{"created":"2024-10-29T00:53:19.752667+00:00","id":2006709,"links":{},"metadata":{"_buckets":{"deposit":"6527db76-9912-46ab-9a47-6bcf8ba4c612"},"_deposit":{"created_by":7,"id":"2006709","owners":[7],"pid":{"revision_id":0,"type":"depid","value":"2006709"},"status":"published"},"_oai":{"id":"oai:tokushima-u.repo.nii.ac.jp:02006709","sets":["1713853213384:1713853296295:1716267876683:1716268551628"]},"author_link":["346","315"],"item_10001_alternative_title_1":{"attribute_name":"タイトル別表記","attribute_value_mlt":[{"subitem_alternative_title":"抑制性免疫補助受容体LAG-3は細胞質領域に有する非定型モチーフを介してT細胞の活性化を抑制する","subitem_alternative_title_language":"ja"},{"subitem_alternative_title":"Inhibitory mechanisms of LAG-3–dependent T cell suppression","subitem_alternative_title_language":"en"}]},"item_10001_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2019-02-13","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"15","bibliographicPageEnd":"6026","bibliographicPageStart":"6017","bibliographicVolumeNumber":"294","bibliographic_titles":[{"bibliographic_title":"Journal of Biological Chemistry","bibliographic_titleLang":"en"}]}]},"item_10001_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"T cell activation is tightly regulated by both stimulatory and inhibitory co-receptors and has been a focus in the development of interventions for managing cancer or autoimmune diseases. Targeting the inhibitory co-receptors programmed cell death 1 (PD-1) and cytotoxic T lymphocyte–associated protein 4 (CTLA-4) has successfully eradicated tumors but induced immune-related adverse events in humans and mice. The beneficial and adverse effects of targeting these co-receptors highlight their importance in cancer immunity and also autoimmunity. Although the therapeutic potencies of other inhibitory co-receptors are under extensive investigation, their inhibitory mechanisms and their functional differences are not well understood. Here we analyzed the inhibitory mechanisms of lymphocyte activation gene-3 (LAG-3), another inhibitory co-receptor, by using an in vitro T cell activation system and a high-affinity anti-LAG-3 antibody that strongly interferes with the binding of LAG-3 to its ligand. We found that the expression level of LAG-3 strongly correlates with the inhibitory function of LAG-3, suggesting that LAG-3 functions as a rheostat rather than as a breaker of T cell activation. By evaluating the inhibitory capacities of various LAG-3 variants relative to their expression levels, we found that LAG-3 transduces two independent inhibitory signals through an FXXL motif in the membrane-proximal region and the C-terminal EX repeat. These motifs have not been reported previously for inhibitory co-receptors, suggesting that LAG-3 inhibits T cell activation through a nonredundant inhibitory mechanisms along with the other inhibitory co-receptors. Our findings provide a rationale for combinatorial targeting of LAG-3 and the other inhibitory co-receptors to improve cancer immunotherapy.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_10001_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"American Society for Biochemistry and Molecular Biology","subitem_publisher_language":"en"}]},"item_10001_rights_15":{"attribute_name":"権利情報","attribute_value_mlt":[{"subitem_rights":"© 2019 Maeda et al. Published under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc.","subitem_rights_language":"en"}]},"item_10001_source_id_9":{"attribute_name":"収録物ID","attribute_value_mlt":[{"subitem_source_identifier":"1083351X","subitem_source_identifier_type":"ISSN"},{"subitem_source_identifier":"AA1202441X","subitem_source_identifier_type":"NCID"}]},"item_10001_version_type_20":{"attribute_name":"出版タイプ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_be7fb7dd8ff6fe43","subitem_version_type":"NA"}]},"item_1714461018643":{"attribute_name":"報告番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第3319号"}]},"item_1714461102074":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（医学）","subitem_degreename_language":"ja"}]},"item_1714461118377":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2019-06-27"}]},"item_1714461137393":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"徳島大学"}]}]},"item_1715043197608":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access"}]},"item_1718868208704":{"attribute_name":"備考","attribute_value_mlt":[{"subitem_textarea_language":"ja","subitem_textarea_value":"内容要旨・審査要旨・論文本文の公開\n本論文は，著者Takeo K. Maedaの学位論文として提出され，学位審査・授与の対象となっている。\nThis research was originally published in the Journal of Biological Chemistry. Takeo K. Maeda, Daisuke Sugiura, Il-mi Okazaki, Takumi Maruhashi, Taku Okazaki. Atypical motifs in the cytoplasmic region of the inhibitory immune co-receptor LAG-3 inhibit T cell activation. J. Biol. Chem. 2019 Vol.294(15), pp.6017-6026.\n学位授与者所属 : 徳島大学大学院医科学教育部（医学専攻）"}]},"item_1718868303842":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_text_language":"ja","subitem_text_value":"甲医第1421号"}]},"item_1722929371688":{"attribute_name":"出版社版DOI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_language":"ja","subitem_relation_name_text":"10.1074/jbc.RA119.007455"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1074/jbc.RA119.007455","subitem_relation_type_select":"DOI"}}]},"item_1723180141928":{"attribute_name":"EID","attribute_value_mlt":[{"subitem_identifier_type":"URI","subitem_identifier_uri":"356654"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"前田, 武雄","creatorNameLang":"ja"},{"creatorName":"マエダ, タケオ","creatorNameLang":"ja-Kana"},{"creatorName":"Maeda, Takeo K.","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"杉浦, 大祐","creatorNameLang":"ja"},{"creatorName":"スギウラ, ダイスケ","creatorNameLang":"ja-Kana"},{"creatorName":"Sugiura, Daisuke","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"岡崎, 一美","creatorNameLang":"ja"}],"nameIdentifiers":[{"nameIdentifier":"346","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"丸橋, 拓海","creatorNameLang":"ja"},{"creatorName":"マルハシ, タクミ","creatorNameLang":"ja-Kana"},{"creatorName":"Maruhashi, Takumi","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"岡崎, 拓","creatorNameLang":"ja"}],"nameIdentifiers":[{"nameIdentifier":"315","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2019-09-03"}],"displaytype":"detail","filename":"k3319_abstract.pdf","filesize":[{"value":"142 KB"}],"format":"application/pdf","mimetype":"application/pdf","url":{"objectType":"abstract","url":"https://tokushima-u.repo.nii.ac.jp/record/2006709/files/k3319_abstract.pdf"},"version_id":"9c64e81c-3bcb-4be7-8728-012ec15b6dfd"},{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2019-09-03"}],"displaytype":"detail","filename":"k3319_review.pdf","filesize":[{"value":"93.3 KB"}],"format":"application/pdf","mimetype":"application/pdf","url":{"objectType":"other","url":"https://tokushima-u.repo.nii.ac.jp/record/2006709/files/k3319_review.pdf"},"version_id":"aebd46f5-56cb-4a1e-aab8-3b4343c16233"},{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2020-02-19"}],"displaytype":"detail","filename":"k3319_fulltext.pdf","filesize":[{"value":"3.29 MB"}],"format":"application/pdf","mimetype":"application/pdf","url":{"objectType":"fulltext","url":"https://tokushima-u.repo.nii.ac.jp/record/2006709/files/k3319_fulltext.pdf"},"version_id":"70c7a274-eeeb-437d-8281-3a7c1646bb4d"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"T細胞抗原受容体","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"免疫補助受容体","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"抑制機構","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"モノクローナル抗体","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"LAG-3","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"Atypical motifs in the cytoplasmic region of the inhibitory immune co-receptor LAG-3 inhibit T cell activation","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Atypical motifs in the cytoplasmic region of the inhibitory immune co-receptor LAG-3 inhibit T cell activation","subitem_title_language":"en"}]},"item_type_id":"40001","owner":"7","path":["1716268551628"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2019-09-03"},"publish_date":"2019-09-03","publish_status":"0","recid":"2006709","relation_version_is_last":true,"title":["Atypical motifs in the cytoplasmic region of the inhibitory immune co-receptor LAG-3 inhibit T cell activation"],"weko_creator_id":"7","weko_shared_id":-1},"updated":"2024-10-29T00:53:30.947258+00:00"}