Conserved T-cell receptor β chain CDR3 sequences in IgA nephropathy biopsies

Background. We have previously reported that both alpha beta and gamma delta T cells are involved in the progression of IgA nephropathy (IgAN) to renal failure. To determine whether the T-cells seen in the interstitium represent a generalized inflammatory response or whether they are proliferating oligoclonally in response to a particular antigen, we analyzed the TCR V beta gene usage by T cells infiltrating renal biopsies from patients with IgAN. Methods. Fourteen IgAN patients were divided by clinical criteria into stable and progressive groups (7 in each group). Reverse transcription-polymerase chain reaction (RT-PCR) and cloning were used to characterize the expression of TCR V beta families in renal biopsies and in peripheral blood lymphocytes. Results. TCR V beta 8 was significantly and preferentially expressed in most IgAN kidney biopsies compared with peripheral blood lymphocytes from both IgAN patients and healthy controls (P < 0.001). TCR V beta 8 expression was more marked in progressive biopsies than in stable biopsies (P < 0.05). Spectratyping of V beta 8 RT-PCR products from T cells infiltrating the kidney showed an intense spectratype band at the shortest range of amplified CDR3s in the renal biopsies of four patients. Analysis of nucleotide and deduced amino acid sequences of V beta 8 PCR products derived from intense spectratype bands from these renal biopsies revealed a high concordance across the CDR3 region. A conserved amino acid (leucine) at the first position of the nongermline-encoded nucleotides and diversity (ND) junction of V beta 8 was found at a frequency of 95% in multiple sequences obtained from the renal biopsies of all four patients examined. Conclusions. The preferential use of V beta 8 with marked similarities in the CDR3 region by some renal infiltrating T cells suggests clonal expansion of T cells in the kidneys of some IgAN patients. Conserved amino acids in the TCR CDR3 hypervariable region may contribute to the recognition of a particular antigen or set of antigens.