens - immunology ; Histocompatibility Antigens - metabolism ; Humans ; Immunology ; Immunosupressor ; Killer Cells, Natural - cytology ; Killer Cells, Natural - immunology ; Killer Cells, Natural - metabolism ; Lectins, C-Type - genetics ; Lectins, C-Type - immunology ; Lectins, C-Type - metabolism ; MHC ; Mutation ; Natural Killer Cells ; Natural Killer T-Cells - cytology ; Natural Killer T-Cells - immunology ; Natural Killer T-Cells - metabolism ; NK Cell Lectin-Like Receptor Subfamily B - genetics ; NK Cell Lectin-Like Receptor Subfamily B - immunology ; NK Cell Lectin-Like Receptor Subfamily B - metabolism ; NKRP1 ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein-Protein Interactions ; Receptors, Cell Surface - genetics ; Receptors, Cell Surface - immunology ; Receptors, Cell Surface - metabolism ; Surface Plasmon Resonance (SPR) ; Th17 Cell ; Th17 Cells - cytology ; Th17 Cells - immunology ; Th17 Cells - metabolism</subject><ispartof>The Journal of biological chemistry, 2011-07, Vol.286 (27), p.23823-23830</ispartof><rights>2011 © 2011 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><rights>2011 by The American Society for Biochemistry and Molecular Biology, Inc. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c508t-ef2a55480c009f645b254bdc5c8500a20eb7bb8a55b33eef488adafd0d1ed5f13</citedby><cites>FETCH-LOGICAL-c508t-ef2a55480c009f645b254bdc5c8500a20eb7bb8a55b33eef488adafd0d1ed5f13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3129164/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3129164/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21572041$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kamishikiryo, Jun</creatorcontrib><creatorcontrib>Fukuhara, Hideo</creatorcontrib><creatorcontrib>Okabe, Yuki</creatorcontrib><creatorcontrib>Kuroki, Kimiko</creatorcontrib><creatorcontrib>Maenaka, Katsumi</creatorcontrib><title>Molecular Basis for LLT1 Protein Recognition by Human CD161 Protein (NKRP1A/KLRB1)</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Human Th17 cells express high levels of CD161, a member of the killer cell lectin-like receptor (KLR) family (also referred to as NK receptor-P1A (NKRP1A) or KLRB1), as a representative marker. CD161 is also expressed on natural killer (NK) cells and NKT cells. Lectin-like transcript 1 (LLT1), another KLR family member, was recently identified as a ligand for CD161. This interaction may play pivotal roles in the immunomodulatory functions of Th17 cells as well as those of NK and NKT cells. However, the molecular basis for the interaction is poorly understood. Here we show that the extracellular domain of CD161 bound directly to LLT1 with a Kd of 48 μm and with the fast kinetics typical of cell-cell recognition receptors. Mutagenesis revealed that the similar membrane-distal β-sheet and loop regions of both CD161 and LLT1 were utilized for the binding, and notably, these regions correspond to the ligand-binding sites for major histocompatibility complex (MHC)-recognizing KLRs. Furthermore, we found a pair of detrimental mutations for both molecules that restored the binding. These results reveal a new template model for the recognition mode between the KLR family members and provide insights into the molecular mechanism underlying Th17/NK/NKT-mediated immune responses.</description><subject>C-type Lectin-like Receptors</subject><subject>CD161</subject><subject>Cell Surface Receptor</subject><subject>HEK293 Cells</subject><subject>Histocompatibility Antigens - genetics</subject><subject>Histocompatibility Antigens - immunology</subject><subject>Histocompatibility Antigens - metabolism</subject><subject>Humans</subject><subject>Immunology</subject><subject>Immunosupressor</subject><subject>Killer Cells, Natural - cytology</subject><subject>Killer Cells, Natural - immunology</subject><subject>Killer Cells, Natural - metabolism</subject><subject>Lectins, C-Type - genetics</subject><subject>Lectins, C-Type - immunology</subject><subject>Lectins, C-Type - metabolism</subject><subject>MHC</subject><subject>Mutation</subject><subject>Natural Killer Cells</subject><subject>Natural Killer T-Cells - cytology</subject><subject>Natural Killer T-Cells - immunology</subject><subject>Natural Killer T-Cells - metabolism</subject><subject>NK Cell Lectin-Like Receptor Subfamily B - genetics</subject><subject>NK Cell Lectin-Like Receptor Subfamily B - immunology</subject><subject>NK Cell Lectin-Like Receptor Subfamily B - metabolism</subject><subject>NKRP1</subject><subject>Protein Structure, Secondary</subject><subject>Protein Structure, Tertiary</subject><subject>Protein-Protein Interactions</subject><subject>Receptors, Cell Surface - genetics</subject><subject>Receptors, Cell Surface - immunology</subject><subject>Receptors, Cell Surface - metabolism</subject><subject>Surface Plasmon Resonance (SPR)</subject><subject>Th17 Cell</subject><subject>Th17 Cells - cytology</subject><subject>Th17 Cells - immunology</subject><subject>Th17 Cells - metabolism</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kD1PwzAQhi0EglKY2VBGGNL6HLtNFiRaPopIoapAYrNs5wJGaVw5KRL_Hlflc8DLybrn3tM9hBwB7QEd8v6rNr0phB8DzgTfIh2gaRInAp62SYdSBnHGRLpH9pvmlYbHM9glewzEkFEOHTKfugrNqlI-GqnGNlHpfJTnDxDNvGvR1tEcjXuubWtdHen3aLJaqDoaX8DgBzm5u53P4Lx_m89HcHpAdkpVNXj4Wbvk8eryYTyJ8_vrm_F5HhtB0zbGkikheEoNpVk54EKHA3RhhEkFpYpR1EOt08DoJEEseZqqQpUFLQALUULSJWeb3OVKL7AwWLdeVXLp7UL5d-mUlX87tX2Rz-5NJsAyGPAQ0N8EGO-axmP5PQtUrvXKoFeu9cqN3jBx_HvlN__lMwDZBsBw-JtFLxtjsTZYWI-mlYWz_4Z_APxNiHg</recordid><startdate>20110708</startdate><enddate>20110708</enddate><creator>Kamishikiryo, Jun</creator><creator>Fukuhara, Hideo</creator><creator>Okabe, Yuki</creator><creator>Kuroki, Kimiko</creator><creator>Maenaka, Katsumi</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</scope><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>5PM</scope></search><sort><creationdate>20110708</creationdate><title>Molecular Basis for LLT1 Protein Recognition by Human CD161 Protein (NKRP1A/KLRB1)</title><author>Kamishikiryo, Jun ; Fukuhara, Hideo ; Okabe, Yuki ; Kuroki, Kimiko ; Maenaka, Katsumi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c508t-ef2a55480c009f645b254bdc5c8500a20eb7bb8a55b33eef488adafd0d1ed5f13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>C-type Lectin-like Receptors</topic><topic>CD161</topic><topic>Cell Surface Receptor</topic><topic>HEK293 Cells</topic><topic>Histocompatibility Antigens - genetics</topic><topic>Histocompatibility Antigens - immunology</topic><topic>Histocompatibility Antigens - metabolism</topic><topic>Humans</topic><topic>Immunology</topic><topic>Immunosupressor</topic><topic>Killer Cells, Natural - cytology</topic><topic>Killer Cells, Natural - immunology</topic><topic>Killer Cells, Natural - metabolism</topic><topic>Lectins, C-Type - genetics</topic><topic>Lectins, C-Type - immunology</topic><topic>Lectins, C-Type - metabolism</topic><topic>MHC</topic><topic>Mutation</topic><topic>Natural Killer Cells</topic><topic>Natural Killer T-Cells - cytology</topic><topic>Natural Killer T-Cells - immunology</topic><topic>Natural Killer T-Cells - metabolism</topic><topic>NK Cell Lectin-Like Receptor Subfamily B - genetics</topic><topic>NK Cell Lectin-Like Receptor Subfamily B - immunology</topic><topic>NK Cell Lectin-Like Receptor Subfamily B - metabolism</topic><topic>NKRP1</topic><topic>Protein Structure, Secondary</topic><topic>Protein Structure, Tertiary</topic><topic>Protein-Protein Interactions</topic><topic>Receptors, Cell Surface - genetics</topic><topic>Receptors, Cell Surface - immunology</topic><topic>Receptors, Cell Surface - metabolism</topic><topic>Surface Plasmon Resonance (SPR)</topic><topic>Th17 Cell</topic><topic>Th17 Cells - cytology</topic><topic>Th17 Cells - immunology</topic><topic>Th17 Cells - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kamishikiryo, Jun</creatorcontrib><creatorcontrib>Fukuhara, Hideo</creatorcontrib><creatorcontrib>Okabe, Yuki</creatorcontrib><creatorcontrib>Kuroki, Kimiko</creatorcontrib><creatorcontrib>Maenaka, Katsumi</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kamishikiryo, Jun</au><au>Fukuhara, Hideo</au><au>Okabe, Yuki</au><au>Kuroki, Kimiko</au><au>Maenaka, Katsumi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular Basis for LLT1 Protein Recognition by Human CD161 Protein (NKRP1A/KLRB1)</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2011-07-08</date><risdate>2011</risdate><volume>286</volume><issue>27</issue><spage>23823</spage><epage>23830</epage><pages>23823-23830</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Human Th17 cells express high levels of CD161, a member of the killer cell lectin-like receptor (KLR) family (also referred to as NK receptor-P1A (NKRP1A) or KLRB1), as a representative marker. CD161 is also expressed on natural killer (NK) cells and NKT cells. Lectin-like transcript 1 (LLT1), another KLR family member, was recently identified as a ligand for CD161. This interaction may play pivotal roles in the immunomodulatory functions of Th17 cells as well as those of NK and NKT cells. However, the molecular basis for the interaction is poorly understood. Here we show that the extracellular domain of CD161 bound directly to LLT1 with a Kd of 48 μm and with the fast kinetics typical of cell-cell recognition receptors. Mutagenesis revealed that the similar membrane-distal β-sheet and loop regions of both CD161 and LLT1 were utilized for the binding, and notably, these regions correspond to the ligand-binding sites for major histocompatibility complex (MHC)-recognizing KLRs. Furthermore, we found a pair of detrimental mutations for both molecules that restored the binding. 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subjects | C-type Lectin-like Receptors CD161 Cell Surface Receptor HEK293 Cells Histocompatibility Antigens - genetics Histocompatibility Antigens - immunology Histocompatibility Antigens - metabolism Humans Immunology Immunosupressor Killer Cells, Natural - cytology Killer Cells, Natural - immunology Killer Cells, Natural - metabolism Lectins, C-Type - genetics Lectins, C-Type - immunology Lectins, C-Type - metabolism MHC Mutation Natural Killer Cells Natural Killer T-Cells - cytology Natural Killer T-Cells - immunology Natural Killer T-Cells - metabolism NK Cell Lectin-Like Receptor Subfamily B - genetics NK Cell Lectin-Like Receptor Subfamily B - immunology NK Cell Lectin-Like Receptor Subfamily B - metabolism NKRP1 Protein Structure, Secondary Protein Structure, Tertiary Protein-Protein Interactions Receptors, Cell Surface - genetics Receptors, Cell Surface - immunology Receptors, Cell Surface - metabolism Surface Plasmon Resonance (SPR) Th17 Cell Th17 Cells - cytology Th17 Cells - immunology Th17 Cells - metabolism |
title | Molecular Basis for LLT1 Protein Recognition by Human CD161 Protein (NKRP1A/KLRB1) |
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