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 fibrillari n, a component of small nuclear ribonucleoprotein particles, and histo ne. Here, we demonstrate the activation by HgCl2 of autoreactive T cel ls specific for these nuclear proteins. Of nine CD4+ T cell hybridoma clones obtained from HgCl2-treated B10.S mice, one clone reacted to hi stone H1 and eight clones to fibrillarin. One of the fibrillarin-speci fic clones only recognized fibrillarin pretreated with HgCl2 (Hg2+ fib rillarin), suggesting that Hg2+ can induce the peresentation of a nove l fibrillarin epitope. Four fibrillarin-specific hybridoma clones stud ied for cytokine production were shown to produce interleukin (IL)-2, and three of them also produced IL-4. For stimulation of fibrillarin-s pecific T cell hybridomas, exogenous murine fibrillarin had to be adde d when antigen-presenting cells (APCs) came from untreated mice, but n ot when the APCs were obtained from HgCl2-treated animals. Apparently, HgCl2 treatment induces the presentation by APCs of a novel Hg2+ fibr illarin epitope and up-regulates the presentation of unaltered fibrill arin epitopes, thus activating 'Hg2+-specific' as well as autoreactive CD4+ T cells.