The Autophagy Receptor TAX1BP1 (T6BP) is a novel player in antigen presentation by MHC-II molecules
The Autophagy Receptor TAX1BP1 (T6BP) is a novel player in antigen presentation by MHC-II molecules
Abstract 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 on the surface of antigen presenting cells (APCs) 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 mislocalization of the MHC-II-loading compartments and a rapid degradation of the invariant chain (CD74) without altering the expression and internalization kinetics of MHC-II molecules. We determined the interactome of T6BP in model APC and identified calnexin as a T6BP partner. 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.
Pereira Mathias、Sarango Gabriela、Kumari Anita、Ghosh Michael、Pionneau C¨|dric、Gr¨|goire Sylvie、Jeger-Madiot Rapha?l、Moris Arnaud、Esclatine Audrey、Richetta Cl¨|mence、Faure Mathias、Ramirez Bertha Cecilia、Rosoy Elina、Manoury B¨|n¨|dicte、Stefanovi? Stefan、Bertrand Lisa、Gall Morgane Le、Graff-Dubois St¨|phanie
Universit¨| Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC)||Sorbonne Universit¨|, INSERM, CNRS, Center for Immunology and Microbial Infections (CIMI-Paris)Universit¨| Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC)||Sorbonne Universit¨|, INSERM, CNRS, Center for Immunology and Microbial Infections (CIMI-Paris)Universit¨| Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC)||Sorbonne Universit¨|, INSERM, CNRS, Center for Immunology and Microbial Infections (CIMI-Paris)Department of Immunology, Institute for Cell Biology, University of T¨1bingenSorbonne Universit¨|, INSERM, UMS PASS, Plateforme Post-g¨|nomique de la Piti¨| Salp¨otri¨¨re (P3S)Universit¨| Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC)||Sorbonne Universit¨|, INSERM, CNRS, Center for Immunology and Microbial Infections (CIMI-Paris)Sorbonne Universit¨|, INSERM, CNRS, Center for Immunology and Microbial Infections (CIMI-Paris)Universit¨| Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC)||Sorbonne Universit¨|, INSERM, CNRS, Center for Immunology and Microbial Infections (CIMI-Paris)Universit¨| Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC)Sorbonne Universit¨|, INSERM, CNRS, Center for Immunology and Microbial Infections (CIMI-Paris)CIRI, Centre International de Recherche en Infectiologie, Universit¨| de Lyon, Inserm U1111, Universit¨| Claude Bernard Lyon 1||Equipe Labellis¨|e par la Fondation pour la Recherche M¨|dicaleUniversit¨| Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC)||Sorbonne Universit¨|, INSERM, CNRS, Center for Immunology and Microbial Infections (CIMI-Paris)Sorbonne Universit¨|, INSERM, CNRS, Center for Immunology and Microbial Infections (CIMI-Paris)Institut Necker Enfants Malades, INSERM U1151-CNRS UMR 8253, Facult¨| de m¨|decine Necker, Universit¨| de ParisDepartment of Immunology, Institute for Cell Biology, University of T¨1bingenUniversit¨| Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC)||Sorbonne Universit¨|, INSERM, CNRS, Center for Immunology and Microbial Infections (CIMI-Paris)3P5 proteom?ˉIC facility, Universit¨| de Paris, Institut CochinSorbonne Universit¨|, INSERM, CNRS, Center for Immunology and Microbial Infections (CIMI-Paris)
基础医学分子生物学
CalnexinCD4+ T cell activationInteractomeImmunopeptidomeVirus
Pereira Mathias,Sarango Gabriela,Kumari Anita,Ghosh Michael,Pionneau C¨|dric,Gr¨|goire Sylvie,Jeger-Madiot Rapha?l,Moris Arnaud,Esclatine Audrey,Richetta Cl¨|mence,Faure Mathias,Ramirez Bertha Cecilia,Rosoy Elina,Manoury B¨|n¨|dicte,Stefanovi? Stefan,Bertrand Lisa,Gall Morgane Le,Graff-Dubois St¨|phanie.The Autophagy Receptor TAX1BP1 (T6BP) is a novel player in antigen presentation by MHC-II molecules[EB/OL].(2025-03-28)[2025-04-30].https://www.biorxiv.org/content/10.1101/2021.04.21.440798.点此复制
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