Macroautophagy, endogenous MHC II loading and T cell selection: the benefits of breaking the rules

Curr Opin Immunol. 2009 Feb;21(1):92-7. doi: 10.1016/j.coi.2009.01.013. Epub 2009 Feb 24.

Abstract

Functional and biochemical assays indicate a substantial contribution of intracellularly derived peptides to the MHC class II 'ligandome'. Macroautophagy, a process traditionally known for its role in cellular housekeeping and adaptation to nutrient withdrawal, is an attractive candidate pathway for endogenous MHC class II loading. Work in cell culture systems, including antigen presentation assays, co-localization studies and sequencing of MHC class II bound peptides, demonstrates that substrates of autophagy can be loaded onto MHC class II. Advances in the development of mouse models to monitor or genetically disrupt macroautophagy now provide the basis for elucidating the immunological relevance of autophagy in vivo. Here, we will discuss recent findings suggesting a crucial role of macroautophagy in thymic epithelial cells for the generation of peptide/MHC class II ligands for positive selection and induction of T cell tolerance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigen Presentation*
  • Autophagy / genetics
  • Autophagy / immunology*
  • Autophagy-Related Protein 5
  • Epithelial Cells / cytology
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / immunology*
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Immune Tolerance / genetics
  • Mice
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / immunology
  • Molecular Chaperones / immunology
  • Molecular Chaperones / metabolism
  • Peptides / immunology
  • Peptides / metabolism
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Thymus Gland / cytology

Substances

  • Atg5 protein, mouse
  • Autophagy-Related Protein 5
  • Histocompatibility Antigens Class II
  • Microtubule-Associated Proteins
  • Molecular Chaperones
  • Peptides
  • Receptors, Antigen, T-Cell