{"id":64204,"date":"2023-01-26T12:12:18","date_gmt":"2023-01-26T11:12:18","guid":{"rendered":"https:\/\/cri1149.fr\/?post_type=publications&#038;p=64204"},"modified":"2025-09-11T16:47:58","modified_gmt":"2025-09-11T14:47:58","slug":"irap-dependent-endosomal-t-cell-receptor-signalling-is-essential-for-t-cell-responses","status":"publish","type":"publication","link":"https:\/\/cri1149.fr\/en\/publication\/irap-dependent-endosomal-t-cell-receptor-signalling-is-essential-for-t-cell-responses\/","title":{"rendered":"IRAP-dependent endosomal T cell receptor signalling is essential for T cell responses"},"content":{"rendered":"","protected":false},"featured_media":0,"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-64204","publication","type-publication","status-publish","hentry"],"acf":{"numero_de_publication":"Nat Commun.","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":false,"auteur-lien":16349,"auteur-text":""},{"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:\/\/pubmed.ncbi.nlm.nih.gov\/32487999\/"}],"paragraphe":"[:en]<h2 class=\"title\" style=\"text-align: justify;\">Abstract<\/h2>\r\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\r\n<p style=\"text-align: justify;\">T cell receptor (TCR) activation is modulated by mechanisms such as TCR endocytosis, which is thought to terminate TCR signalling. Here we show that, upon internalization, TCR continues to signal from a set of specialized endosomes that are crucial for T cell functions. Mechanistically, TCR ligation leads to clathrin-mediated internalization of the TCR-CD3\u03b6 complex, while maintaining CD3\u03b6 signalling, in endosomal vesicles that contain the insulin responsive aminopeptidase (IRAP) and the SNARE protein Syntaxin 6. Destabilization of this compartment through IRAP deletion enhances plasma membrane expression of the TCR-CD3\u03b6 complex, yet compromises overall CD3\u03b6 signalling; moreover, the integrity of this compartment is also crucial for T cell activation and survival after suboptimal TCR activation, as mice engineered with a T cell-specific deletion of IRAP fail to develop efficient polyclonal anti-tumour responses. Our results thus reveal a previously unappreciated function of IRAP-dependent endosomal TCR signalling in T cell activation.<\/p>\r\n<\/div>[:]","paragraphe_en":"[:en]<h2 class=\"title\" style=\"text-align: justify;\">Abstract<\/h2>\r\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\r\n<p style=\"text-align: justify;\">T cell receptor (TCR) activation is modulated by mechanisms such as TCR endocytosis, which is thought to terminate TCR signalling. Here we show that, upon internalization, TCR continues to signal from a set of specialized endosomes that are crucial for T cell functions. Mechanistically, TCR ligation leads to clathrin-mediated internalization of the TCR-CD3\u03b6 complex, while maintaining CD3\u03b6 signalling, in endosomal vesicles that contain the insulin responsive aminopeptidase (IRAP) and the SNARE protein Syntaxin 6. Destabilization of this compartment through IRAP deletion enhances plasma membrane expression of the TCR-CD3\u03b6 complex, yet compromises overall CD3\u03b6 signalling; moreover, the integrity of this compartment is also crucial for T cell activation and survival after suboptimal TCR activation, as mice engineered with a T cell-specific deletion of IRAP fail to develop efficient polyclonal anti-tumour responses. Our results thus reveal a previously unappreciated function of IRAP-dependent endosomal TCR signalling in T cell activation.<\/p>\r\n<\/div>[:]","documents":null},"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.2 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>IRAP-dependent endosomal T cell receptor signalling is essential for T cell responses - 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\/irap-dependent-endosomal-t-cell-receptor-signalling-is-essential-for-t-cell-responses\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"IRAP-dependent endosomal T cell receptor signalling is essential for T cell responses - CRI\" \/>\n<meta property=\"og:url\" content=\"https:\/\/cri1149.fr\/publication\/irap-dependent-endosomal-t-cell-receptor-signalling-is-essential-for-t-cell-responses\/\" \/>\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=\"2025-09-11T14:47:58+00:00\" \/>\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\/irap-dependent-endosomal-t-cell-receptor-signalling-is-essential-for-t-cell-responses\/\",\"url\":\"https:\/\/cri1149.fr\/publication\/irap-dependent-endosomal-t-cell-receptor-signalling-is-essential-for-t-cell-responses\/\",\"name\":\"IRAP-dependent endosomal T cell receptor signalling is essential for T cell responses - 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