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Kubicka-Muranyi M, Griem P, Lubben B, Rottmann N, Luhrmann R, Gleichmann E: Mercuric-chloride-induced autoimmunity in mice involves up-regulated presentation by spleen cells of altered and unaltered nucleolar self antigen. Int Arch Allergy Immunol. 1995 Sep;108(1):1-10. 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. |
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