T cell receptor gene trans-rearrangements: chimeric gamma-delta genes in normal lymphoid tissues.
T cell receptor gene trans-rearrangements: chimeric gamma-delta genes in normal lymphoid tissues.
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DOI：
10.1126/science.2551037
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发表时间：
1989-09
期刊：
影响因子：
56.9
通讯作者：
B. Tycko;James D. Palmer;J. Sklar
中科院分区：
文献类型：
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作者：
B. Tycko;James D. Palmer;J. Sklar
在所有抗原受体基因的DNA重排过程中，V区、D区和J区基因片段的连接涉及到每个片段两侧高度保守的相同的七聚体序列的识别。为了研究这些保守序列的识别有时可能允许不同抗原受体基因之间的片段间连接的可能性，用聚合酶链式反应扩增检测了正常人淋巴组织的DNA中是否存在嵌合的γ-Delta T细胞受体基因重排。这些研究在胸腺、外周血和扁桃体中检测到V-Gamma-(D Delta)-J Delta和V Delta-(D Delta)-J Gamma重排。对胸腺RNA的分析表明，许多重排以V-(D Delta)-J Delta-C Delta和V Delta-(D Delta)-J Gamma-C Gamma转录本的形式表达。大多数转录本(所研究的20个互补DNA克隆中的19个)被适当地剪接，并在V-(D)-J连接处显示正确的开放翻译阅读框架。因此，嵌合抗原受体基因可能是由于染色体易位而在正常淋巴细胞亚群中产生的，这些基因可能有助于增加抗原受体谱系中的多样性。
Joining of V-, D-, and J-region gene segments during DNA rearrangements within all antigen receptor genes involves recognition of the same highly conserved heptamernonamer sequences flanking each segment. In order to investigate the possibility that recognition of these conserved sequences may sometimes permit intergenic joining of segments among different antigen receptor genes, DNA of normal human lymphoid tissues was examined by polymerase chain reaction amplification for the presence of chimeric gamma-delta T cell receptor gene rearrangements. These studies detected V gamma-(D delta)-J delta and V delta-(D delta)-J gamma rearrangements in thymus, peripheral blood, and tonsil. Analysis of thymus RNA indicated that many of these rearrangements are expressed as V gamma-(D delta)-J delta-C delta and V delta-(D delta)-J gamma-C gamma transcripts. Most transcripts (19 of 20 complementary DNA clones studied) are appropriately spliced and show correct open translational reading frames across the V-(D)-J junctions. Thus, chimeric antigen receptor genes are generated in a subset of normal lymphoid cells, probably as a result of chromosomal translocations, and such genes may possibly contribute to increased diversity within the antigen receptor repertoire.