title: Infection with Salmonella typhimurium has no effect on the composition and cleavage specificity of the 20S proteasome in human lymphoid cells.
abstract: Human leucocyte antigen (HLA)-B27 is strongly associated with spondyloarthropathies, including reactive arthritis. Several Gram-negative bacteria, such as Salmonella typhimurium, can trigger this disease. It has been suggested that peptides derived from bacterial proteins and presented by HLA-B27 to cytotoxic T lymphocytes might show molecular mimicry with autologous peptides, leading to T-cell cross-reaction and autoimmunity. Antigen presentation in Salmonella-infected cells could be modulated by changes in the composition of the proteasome, which is the major proteolytic system that generates major histocompatibility complex class I ligands. In this study we analysed whether the composition or activity of the 20S proteasome was altered upon infection of lymphoid cells by S. typhimurium. Two-dimensional gel electrophoresis failed to show any differences between the composition of 20S proteasomes from cells infected with S. typhimurium for 24 hr, relative to non-infected cells. In addition, digestions of oxidized insulin B-chain with purified 20S proteasomes from non-infected and infected cells generated the same products, indicating that the proteasomal cleavage specificity was not altered upon infection. These data indicate that infection of lymphoid cells by S. typhimurium fails to induce formation of immunoproteasomes or otherwise alter the proteolytic specificity of the 20S proteasome.
authors.affiliation: Centro de Biología Molecular Severo Ochoa (C.S.I.C.-U.A.M), Universidad Autónoma de Madrid, Facultad de Ciencias, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Marcilla
authors.forename: José Antonio López
authors.initials: JA
authors.lastname: de Castro
authors.forename: José G
authors.initials: JG
authors.lastname: Castaño
authors.forename: Iñaki
authors.initials: I
authors.lastname: Alvarez
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000276:immunology; D002478:Cells, Cultured; D015796:HLA-B27 Antigen / Q000276:immunology; D006801:Humans; D007328:Insulin / Q000276:immunology; D008221:Lymphoid Tissue / Q000201:enzymology / Q000276:immunology / Q000382:microbiology*; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000276:immunology; D046988:Proteasome Endopeptidase Complex / Q000276:immunology* / Q000378:metabolism; D012480:Salmonella Infections / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology*
chemical_list: D015796:HLA-B27 Antigen; D007328:Insulin; D010446:Peptide Fragments; D046988:Proteasome Endopeptidase Complex