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The Autophagy Receptor TAX1BP1 (T6BP) improves antigen presentation by MHC-II molecules.

EMBO reports (2022-10-11)
Gabriela Sarango, Clémence Richetta, Mathias Pereira, Anita Kumari, Michael Ghosh, Lisa Bertrand, Cédric Pionneau, Morgane Le Gall, Sylvie Grégoire, Raphaël Jeger-Madiot, Elina Rosoy, Frédéric Subra, Olivier Delelis, Mathias Faure, Audrey Esclatine, Stéphanie Graff-Dubois, Stefan Stevanović, Bénédicte Manoury, Bertha Cecilia Ramirez, Arnaud Moris
RÉSUMÉ

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.

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Description du produit

Sigma-Aldrich
Anti-TAX1BP1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-CALCOCO2 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution, Ab3