Heterogeneous T cell receptor V beta gene repertoire in murine interstitial nephritis

Anti-tubular basement membrane disease (alpha TBM) produces T cell-mediated interstitial nephritis in SJL/J mice following immunization with heterologous renal tubular antigen. Initial mononuclear infiltrates appear in vivo after six to eight weeks, with subsequent progression to renal fibrosis and endstage kidney disease. Cultured lymph node derived nephritogenic T cells from these mice react to a small epitopic region of the 3M-1 target antigen and share a common amino acid motif in their V beta CDR3 regions. We now have used RT-PCR to further characterize the renal expression of T cell receptor (TcR) V beta gene repertoires during the course of this disease. Individual kidneys with focal mononuclear infiltrates characteristic of early alpha TBM disease express up to three different TcR V beta genes; however, the same V beta genes are not found in all kidneys at the same early stage of injury. DNA sequencing of the V beta RT-PCR products reveals a heterogeneous population of VDJ recombinations and deduced CDR3 amino acid sequences. Our studies do not support TcR V beta region gene restriction in histologically-detectable alpha TBM disease, but are more consistent with a dynamic, organ-specific autoimmune disease, directed at multiple autoantigenic epitopes.