title: Interferon-gamma differentially regulates antigen-processing functions in distinct endocytic compartments of macrophages with constitutive expression of class II major histocompatibility complex molecules.
abstract: RAW264.7 cells were transfected to express constitutively the murine class II major histocompatibility complex (MHC-II) molecule, I-Ak. The resulting RAW.Ak cells presented HEL(46-61) peptide to 3A9 T hybridoma cells, but they were unable to process and present HEL protein in their resting state. However, IFN-gamma stimulation induced the ability of RAW.Ak to process and present HEL protein, with little effect on their ability to present HEL(46-61) peptide. Antigen catabolism showed little change with IFN-gamma stimulation, suggesting that the production of peptides was not the regulated step in the processing pathway. Furthermore, HEL(46-61) peptide delivered directly into lysosomes by acid-resistant liposomes was also presented only upon IFN-gamma stimulation, while the presentation of peptides delivered into endosomes by acid-sensitive liposomes showed a lesser dependence on IFN-gamma stimulation. Thus, IFN-gamma regulated the ability of peptides delivered into certain lysosomal compartments to meet with MHC-II molecules and form peptide-MHC complexes, or to transport subsequently to the plasma membrane. Two other antigens, ribonuclease A and haemoglobin, were processed by RAW.Ak cells without IFN-gamma stimulation, suggesting that these antigens could be processed by different mechanisms, perhaps in earlier endocytic compartments. Thus, different antigens may be processed in distinct endocytic compartments, and an IFN-gamma-regulated mechanism controls the rescue of peptides from lysosomal compartments for presentation at the plasma membrane.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Hockett
authors.forename: J R
authors.initials: JR
authors.lastname: Cook
authors.forename: K
authors.initials: K
authors.lastname: Findlay
authors.forename: C V
authors.initials: CV
authors.lastname: Harding
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D002460:Cell Line; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice
chemical_list: D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma