title: Mycobacterium tuberculosis inhibits MHC class II antigen processing in murine bone marrow macrophages.
abstract: Infection of murine bone-marrow-derived macrophages with viable Mycobacterium tuberculosis (MTB) H37Ra inhibited surface expression of MHC class II (MHC-II) molecules and processing of exogenous antigens for presentation to CD4(+) T hybridoma cells. The inhibition was not dependent on bacterial viability, since it was also produced by exposure to dead bacilli and MTB cytosol preparations, suggesting that it was initiated by a constitutively expressed bacterial component. Northern blot analysis demonstrated that MTB bacilli or cytosol decreased MHC-II mRNA, and immunoprecipitation of biosynthetically labeled molecules confirmed that MHC-II protein synthesis was diminished. Exposure to MTB or MTB cytosol also decreased expression of H2-DM, but H2-DM expression was still sufficient to catalyze conversion of MHC-II to SDS-stable dimers, a measure of MHC-II peptide loading. Thus, infection with MTB decreased both MHC-II and H2-DM expression, but diminished MHC-II synthesis provided the major limitation to antigen processing.
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: E H
authors.initials: EH
authors.lastname: Noss
authors.forename: C V
authors.initials: CV
authors.lastname: Harding
authors.forename: W H
authors.initials: WH
authors.lastname: Boom
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology* / Q000382:microbiology; D006681:HLA-D Antigens / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008808:Mice, Inbred CBA; D009169:Mycobacterium tuberculosis / Q000276:immunology*
chemical_list: C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D000949:Histocompatibility Antigens Class II; C111388:I-Ak antigen