LIMITED T-CELL RECEPTOR BETA-CHAIN HETEROGENEITY AMONG INTERLEUKIN-2 RECEPTOR-POSITIVE SYNOVIAL T-CELLS SUGGESTS A ROLE FOR SUPERANTIGEN IN RHEUMATOID-ARTHRITIS
LIMITED T-CELL RECEPTOR BETA-CHAIN HETEROGENEITY AMONG INTERLEUKIN-2 RECEPTOR-POSITIVE SYNOVIAL T-CELLS SUGGESTS A ROLE FOR SUPERANTIGEN IN RHEUMATOID-ARTHRITIS
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DOI：
10.1073/pnas.88.23.10921
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发表时间：
1991-12-01
影响因子：
11.1
通讯作者：
BROSTOFF, SW
中科院分区：
文献类型：
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作者：
HOWELL, MD;DIVELEY, JP;BROSTOFF, SW
类风湿性关节炎（RA）是一种影响关节滑膜的疾病，被认为是由t细胞介导的自身免疫现象引起的。负责RA发病机制的T细胞可能存在于表达白细胞介素2受体（IL-2R）的滑膜T细胞部分，IL-2R是T细胞激活的一个标志。本文报道了il - 2r阳性滑膜T细胞对T细胞受体(TCR) β链基因表达的分析。使用il - 2r特异性单克隆抗体和磁珠从未培养的滑膜组织标本中分离出这些T细胞，并使用一组人TCR β链可变区（v - β）特异性引物通过pcr催化扩增分析TCR β链转录。在这些患者样本中发现多个v - β基因家族被转录；然而，在分析的5个滑膜样本中发现了三个基因家族，v - β -3、v - β -14和v - β -17，这表明携带这些v - β -s的T细胞被选择性地保留在滑膜微环境中。在许多情况下，从单个患者扩增的v - β -3、v - β -14或v - β -17基因库以单一重排为主，表明滑膜中克隆扩增，并支持这些T细胞在RA中的作用。值得注意的是，v - β -3、v - β -14和v - β -17多肽之间的序列高度相似，特别是在第四个互补决定区（CDR）。鉴于超抗原的结合位点已被定位到TCR β链的CDR4上，携带具有显著CDR4同源性的v - β -s的T细胞滑膜定位表明，超抗原激活v - β特异性T细胞可能在RA中发挥作用。
Rheumatoid arthritis (RA) is a disease affecting the synovial membranes of articulating joints that is thought to result from T-cell-mediated autoimmune phenomena. T cells responsible for the pathogenesis of RA are likely present in that fraction of synovial T cells that expresses the interleukin 2 receptor (IL-2R), one marker of T-cell activation. We report herein an analysis of T-cell receptor (TCR) beta-chain gene expression by IL-2R-positive synovial T cells. These T cells were isolated from uncultured synovial tissue specimens by using IL-2R-specific monoclonal antibodies and magnetic beads, and TCR beta-chain transcription was analyzed by PCR-catalyzed amplification using a panel of primers specific for the human TCR beta-chain variable region (V-beta). Multiple V-beta gene families were found to be transcribed in these patient samples; however, three gene families, V-beta-3, V-beta-14, and V-beta-17, were found in a majority of the five synovial samples analyzed, suggesting that T cells bearing these V-beta-s had been selectively retained in the synovial microenvironment. In many instances, the V-beta-3, V-beta-14, or V-beta-17 repertoires amplified from an individual patient were dominated by a single rearrangement, indicative of clonal expansion in the synovium and supportive of a role for these T cells in RA. Of note is a high sequence similarity between V-beta-3, V-beta-14, and V-beta-17 polypeptides, particularly in the fourth complementarity-determining region (CDR). Given that binding sites for superantigens have been mapped to the CDR4s of TCR beta-chains, the synovial localization of T cells bearing V-beta-s with significant CDR4 homology indicates that V-beta-specific T-cell activation by superantigen may play a role in RA.