T‐cell receptor repertoire in IgA nephropathy renal biopsies

Abstract

SUMMARY: Renal biopsies from patients with IgA nephropathy (IgAN) were studied to determine whether the presence of αβ and γδ T cells is correlated with disease progression in IgAN. the αβ and γδ T‐cell receptor (TCR) repertoire was further analysed in these renal biopsies. Immunohistochemical staining using mAb (TCRβ and TCRδ) 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 γδ T cells is associated with progressive IgAN while αβ T cells are found in both stable and progressive disease. Analysis of the TCR variable (V)β repertoire showed the preferential use of Vβ8 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 γδ T‐cell repertoire showed that γδ T cells infiltrating the kidneys of IgAN patients use a restricted subset of γδ T cells with a feature of recurrent junctional amino acid motifs in Vδ1 T cells. the results suggest that both αβ and γδ T cells are involved in the progression of IgAN to renal failure and also that there is clonal expansion of individual αβ or γδ T cells in the kidneys of some IgAN patients. the conserved amino acid in the TCR CDR3 region of Vβ8 and the feature of recurrent junctional amino acid motifs in Vδ1 T cells may indicate antigen‐driven selection.