Ramesh Manish, Hamm David, Simchoni Noa, Cunningham-Rundles Charlotte
Montefiore Medical Center, Bronx, NY, USA.
Adaptive Biotech, Seattle, WA, USA.
Clin Immunol. 2017 May;178:1-9. doi: 10.1016/j.clim.2015.01.002. Epub 2015 Jan 14.
We used high throughput sequencing to examine the structure and composition of the T cell receptor β chain in Common Variable Immune Deficiency (CVID). TCRβ 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.
我们使用高通量测序技术来检测常见可变免疫缺陷（CVID）中T细胞受体β链的结构和组成。使用高通量多重PCR从44名成年CVID患者和22名健康成年人的基因组DNA中扩增并测序TCRβ CDR3区域。与健康对照相比，CVID患者的TCR具有显著更少的连接多样性、更少的n-核苷酸插入和缺失，并且完全缺乏在健康对照中可见的一群高度修饰的TCR（具有13个或更多V基因核苷酸缺失）。CVID患者的CDR3序列比对照DNA的克隆性显著更高，并且显示出独特的V基因使用情况。尽管连接多样性降低、克隆性增加且感染暴露相似，但与对照相比，CVID患者的DNA共享的TCR序列更少。这些异常普遍存在，存在于框外序列中，因此与选择无关，并且与特定临床并发症无关。这些数据支持CVID中存在内在的T细胞缺陷。
