T-cell receptor repertoire in IgA nephropathy renal biopsies

Renal biopsies from patients with IgA nephropathy (IgAN) were studied to determine whether the presence of alphabeta and gammadelta T cells is correlated with disease progression in IgAN. The alphabeta and gammadelta T-cell receptor (TCR) repertoire was further analysed in these renal biopsies. Immunohistochemical staining using mAb (TCRbeta and TCRdelta) and molecular studies using reverse transcription-polymerase chain reaction (RT-PCR) with primers specific for TCR families were undertaken. CDR3 length spectratyping and sequencing of TCR chains were used to analyse the diversity of the CDR3 region of these receptors. It was demonstrated that the presence of gammadelta T cells is associated with progressive IgAN while alphabeta T cells are found in both stable and progressive disease. Analysis of the TCR variable (V)beta repertoire showed the preferential use of Vbeta8 with marked similarities in the CDR3 region by some renal infiltrating T cells in the kidney of some IgAN patients, although T cells infiltrating the renal interstitium of patients with IgAN express heterogeneous T cell receptors. The data from analysis of gammadelta T-cell repertoire showed that gammadelta T cells infiltrating the kidneys of IgAN patients use a restricted subset of gammadelta T cells with a feature of recurrent junctional amino acid motifs in Vdelta1 T cells. The results suggest that both alphabeta and gammadelta T cells are involved in the progression of IgAN to renal failure and also that there is clonal expansion of individual alphabeta or gammadelta T cells in the kidneys of some IgAN patients. The conserved amino acid in the TCR CDR3 region of Vbeta8 and the feature of recurrent junctional amino acid motifs in Vdelta1 T cells may indicate antigen-driven selection.