PMID: 8977226Jan 1, 1997Paper

Highly restricted TCR-alpha beta usage by autoreactive human T cell clones specific for DNA topoisomerase I: recognition of an immunodominant epitope

The Journal of Immunology : Official Journal of the American Association of Immunologists
M KuwanaTimothy M Wright

Abstract

Autoantibody responses to DNA topoisomerase I (Topo I) are highly specific to patients with systemic sclerosis (SSc). We recently demonstrated that Topo I-specific T cells are components of the T cell repertoire of patients with SSc and healthy individuals. These autoreactive T cells were essential for the Ag-specific activation of B cells resulting in anti-Topo I Ab production in vitro and therefore are believed to play a central role in autoantibody production. To characterize the Topo I-specific T cell, 15 T cell clones reactive with Topo I were generated from two patients with SSc and three healthy donors, all of whom shared the MHC class II allele DR11. All clones expressed a CD3+CD4+CD8- phenotype and were restricted by HLA-DR. When eight rTopo I fragments were tested individually as Ags, all clones responded to F5, which encodes amino acids 209 through 386 of Topo I, but not to F10, which encodes amino acids 209 through 276, indicating that one or more immunodominant epitopes on Topo I is located between amino acids 276 and 386. Analysis of TCR gene usage showed that the predominant V(alpha) segment of the functionally rearranged TCR-alpha gene was Vdelta5, which was used by seven clones. Most strikingly, all except one ...Continue Reading

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