T cell receptor beta germline variability is revealed by inference from repertoire data.
T cell receptor beta germline variability is revealed by inference from repertoire data.
复制标题
DOI：
10.1186/s13073-021-01008-4
复制
发表时间：
2022-01-07
期刊：
影响因子：
12.3
通讯作者：
Yaari G
中科院分区：
文献类型：
--
作者：
Omer A;Peres A;Rodriguez OL;Watson CT;Lees W;Polak P;Collins AM;Yaari G
T、B细胞受体(TCR、BCR)是获得性免疫的基础。适应性免疫受体序列分析(AIRR-SEQ)是研究免疫系统动力学的常用方法。了解影响这些曲目的组成和动态的遗传因素具有重要的科学和临床意义。由于重复的元件和未知的结构变异，编码TCRs和BCRs可变区的染色体基因座很难破译。为了应对这一挑战，最近针对B细胞开发了基于AIRR-seq的方法，使基因型和单倍型推断和发现未记录的等位基因成为可能。然而，这种方法依赖于受体可变区的完全覆盖，而大多数T细胞研究只对该区域的一小部分进行了测序。在这里，我们采用了一种B细胞管道，用于对全部和部分AIRR-seq TCR数据集进行未记录的等位基因、基因型和单倍型推断。该流水线还处理基因分配歧义，这在部分序列的数据集分析中特别重要。从全部和部分AIRR-seq TCR数据集中，我们鉴定了39个未记录的T细胞受体Beta V(TRBV)基因多态和31个未记录的5‘UTR序列。使用独立的基因组方法也观察到了这些推论的一个子集。我们发现，两个已知的T细胞受体Beta D2(TRBD2)等位基因之间的单核苷酸多态与表达谱的显著变化密切相关。我们揭示了生殖系可变性的丰富图景，并展示了单核苷酸多态如何显著影响整个谱系的组成。我们的发现为未来基础和临床研究的TCR曲目的注释提供了基础。网上版载有补充材料，可在(10.1186/s13073-021-01008-4)查阅。
T and B cell receptor (TCR, BCR) repertoires constitute the foundation of adaptive immunity. Adaptive immune receptor repertoire sequencing (AIRR-seq) is a common approach to study immune system dynamics. Understanding the genetic factors influencing the composition and dynamics of these repertoires is of major scientific and clinical importance. The chromosomal loci encoding for the variable regions of TCRs and BCRs are challenging to decipher due to repetitive elements and undocumented structural variants. To confront this challenge, AIRR-seq-based methods have recently been developed for B cells, enabling genotype and haplotype inference and discovery of undocumented alleles. However, this approach relies on complete coverage of the receptors’ variable regions, whereas most T cell studies sequence a small fraction of that region. Here, we adapted a B cell pipeline for undocumented alleles, genotype, and haplotype inference for full and partial AIRR-seq TCR data sets. The pipeline also deals with gene assignment ambiguities, which is especially important in the analysis of data sets of partial sequences. From the full and partial AIRR-seq TCR data sets, we identified 39 undocumented polymorphisms in T cell receptor Beta V (TRBV) and 31 undocumented 5 ′ UTR sequences. A subset of these inferences was also observed using independent genomic approaches. We found that a single nucleotide polymorphism differentiating between the two documented T cell receptor Beta D2 (TRBD2) alleles is strongly associated with dramatic changes in the expressed repertoire. We reveal a rich picture of germline variability and demonstrate how a single nucleotide polymorphism dramatically affects the composition of the whole repertoire. Our findings provide a basis for annotation of TCR repertoires for future basic and clinical studies. The online version contains supplementary material available at (10.1186/s13073-021-01008-4).
登录
查看更多内容
影响因子：
30.8
作者：
Emerson, Ryan O.;DeWitt, William S.;Robins, Harlan S.
通讯作者：
Robins, Harlan S.
影响因子：
8.7
作者：
Corrie BD;Marthandan N;Zimonja B;Jaglale J;Zhou Y;Barr E;Knoetze N;Breden FMW;Christley S;Scott JK;Cowell LG;Breden F
通讯作者：
Breden F
影响因子：
64.5
作者：
Birnbaum ME;Mendoza JL;Sethi DK;Dong S;Glanville J;Dobbins J;Ozkan E;Davis MM;Wucherpfennig KW;Garcia KC
通讯作者：
Garcia KC
DOI：
10.1073/pnas.1417683112
发表时间：
2015-02-24
影响因子：
11.1
作者：
Gadala-Maria, Daniel;Yaari, Gur;Kleinstein, Steven H.
通讯作者：
Kleinstein, Steven H.
影响因子：
2.2
作者：
Jackson, Katherine J. L.;Gaeta, Bruno A.;Collins, Andrew M.
通讯作者：
Collins, Andrew M.