Molecular Analysis of the Helper T Cell Response in Murine Interstitial Nephritis: T Cells Recognizing an Immunodominant Epitope Use Multiple T Cell Receptor Vbeta Genes with Similarities across CDR3


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Abstract

Anti-tubular basement membrane disease (alphaTBM 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 alphaTBM 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 alphaTBM disease are directed towards a 14-residue immunodominant epitope (STMSAEVPEAASEA) contained within the target antigen, 3M-1. Evaluation of the T cell receptor (TCR) Vbeta repertoire used by these autoreactive T cells reveals the use of several Vbeta genes, but with some preference for Vbeta14. Sequencing across the putative CDR3 region of the TCR beta chains suggests that common amino acids at the Vbeta(N)Dbeta junction and the Dbeta(N)Jbeta junction may contribute to the specific ability of ththese cells to recognize the immunodominant epitope. (J. Clin. Invest. 1994. 94:2084-2092.) Key words: autoimmunity. autoimmune disease. kidney diseases. gene rearrangement. beta-chain. T cell antigen receptor

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