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Clonal and constricted T cell repertoire in Common Variable Immune Deficiency

机译:克隆和收缩T细胞曲目中常见的可变免疫缺陷

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Abstract We used high throughput sequencing to examine the structure and composition of the T cell receptor ?chain in Common Variable Immune Deficiency (CVID). TCR?CDR3 regions were amplified and sequenced from genomic DNA of 44 adult CVID subjects and 22 healthy adults, using a high-throughput multiplex PCR. CVID TCRs had significantly less junctional diversity, fewer n-nucleotide insertions and deletions, and completely lacked a population of highly modified TCRs, with 13 or more V-gene nucleotide deletions, seen in healthy controls. The CVID CDR3 sequences were significantly more clonal than control DNA, and displayed unique V gene usage. Despite reduced junctional diversity, increased clonality and similar infectious exposures, DNA of CVID subjects shared fewer TCR sequences as compared to controls. These abnormalities are pervasive, found in out-of-frame sequences and thus independent of selection and were not associated with specific clinical complications. These data support an inherent T cell defect in CVID. Highlights " CVID patients have a restricted TCR repertoire with fewer mutational changes. " CVID patients lack a highly modified population of T cells seen in healthy adults. " Patients have increased clonality of their T cells irrespective of clinical history. " Despite similar repertoires, CVID patients share fewer clones compared to controls. ]]>
机译:摘要我们使用了高吞吐量测序来检查T细胞受体的结构和组成吗?链中常见的可变免疫缺乏(CVID)。使用高通量多重PCR,从44个成人CVID受试者和22例健康成人的基因组DNA扩增并测序CDR3区域。 CVID TCR具有显着较少的路径多样性,较少的N核苷酸插入和缺失,并且完全缺乏高度修饰的TCR群,具有13个或更多个V-基因核苷酸缺失,在健康对照中观察。 CVID CDR3序列明显多于对照DNA的克隆,并显示出独特的V基因使用。尽管路口分集减少,克隆态度和相似的传染性暴露,但与对照相比,CVID受试者的DNA分享了较少的TCR序列。这些异常是普遍存在的,发现在帧外序列中,因此无关,无论是否与特定的临床并发症相关。这些数据支持CVID中固有的T单元缺陷。亮点“CVID患者具有限制的TCR曲目,具有较少的突变变化。”CVID患者缺乏在健康成年人中看到的高度修饰的T细胞群。 “无论临床史如何,患者都会增加其T细胞的克隆性。”尽管有类似的曲目,但与对照组相比,CVID患者分享较少的克隆。 ]]>

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