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.

Abstract

Anti-tubular basement membrane disease (aTBM 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

Molecular identification of T cells that respond in a primary bulk culture to a peptide derived from a platelet glycoprotein implicated in neonatal alloimmune thrombocytopenia.

“…There are numerous examples where a class II MHC restricted response shows this characteristic for the BV or AV chains (25)(26)(27)(28)(29)(30)(31)(32). Finding a CDR3 motif associated with two different BV genes in the same animal or individual is much less common (33). However, in vitro mutagenesis has shown that for moth cytochrome c peptide, the transfer of a CDR3 onto an unrelated BV gene reconstituted partial recognition (34).…”

Revisiting Tolerance Induced by Autoantigen in Incomplete Freund’s Adjuvant

“…In an effort to address these issues, we revisited three models of EAE (mediated by injections of MBP, PLP, and MOG, respectively) and a related model of murine interstitial nephritis, antitubular basement membrane (␣TBM) disease (47)(48)(49). Like EAE, ␣TBM disease is elicited by immunization with a tissue-specific autoantigen (renal tubular Ag, RTA) in CFA, and injection of RTA with IFA has been reported to prevent the disease (50).…”

“…RTA and MBP were prepared in our laboratory, as described (47,54). The nonglycosylated recombinant protein corresponding to the extracellular domain of rat MOG (aa 1-125) was expressed in the Escherichia coli strain DH5-␣ and purified to homogeneity, as previously described (55).…”

“…Disease scores for interstitial nephritis were defined as follows. Grade 0, normal kidney; grade 0.5, rare focal mononuclear cell infiltration; grade 1, mononuclear cell infiltration of the interstitium of Ͻ10% of the renal cortex; grade 2, mononuclear cell infiltration of the interstitium of Ͼ10% Ͻ50% of the renal cortex; grade 3, mononuclear cell infiltration of the interstitium of Ͼ50% of the renal cortex with tubular drop-out and interstitial fibrosis (47,48). Standard histologic scoring of brain inflammation in EAE was used (23,34).…”

The Downside of a Drug-Crazed World

“…Whether the T cell clones were truly oligoclonal cannot be determined without cDNA sequencing a good number of CDR3 regions that form part the V␤ chain of their antigen-specific T cell receptors (11,12). The CDR3 region of the V␤ chain is fashioned by VDJ recombination and an oligoclonal response should express only a limited number of recombination events.…”