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

Gabriela Sarango1,2, Clémence Richetta2,3, Mathias Pereira1,2

  • 1Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Gif-sur-Yvette, France.

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Summary

The autophagy receptor T6BP is crucial for endogenous peptide presentation via MHC-II molecules, impacting CD4+ T cell activation. This study reveals T6BP

Keywords:
CD4+ T cell activationcalnexinimmunopeptidomeinteractomevirus

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Area of Science:

  • Immunology
  • Molecular Biology
  • Cellular Biology

Background:

  • CD4+ T lymphocytes are vital for adaptive immunity, requiring peptide presentation by MHC-II molecules.
  • Endogenous peptide presentation via MHC-II is essential but not fully understood.
  • Antigen presentation pathways critically influence immune responses.

Purpose of the Study:

  • To investigate the role of the autophagy receptor T6BP in endogenous MHC-II peptide presentation.
  • To elucidate the molecular mechanisms by which T6BP regulates MHC-II presentation.
  • To identify T6BP-interacting proteins involved in the MHC-II pathway.

Main Methods:

  • Immunopeptidome analysis of MHC-II molecules.
  • T6BP and calnexin silencing experiments.
  • Analysis of MHC-II loading compartments and invariant chain (CD74) degradation.
  • T6BP interactome studies.

Main Results:

  • T6BP influences both autophagy-dependent and -independent endogenous peptide presentation.
  • T6BP silencing alters peptide quantity and quality presented by MHC-II.
  • T6BP silencing leads to mislocalization of MHC-II loading compartments and CD74 degradation.
  • Calnexin is identified as a T6BP partner, and its silencing mimics T6BP silencing effects.
  • Reduced CD4+ T cell activation observed upon T6BP or calnexin silencing.

Conclusions:

  • T6BP is a key regulator of the MHC-II-restricted endogenous presentation pathway.
  • T6BP interacts with calnexin to modulate MHC-II presentation and CD4+ T cell responses.
  • Understanding T6BP function provides insights into immune regulation and potential therapeutic targets.