Analysis of T cell receptor repertoire of muscle-infiltrating T lymphocytes in polymyositis. Restricted V alpha/beta rearrangements may indicate antigen-driven selection.
Analysis of T cell receptor repertoire of muscle-infiltrating T lymphocytes in polymyositis. Restricted V alpha/beta rearrangements may indicate antigen-driven selection.
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多发性肌炎肌肉浸润 T 淋巴细胞的 T 细胞受体库分析。
DOI：
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发表时间：
1993
影响因子：
15.9
通讯作者：
Lawrence Steinman
中科院分区：
文献类型：
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作者：
R. Mantegazza;F. Andreetta;P. Bernasconi;F. Baggi;Jorge R. Oksenberg;O. Simoncini;Marina Mora;Ferdinando Cornelio;Lawrence Steinman
多发性肌炎是一种以肌肉组织的单核细胞浸润为特征的炎性肌病。肌细胞毒性T淋巴细胞已被确认在浸润，但肌肉抗原，免疫攻击的目标，尚未确定。浸润性淋巴细胞上T细胞受体（TCR）可变区的分子特征有望为致病过程提供见解。通过RNA-PCR在来自15名多发性肌炎患者和16名对照（6名Duchenne肌营养不良和10名无炎性或营养不良性肌病）的肌肉活检中研究V α/β TCR库。在多发性肌炎中发现了多种重排的可变TCR基因，V α 1、V α 5、V β 1和V β 15是最常见的（存在于60-100%的患者中）。在Duchenne型肌营养不良症患者中，发现TCR V α或β重排，尽管没有观察到限制;在其他对照组的肌肉中没有发现重排。序列分析显示，在所研究的90%的V β 15克隆中存在J β 2.1区域，在多样性区域中没有随机的N添加，并且在CDR 3区域内存在共同的基序。这些结果表明，选择肌肉浸润T淋巴细胞是抗原驱动的多发性肌炎。
Polymyositis is an inflammatory myopathy characterized by mononuclear cell infiltration of muscle tissue. Myocytotoxic T lymphocytes have been recognized in the infiltrates, but the muscle antigen, target of the immune attack, has not been identified. Molecular characterization of the variable regions of T cell receptors (TCRs) on the infiltrating lymphocytes can be expected to provide insights into the pathogenic process. The V alpha/beta TCR repertoire was investigated by RNA-PCR in muscle biopsies from 15 polymyositis patients and 16 controls (6 Duchenne muscular dystrophy and 10 with no inflammatory or dystrophic myopathy). A variety of rearranged variable TCR genes was found in polymyositis, V alpha 1, V alpha 5, V beta 1, and V beta 15 being the most common (present in 60-100% of patients). In Duchenne muscular dystrophy patients TCR V alpha or beta rearrangements were found although no restriction was observed; no rearrangements were found in muscles from the other controls. Sequence analysis revealed the presence of the J beta 2.1 region in 90% of the V beta 15 clones studied, no random N additions in the diversity region, and a common motif within the CDR3 region. These results suggest that selection of muscle-infiltrating T lymphocytes is antigen driven in polymyositis.