Macronutrient deprivation modulates antigen trafficking and immune recognition through HSC70 accessibility

Sarah N. Deffit, Janice S. Blum

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

B lymphocytes exploit macroautophagy to capture cytoplasmic and nuclear proteins within autophagosomes. Fusion of autopha-gosomes with lysosomes and endosomes facilitates content proteolysis, with the resulting peptides selectively binding MHC class II (MHC II) molecules, which are displayed for recognition by T lymphocytes. Nutrient deprivation or stress amplified this pathway, favoring increased MHC II presentation of cytoplasmic Ags targeted to autophagosomes. Bycontrast, this stress diminished MHC II presentation of membrane Ags including the BCR and cytoplasmic proteins that use the chaperone-mediated autophagy pathway. Whereas intracellular protease activity increased with nutrient stress, endocytic trafficking and proteolytic turnover of the BCR was impaired. Addition of macronutrients such as high molecular mass proteins restored endocytosis and Ag presentation, evidence of tightly regulated membrane trafficking dependent on macronutrient status. Altering cellular levels of the cytosolic chaperone HSC70 was sufficient to overcome the inhibitory effects of nutritional stress on BCR trafficking and Ag presentation. Together, these results reveal a key role for macronutrient sensing in regulating immune recognition and the importance of HSC70 in modulating membrane trafficking pathways during cellular stress.

Original languageEnglish (US)
Pages (from-to)1446-1453
Number of pages8
JournalJournal of Immunology
Volume194
Issue number4
DOIs
StatePublished - Feb 15 2015

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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