Mercuric-chloride-induced autoimmunity in mice involves up-regulated presentation by spleen cells of altered and unaltered nucleolar self antigen.
HgCl2 treatment of B10.S mice induces IgG autoantibodies to fibrillarin, a component of small nuclear ribonucleoprotein particles, and histone. Here, we demonstrate the activation by HgCl2 of autoreactive T cells specific for these nuclear proteins. Of nine CD4+ T cell hybridoma clones obtained from HgCl2-treated B10.S mice, one clone reacted to histone Hl and eight clones to fibrillarin. One of the fibrillarin-specific clones only recognized fibrillarin pretreated with HgCl2 (Hg2+ fibrillarin), suggesting that Hg2+ can induce the presentation of a novel fibrillarin epitope. Four fibrillarin-specific hybridoma clones studied for cytokine production were shown to produce interleukin (IL)-2, and three of them also produced IL-4. For stimulation of fibrillarin-specific T cell hybridomas, exogenous murine fibrillarin had to be added when antigen-presenting cells (APCs) came from untreated mice, but not when the APCs were obtained from HgCl2-treated animals. Apparently, HgCl2 treatment induces the presentation by APCs of a novel Hg2+ fibrillarin epitope and up-regulates the presentation of unaltered fibrillarin epitopes, thus activating 'Hg(2+)-specific' as well as autoreactive CD4+ T cells.
Kubicka-Muranyi
M
M
Division of Immunology, University Düsseldorf, Germany.
Griem
P
P
Lübben
B
B
Rottmann
N
N
Lührmann
R
R
Gleichmann
E
E
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000139:chemically induced; D015551:Autoimmunity / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002868:Chromosomal Proteins, Non-Histone / Q000276:immunology / Q000378:metabolism; D002999:Clone Cells; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006657:Histones / Q000276:immunology; D006825:Hybridomas; D008627:Mercuric Chloride / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D011485:Protein Binding / Q000276:immunology; D012261:Ribonucleoproteins / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D015854:Up-Regulation / Q000276:immunology
D001324:Autoantigens; D002868:Chromosomal Proteins, Non-Histone; D000949:Histocompatibility Antigens Class II; D006657:Histones; D012261:Ribonucleoproteins; C047458:fibrillarin; D008627:Mercuric Chloride