Induction of the autoantigen proliferating cell nuclear antigen in T lymphocytes by a mycobacterial antigen.
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.
Haftel
H M
HM
Department of Internal Medicine, University of Michigan, Medical Center, Ann Arbor 48109.
Chang
Y
Y
Hinderer
R
R
Hanash
S M
SM
Holoshitz
J
J
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
D000942:Antigens, Bacterial; D001324:Autoantigens; D008934:Mitogens; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D003609:Dactinomycin