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

Background. We have previously reported that both alpha beta and gamma delt a T cells are involved in the progression of IgA nephropathy (IgAN) to rena l failure. To determine whether the T-cells seen in the interstitium repres ent a generalized inflammatory response or whether they are proliferating o ligoclonally in response to a particular antigen, we analyzed the TCR V bet a gene usage by T cells infiltrating renal biopsies from patients with IgAN . Methods. Fourteen IgAN patients were divided by clinical criteria into stab le and progressive groups (7 in each group). Reverse transcription-polymera se chain reaction (RT-PCR) and cloning were used to characterize the expres sion of TCR V beta families in renal biopsies and in peripheral blood lymph ocytes. Results. TCR V beta 8 was significantly and preferentially expressed in mos t IgAN kidney biopsies compared with peripheral blood lymphocytes from both IgAN patients and healthy controls (P < 0.001). TCR V beta 8 expression wa s more marked in progressive biopsies than in stable biopsies (P < 0.05). S pectratyping of V beta 8 RT-PCR products from T cells infiltrating the kidn ey showed an intense spectratype band at the shortest range of amplified CD R3s in the renal biopsies of four patients. Analysis of nucleotide and dedu ced amino acid sequences of V beta 8 PCR products derived from intense spec tratype 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 re nal biopsies of all four patients examined. Conclusions. The preferential use of V beta 8 with marked similarities in t he 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 pa rticular antigen or set of antigens.