Molecular analysis of the helper T cell response in murine interstitial nephritis. T cells recognizing an immunodominant epitope use multiple T cell receptor Vβ genes with similarities across CDR3

Peter S. Heeger, William E. Smoyer, Theodore Saad, Shelley Albert, Carolyn J. Kelly, Eric G. Neilson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Anti-tubular basement membrane disease (αTBM disease) produces T cell- mediated interstitial nephritis in SJL mice after immunization with renal tubular antigen. Initial mononuclear infiltrates appear in vivo after several weeks, with the subsequent progression to renal fibrosis and end stage renal disease over many months. We have analyzed the fine specificity of the autoreactive helper T cell repertoire in αTBM disease through the isolation and characterization of a panel of CD4+ Th1 clones harvested after 1-2 wk from animals immunized to produce disease. All clones capable of mediating αTBM disease are directed towards a 14-residue immunodominant epitope (STMSAEVPEAASEA) contained within the target antigen, 3M-1. Evaluation of the T cell receptor (TCR) Vβ repertoire used by these autoreactive T cells reveals the use of several Vβ genes, but with some preference for Vβ14. Sequencing across the putative CDR3 region of the TCR β chains suggests that common amino acids at the Vβ(N)Dβ junction and the Dβ(N)Jβ junction may contribute to the specific ability of these cells to recognize the immunodominant epitope.

Original languageEnglish (US)
Pages (from-to)2084-2092
Number of pages9
JournalJournal of Clinical Investigation
Volume94
Issue number5
DOIs
StatePublished - 1994

Keywords

  • T cell antigen receptor
  • autoimmune disease
  • autoimmunity
  • gene rearrangement
  • kidney diseases
  • β- chain

ASJC Scopus subject areas

  • Medicine(all)

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