IgA肾病活检中保守的T细胞受体β链互补决定区3序列。

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

作者信息

Wu H, Zhang G Y, Clarkson A R, Knight J F

机构信息

Center for Kidney Research, Royal Alexandra Hospital for Children, Westmead, New South Wales, and Renal Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.

出版信息

Kidney Int. 1999 Jan;55(1):109-19. doi: 10.1046/j.1523-1755.1999.00243.x.

DOI:10.1046/j.1523-1755.1999.00243.x

PMID:9893119

Abstract

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 Vbeta 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 Vbeta families in renal biopsies and in peripheral blood lymphocytes.

RESULTS

TCR Vbeta8 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 Vbeta8 expression was more marked in progressive biopsies than in stable biopsies (P < 0.05). Spectratyping of Vbeta8 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 Vbeta8 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 Vbeta8 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 Vbeta8 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.

摘要

背景

我们之前报道过，αβ和γδ T细胞均参与IgA肾病（IgAN）进展至肾衰竭的过程。为了确定间质中所见的T细胞是代表一种全身性炎症反应，还是它们针对特定抗原进行寡克隆增殖，我们分析了来自IgAN患者肾活检组织中浸润T细胞的TCR Vβ基因使用情况。

方法

根据临床标准将14例IgAN患者分为稳定组和进展组（每组7例）。采用逆转录-聚合酶链反应（RT-PCR）和克隆技术来表征肾活检组织和外周血淋巴细胞中TCR Vβ家族的表达。

结果

与IgAN患者和健康对照的外周血淋巴细胞相比，TCR Vβ8在大多数IgAN肾活检组织中显著且优先表达（P < 0.001）。TCR Vβ8在进展性活检组织中的表达比稳定活检组织中更明显（P < 0.05）。对浸润肾脏的T细胞的Vβ8 RT-PCR产物进行谱型分析，在4例患者的肾活检组织中，扩增的CDR3最短范围内出现了一条强烈的谱型带。对来自这些肾活检组织中强烈谱型带的Vβ8 PCR产物的核苷酸和推导氨基酸序列分析显示，整个CDR3区域具有高度一致性。在所有4例接受检查患者的肾活检组织获得的多个序列中，发现Vβ8非种系编码核苷酸和多样性（ND）连接点第一位的保守氨基酸（亮氨酸）出现频率为95%。