title: Macronutrient deprivation modulates antigen trafficking and immune recognition through HSC70 accessibility.
abstract: B lymphocytes exploit macroautophagy to capture cytoplasmic and nuclear proteins within autophagosomes. Fusion of autophagosomes 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. By contrast, 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.
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202.
authors.forename: Sarah N
authors.initials: SN
authors.lastname: Deffit
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202 jblum@iupui.edu.
authors.forename: Janice S
authors.initials: JS
authors.lastname: Blum
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D001343:Autophagy / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D005502:Food; D050883:HSC70 Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting; D008213:Lymphocyte Activation / Q000276:immunology*; D021381:Protein Transport / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D050883:HSC70 Heat-Shock Proteins