%0 Journal Article %T The Autophagy Receptor TAX1BP1 ( T6BP ) improves antigen presentation by MHC‐II molecules %+ Institut de Biologie Intégrative de la Cellule (I2BC) %+ Centre d'Immunologie et des Maladies Infectieuses (CIMI) %+ Laboratoire de biologie et pharmacologie appliquée (LBPA) %+ University of Tübingen %+ Plateforme Post-génomique de la Pitié-Salpêtrière (PASS-P3S) %+ Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS) %+ Plateforme protéomique 3P5 [Institut Cochin] (3P5) %+ Centre International de Recherche en Infectiologie (CIRI) %+ Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)) %A Sarango, Gabriela %A Richetta, Clémence %A Pereira, Mathias %A Kumari, Anita %A Ghosh, Michael %A Bertrand, Lisa %A Pionneau, Cédric %A Le Gall, Morgane %A Grégoire, Sylvie %A Jeger-Madiot, Raphaël %A Rosoy, Elina %A Subra, Frédéric %A Delelis, Olivier %A Faure, Mathias %A Esclatine, Audrey %A Graff‐dubois, Stéphanie %A Stevanović, Stefan %A Manoury, Bénédicte %A Ramirez, Bertha Cecilia %A Moris, Arnaud %< avec comité de lecture %@ 1469-221X %J EMBO Reports %I EMBO Press %8 2022-10-10 %D 2022 %R 10.15252/embr.202255470 %M 36215666 %K calnexin %K CD4 + T cell activation %K interactome %K immunopeptidome %K virus Subject Categories Autophagy & Cell Death %K Immunology %K Signal Transduction %K calnexin %K calnexin %K calnexin %Z Life Sciences [q-bio]Journal articles %X CD4 + T lymphocytes play a major role in the establishment and maintenance of immunity. They are activated by antigenic peptides derived from extracellular or newly synthesized (endogenous) proteins presented by the MHC-II molecules. The pathways leading to endogenous MHC-II presentation remain poorly characterized. We demonstrate here that the autophagy receptor, T6BP, influences both autophagy-dependent and-independent endogenous presentation of HIV-and HCMV-derived peptides. By studying the immunopeptidome of MHC-II molecules, we show that T6BP affects both the quantity and quality of peptides presented. T6BP silencing induces the mislocalization of the MHC-II-loading compartments and rapid degradation of the invariant chain (CD74) without altering the expression and internalization kinetics of MHC-II molecules. Defining the interactome of T6BP, we identify calnexin as a T6BP partner. We show that the calnexin cytosolic tail is required for this interaction. Remarkably, calnexin silencing replicates the functional consequences of T6BP silencing: decreased CD4 + T cell activation and exacerbated CD74 degradation. Altogether, we unravel T6BP as a key player of the MHC-II-restricted endogenous presentation pathway, and we propose one potential mechanism of action. %G English %2 https://hal.science/hal-03864670/document %2 https://hal.science/hal-03864670/file/embr.202255470.pdf %L hal-03864670 %U https://hal.science/hal-03864670 %~ INSERM %~ ENS-LYON %~ CEA %~ CNRS %~ UNIV-LYON1 %~ ENS-CACHAN %~ CIMI %~ CEA-UPSAY %~ I2BC %~ UNIV-PARIS-SACLAY %~ OMIQUE %~ JOLIOT %~ CEA-DRF %~ CIRI %~ SORBONNE-UNIVERSITE %~ SORBONNE-UNIV %~ SU-MEDECINE %~ SU-SCIENCES %~ UDL %~ UNIV-LYON %~ UNIV-PARIS %~ UNIVERSITE-PARIS %~ UP-SANTE %~ PASS %~ PASS-P3S %~ UNIVERSITE-PARIS-SACLAY %~ SU-TI %~ ENS-PARIS-SACLAY %~ GS-BIOSPHERA %~ GS-LIFE-SCIENCES-HEALTH %~ GS-HEALTH-DRUG-SCIENCES %~ ALLIANCE-SU %~ PASS_PROTEOMIC