MOLECULAR ANALYSIS OF THE HELPER T-CELL RESPONSE IN MURINE INTERSTITIAL NEPHRITIS - T-CELLS RECOGNIZING AN IMMUNODOMINANT EPITOPE USE MULTIPLE T-CELL RECEPTOR V-BETA GENES WITH SIMILARITIES ACROSS CDR3

Anti-tubular basement membrane disease (alpha TBM disease) produces T cell-mediated interstitial nephritis in SJL mice after immunization wi th renal tubular antigen. Initial mononuclear infiltrates appear in vi vo after several weeks, with the subsequent progression to renal fibro sis and end stage renal disease over many months. We have analyzed the fine specificity of the autoreactive helper T cell repertoire in alph a TBM disease through the isolation and characterization of a panel of CD4(+) Th1 clones harvested after 1-2 wk from animals immunized to pr oduce disease. All clones capable of mediating alpha TBM disease are d irected towards a 14-residue immunodominant epitope (STMSAEVPEAASEA) c ontained within the target antigen, 3M-1. Evaluation of the T cell rec eptor (TCR) V beta repertoire used by these autoreactive T cells revea ls the use of several V beta genes, but with some preference for V bet a 14. Sequencing across the putative CDR3 region of the TCR beta chain s suggests that common amino acids at the V beta(N)D beta junction and the D beta(N)J beta junction may contribute to the specific ability o f these cells to recognize the immunodominant epitope.