{"id":15570,"date":"2020-06-08T18:25:58","date_gmt":"2020-06-08T17:25:58","guid":{"rendered":"https:\/\/cri1149.fr\/?post_type=publications&p=15570"},"modified":"2025-09-11T16:48:01","modified_gmt":"2025-09-11T14:48:01","slug":"decouverte-de-nouveaux-acteurs-dans-lactivation-des-lymphocytes-t","status":"publish","type":"publication","link":"https:\/\/cri1149.fr\/en\/publication\/decouverte-de-nouveaux-acteurs-dans-lactivation-des-lymphocytes-t\/","title":{"rendered":"New players in the activation of T Lymphocytes"},"content":{"rendered":"","protected":false},"featured_media":15572,"template":"","meta":{"_acf_changed":false,"_EventAllDay":false,"_EventTimezone":"","_EventStartDate":"","_EventEndDate":"","_EventStartDateUTC":"","_EventEndDateUTC":"","_EventShowMap":false,"_EventShowMapLink":false,"_EventURL":"","_EventCost":"","_EventCostDescription":"","_EventCurrencySymbol":"","_EventCurrencyCode":"","_EventCurrencyPosition":"","_EventDateTimeSeparator":"","_EventTimeRangeSeparator":"","_EventOrganizerID":[],"_EventVenueID":[],"_OrganizerEmail":"","_OrganizerPhone":"","_OrganizerWebsite":"","_VenueAddress":"","_VenueCity":"","_VenueCountry":"","_VenueProvince":"","_VenueState":"","_VenueZip":"","_VenuePhone":"","_VenueURL":"","_VenueStateProvince":"","_VenueLat":"","_VenueLng":"","_VenueShowMap":false,"_VenueShowMapLink":false},"category_publication":[],"class_list":["post-15570","publication","type-publication","status-publish","has-post-thumbnail","hentry"],"acf":{"numero_de_publication":"Nature Communications","date_de_publication":"20200602","numero_doi":"","equipe":[155],"auteurs-liste":[{"texte_libre":false,"auteur-lien":13182,"auteur-text":[]},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Pascal Chappert"},{"texte_libre":false,"auteur-lien":13032,"auteur-text":[]},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Andres Zucchetti"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Mirjana Weimershaus"},{"texte_libre":false,"auteur-lien":13031,"auteur-text":[]},{"texte_libre":false,"auteur-lien":14865,"auteur-text":[]},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Despoina Koumantou"},{"texte_libre":false,"auteur-lien":13108,"auteur-text":[]},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Peter van Endert"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Jean Davoust"},{"texte_libre":false,"auteur-lien":13178,"auteur-text":[]},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Claire Hivroz"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"David A. Gross"},{"texte_libre":false,"auteur-lien":13153,"auteur-text":[]}],"auteurs-manuel":"","liens_externes":null,"liens":[{"lien":"https:\/\/www.nature.com\/articles\/s41467-020-16471-7?utm_source=other&utm_medium=other&utm_content=null&utm_campaign=JRCN_2_LW01_CN_natureOA_article_paid_XMOL"}],"paragraphe":"

Une \u00e9tude dirig\u00e9e par L. Saveanu vient d\u2019\u00eatre publi\u00e9e dans Nature Communications<\/strong><\/p>\r\n

D\u00e9couverte de nouveaux acteurs dans l\u2019activation des Lymphocytes T<\/strong><\/p>\r\n

Dans la d\u00e9fense de l\u2019organisme contre les virus ou le d\u00e9veloppement tumoral, les lymphocytes T cytotoxiques jouent un r\u00f4le majeur. L\u2019activation des lymphocytes T requiert la reconnaissance par leur r\u00e9cepteur (TCR) des antig\u00e8nes sous forme de peptides pr\u00e9sent\u00e9s \u00e0 la surface de cellules infect\u00e9es ou de cellules tumorales. Ces peptides sont pr\u00e9sent\u00e9s par les mol\u00e9cules du complexe majeur de histocompatibilit\u00e9 de classe I (CMH-I). L\u2019interaction entre le TCR et le complexe CMH-I\/peptide antig\u00e9nique va d\u00e9clencher une cascade complexe de signalisation en aval du TCR responsable de l\u2019activation de la cellule T. La force et la dur\u00e9e de cette cascade de signalisation peuvent \u00eatre modul\u00e9es par plusieurs m\u00e9canismes, y compris l'endocytose du TCR, qui \u00e9tait jusqu\u2019ici consid\u00e9r\u00e9e comme l\u2019\u00e9tape finale de la signalisation TCR.
\r\nUne \u00e9tude collaborative entre l\u2019\u00e9quipe de Loredana Saveanu et Sophie Lotersztajn de notre centre, l\u2019Institut Curie et l\u2019Institut Necker Enfants Malades d\u00e9montre que l\u2019endocytose du TCR lui permet d\u2019y poursuivre sa signalisation. Cette signalisation endosomale semble particuli\u00e8rement importante pour les complexes CMH-I contenant des peptides de faible affinit\u00e9. Leurs travaux ont d\u00e9montr\u00e9 que la cha\u00eene CD3\u03b6 du TCR est internalis\u00e9e par un m\u00e9canisme d\u2019endocytose d\u00e9pendant de la clathrine et la dynamine 2. Une fois internalis\u00e9e, la cha\u00eene CD3\u03b6 est dirig\u00e9e vers des v\u00e9sicules intracellulaires par les prot\u00e9ines IRAP (Insulin Responsive AminoPeptidase), Syntaxine 6 (Stx6) et Rab4. Apr\u00e8s l'activation des lymphocytes T, la cha\u00eene CD3\u03b6 recrute de mol\u00e9cules de signalisation, telles que la kinase ZAP-70 au niveau des v\u00e9sicules IRAP\/ Stx6. L'inactivation du g\u00e8ne codant pour IRAP entra\u00eene une r\u00e9duction significative de la cha\u00eene CD3\u03b6 intracellulaire et de la signalisation en aval du TCR. De plus, ces d\u00e9fauts de signalisation du TCR rendent les souris invalid\u00e9es pour IRAP sp\u00e9cifiquement dans les cellules T incapables de g\u00e9n\u00e9rer une r\u00e9ponse T polyclonale anti-tumorale efficace. Ces travaux d\u00e9montrent pour la premi\u00e8re fois que le TCR est capable d\u2019engager de signaux d\u2019activation de la cellule T non seulement au niveau de la membrane plasmique, mais aussi \u00e0 partir des plateformes de signalisation endosomales. Cette nouvelle fonction du TCR orchestr\u00e9e notamment par IRAP pourrait \u00eatre exploit\u00e9e pour moduler l'activation des cellules T, en particulier dans les protocoles d\u2019immunoth\u00e9rapie \u00e0 base de cellules T.<\/p>\r\n

\"\"<\/p>\r\n

L\u00e9gende de la Figure :
\r\nRecrutement des v\u00e9sicules, identifi\u00e9es ici par le marquage d\u2019IRAP, \u00e0 la synapse immune form\u00e9e entre les cellules T et les cellules dendritiques de souris (DC). La synapse immune est visualis\u00e9e par l\u2019int\u00e9grine LFA-1.<\/p>","paragraphe_en":"

The recent work of L. Saveanu\u2019s team has been published in Nature Communications<\/strong><\/p>\r\n

New players in the activation of T Lymphocytes<\/strong><\/p>\r\n

Cytotoxic T lymphocytes play a major role in the body's defense against viruses or tumor development. Activation of T cells requires the interaction of their receptor (TCR) with the antigenic peptides presented on the surface of infected cells or tumor cells. These peptides are presented by the molecules of the major class I histocompatibility complex (MHC-I). The interaction between the TCR and the MHC-I \/ antigenic peptide complex trigger a complex signaling cascade that is responsible for the activation of the T cell. The strength and duration of this signaling cascade can be modulated by several mechanisms, including TCR endocytosis, which until now was considered to terminate the TCR signaling.<\/p>\r\n

A collaborative study between Loredana Saveanu's team and Sophie Lotersztajn from our center, the Curie Institute and the Necker Institute shows that TCR endocytosis contribute to sustained TCR signaling from endosomal platforms. This endosomal signaling seems particularly important for T cell activation by low affinity antigenic peptides.
\r\nTo join the endocytic signaling platforms, the CD3\u03b6 chain of TCR is internalized by clathrin-and dynamin- dependent endocytosis. Once internalized, the CD3\u03b6 chain is directed towards intracellular vesicles described by the protein IRAP (Insulin Responsive AminoPeptidase), Syntaxine 6 (Stx6) and Rab4. At this level, after T cell activation, the CD3\u03b6 chain recruits signaling molecules, such as the ZAP-70 kinase. IRAP deletion results in a significant reduction of the intracellular pool of CD3\u03b6 chain and an important decrease of TCR signaling cascade. In addition, mice in which IRAP was specifically deleted in T cells are unable to generate an effective polyclonal anti-tumor T response. This work demonstrates that the TCR is able to signal not only at the plasma membrane, but also from endosomal signaling platforms. This new function of TCR is orchestrated in particular by IRAP and might be relevant for modulation of T cells activation, in particular in T cell based immunotherapies.<\/p>\r\n

\"\"<\/p>\r\n

Figure legend:
\r\nRecruitment of IRAP vesicles, at the immune synapse formed between T cells and mouse dendritic cells (DC). The immune synapse is visualized by the integrin LFA-1.Une \u00e9tude dirig\u00e9e par L. Saveanu vient d\u2019\u00eatre publi\u00e9e dans Nature Communications<\/p>","documents":null},"yoast_head":"\nNew players in the activation of T Lymphocytes - CRI<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/cri1149.fr\/publication\/decouverte-de-nouveaux-acteurs-dans-lactivation-des-lymphocytes-t\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"New players in the activation of T Lymphocytes - CRI\" \/>\n<meta property=\"og:url\" content=\"https:\/\/cri1149.fr\/publication\/decouverte-de-nouveaux-acteurs-dans-lactivation-des-lymphocytes-t\/\" \/>\n<meta property=\"og:site_name\" content=\"CRI\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/CRI-Centre-de-recherche-sur-linflammation-100116118884153\" \/>\n<meta property=\"article:modified_time\" content=\"2025-09-11T14:48:01+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/cri1149.fr\/wp-content\/uploads\/2020\/06\/NCOMMS-PDF.png\" \/>\n\t<meta property=\"og:image:width\" content=\"500\" \/>\n\t<meta property=\"og:image:height\" content=\"254\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/png\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/cri1149.fr\\\/publication\\\/decouverte-de-nouveaux-acteurs-dans-lactivation-des-lymphocytes-t\\\/\",\"url\":\"https:\\\/\\\/cri1149.fr\\\/publication\\\/decouverte-de-nouveaux-acteurs-dans-lactivation-des-lymphocytes-t\\\/\",\"name\":\"New players in the activation of T Lymphocytes - 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