Ramesh Manish, Simchoni Noa, Hamm David, Cunningham-Rundles Charlotte
Montefiore Medical Center, Bronx, NY, United States.
Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Clin Immunol. 2015 Dec;161(2):190-6. doi: 10.1016/j.clim.2015.09.002. Epub 2015 Sep 7.
To examine the T cell receptor structure in the absence of B cells, the TCR β CDR3 was sequenced from DNA of 15 X-linked agammaglobulinemia (XLA) subjects and 18 male controls, using the Illumina HiSeq platform and the ImmunoSEQ analyzer. V gene usage and the V-J combinations, derived from both productive and non-productive sequences, were significantly different between XLA samples and controls. Although the CDR3 length was similar for XLA and control samples, the CDR3 region of the XLA T cell receptor contained significantly fewer deletions and insertions in V, D, and J gene segments, differences intrinsic to the V(D)J recombination process and not due to peripheral T cell selection. XLA CDR3s demonstrated fewer charged amino acid residues, more sharing of CDR3 sequences, and almost completely lacked a population of highly modified Vβ gene segments found in control DNA, suggesting both a skewed and contracted T cell repertoire in XLA.
为了在没有B细胞的情况下检测T细胞受体结构，使用Illumina HiSeq平台和ImmunoSEQ分析仪，对15名X连锁无丙种球蛋白血症（XLA）患者和18名男性对照的DNA进行TCRβ互补决定区3（CDR3）测序。来自有功能和无功能序列的V基因使用情况以及V-J组合在XLA样本和对照之间存在显著差异。尽管XLA样本和对照样本的CDR3长度相似，但XLA T细胞受体的CDR3区域在V、D和J基因片段中所含的缺失和插入显著较少，这些差异是V(D)J重组过程所固有的，而非外周T细胞选择所致。XLA的CDR3显示出带电荷氨基酸残基较少、CDR3序列共享较多，并且几乎完全缺乏对照DNA中发现的高度修饰的Vβ基因片段群体，这表明XLA中T细胞库存在偏斜和收缩。
