title: Induction of the autoantigen proliferating cell nuclear antigen in T lymphocytes by a mycobacterial antigen.
abstract: Mycobacteria have been implicated in the pathogenesis of autoimmunity. To determine the potential effect of mycobacterial antigens on peripheral blood mononuclear cells (PBMC), we analyzed PBMC incubated with the acetone-precipitable fraction of Mycobacterium tuberculosis (APMT) for changes in cellular protein expression. Two-dimensional gel analysis showed induction of a 36-kD polypeptide identified as proliferating cell nuclear antigen (PCNA), a known autoantigen, after incubation with AP-MT. PCNA plays a role in cell proliferation and is expressed as a late growth regulated factor. However, its synthesis in response to AP-MT was induced as an early event. The early induction of PCNA was regulated at a posttranscriptional level and was restricted to T cells. Treatment of PBMC with known T cell mitogens, namely PHA, anti-CD3 antibodies, and staphylococcal superantigens failed to induce an early PCNA increase. The distinct characteristics of the AP-MT effect on PCNA expression suggest a separate mechanism of induction in response to AP-MT, compared with the late increase observed in response to mitogens. The induction of PCNA in response to mycobacterial antigens may represent a pathogenically relevant mechanism in autoimmunity.
authors.affiliation: Department of Internal Medicine, University of Michigan, Medical Center, Ann Arbor 48109.
authors.forename: H M
authors.initials: HM
authors.lastname: Haftel
authors.forename: Y
authors.initials: Y
authors.lastname: Chang
authors.forename: R
authors.initials: R
authors.lastname: Hinderer
authors.forename: S M
authors.initials: SM
authors.lastname: Hanash
authors.forename: J
authors.initials: J
authors.lastname: Holoshitz
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology*; D001324:Autoantigens / Q000096:biosynthesis*; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D016193:G1 Phase; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008934:Mitogens / Q000494:pharmacology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000942:Antigens, Bacterial; D001324:Autoantigens; D008934:Mitogens; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D003609:Dactinomycin