The Autophagy Receptor TAX1BP1 ( T6BP ) improves antigen presentation by MHC‐II molecules - Archive ouverte HAL Access content directly
Journal Articles EMBO Reports Year : 2022

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

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Michael Ghosh
Stefan Stevanović
Bénédicte Manoury

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 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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Dates and versions

hal-03864670 , version 1 (21-11-2022)

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Gabriela Sarango, Clémence Richetta, Mathias Pereira, Anita Kumari, Michael Ghosh, et al.. The Autophagy Receptor TAX1BP1 ( T6BP ) improves antigen presentation by MHC‐II molecules. EMBO Reports, 2022, ⟨10.15252/embr.202255470⟩. ⟨hal-03864670⟩
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