Conserved T cell receptor V beta CDR3 sequences in IgA nephropathy biopsies

H Wu 1, GY Zhang 1, AR Clarkson 2, JF Knight 1

1. Centre for Kidney Research, Royal Alexandra Hospital for Children, Westmead, New South Wales
2. Renal Unit, Royal Adelaide Hospital, Adelaide South Australia, Australia.

T-cell receptor (TCR) V beta gene usage by cells infiltrating renal biopsies from patients with IgAN was analysed to determine whether the T-cells seen in the interstitium represent a generalised inflammatory response or whether they are proliferating oligoclonally in response to a particular antigen. 14 IgAN patients were divided by clinical criteria into stable and progressive groups (7 in each group). RT-PCR and cloning were used to characterise expression of TCR V beta families in renal biopsies and in peripheral blood lymphocytes (PBLs). TCR V beta 8 was significantly preferentially expressed in most IgAN kidney biopsies compared with PBLs from both IgA nephropathy 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 of TCR V beta 8 at the shortest range of 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 high concordance across the CDR3 region. A conserved amino acid (leucine) at the first position of the 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. The preferential use of V beta 8 with marked similarities in the CDR3 region by some renal infiltrating T cells suggests a clonal expansion of individual 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.

Presented at the 6th International Symposium on IgA Nephropathy Leiden June 1998
Presented at the American Society of Nephrology Philadelphia October 1998

Correspondence
Dr Huiling Wu
HuilW@chw.edu.au