Wedderburn L R, O'Hehir R E, Hewitt C R, Lamb J R, Owen M J
Imperial Cancer Research Fund, London, United Kingdom.
Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8214-8. doi: 10.1073/pnas.90.17.8214.
Sensitivity to house dust mite antigens in atopic individuals is a major cause of allergic diseases, ranging from asthma to rhinitis and dermatitis. We have studied the T-cell receptor (TCR) usage of house-dust-mite-specific CD4+ T-cell clones isolated from an atopic individual, by using the anchored polymerase chain reaction, and have analyzed the peripheral TCR repertoire of the same individual. Several T-cell clones had identified TCRs at the sequence level, despite the fact that they had been independently isolated, in some cases, in different years. These data suggest the presence in vivo of long-lived T-cell clones. We have also shown that junctional sequences identical to these clones are present in peripheral blood T cells taken 6 years after the isolation of the T-cell clones. The analysis of TCR genes used by the panel of clones reveals oligoclonality, with the variable (V) region gene segments V alpha 8 and V beta 3 being dominant, although there is minimal conservation of junctional sequences. The results have implications for understanding the TCR recognition of an environmental aeroallergen and the life span of T-cell clones in vivo during a chronic immune response.
特应性个体对屋尘螨抗原的敏感性是从哮喘到鼻炎和皮炎等过敏性疾病的主要原因。我们通过使用锚定聚合酶链反应研究了从一名特应性个体中分离出的屋尘螨特异性CD4 + T细胞克隆的T细胞受体(TCR)使用情况,并分析了该个体的外周TCR库。尽管在某些情况下,一些T细胞克隆是在不同年份独立分离的,但仍有几个T细胞克隆在序列水平上鉴定出了TCR。这些数据表明体内存在长寿T细胞克隆。我们还表明,在分离T细胞克隆6年后采集的外周血T细胞中存在与这些克隆相同的连接序列。对一组克隆所使用的TCR基因的分析揭示了寡克隆性,可变(V)区基因片段Vα8和Vβ3占主导地位,尽管连接序列的保守性极低。这些结果对于理解TCR对环境空气过敏原的识别以及慢性免疫反应期间体内T细胞克隆的寿命具有重要意义。