Immunosequencing identifies signatures of cytomegalovirus exposure history and HLA-mediated effects on the T cell repertoire
Immunosequencing identifies signatures of cytomegalovirus exposure history and HLA-mediated effects on the T cell repertoire
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DOI：
10.1038/ng.3822
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发表时间：
2017-05-01
期刊：
影响因子：
30.8
通讯作者：
Robins, Harlan S.
中科院分区：
文献类型：
--
作者：
Emerson, Ryan O.;DeWitt, William S.;Robins, Harlan S.
个体的T细胞库动态地编码其病原体暴露史。为了确定病原体暴露特征是否可以通过记录公共T细胞受体（TCRs）来识别，我们通过免疫测序分析了666名已知巨细胞病毒（CMV）血清状态的受试者的T细胞库。我们开发了一个统计分类框架，该框架可以在120个不同受试者的原始队列和验证队列中以高特异性和敏感性从TCRb序列目录中诊断巨细胞病毒状态。我们还证实了三个鉴定出的CMV相关的TCRb分子在体外与CMV结合，此外，我们使用这种方法准确预测了第一队列中大多数受试者的HLA-A和HLA-B等位基因。由于所有记忆T细胞反应都以体细胞TCR重组的共同格式编码，因此我们的方法可能作为一种高度并行化的诊断策略推广到各种疾病状态以及其他免疫表型。
An individual's T cell repertoire dynamically encodes their pathogen exposure history. To determine whether pathogen exposure signatures can be identified by documenting public T cell receptors (TCRs), we profiled the T cell repertoire of 666 subjects with known cytomegalovirus (CMV) serostatus by immunosequencing. We developed a statistical classification framework that could diagnose CMV status from the resulting catalog of TCRb sequences with high specificity and sensitivity in both the original cohort and a validation cohort of 120 different subjects. We also confirmed that three of the identified CMV-associated TCRb molecules bind CMV in vitro, and, moreover, we used this approach to accurately predict the HLA-A and HLA-B alleles of most subjects in the first cohort. As all memory T cell responses are encoded in the common format of somatic TCR recombination, our approach could potentially be generalized to a wide variety of disease states, as well as other immunological phenotypes, as a highly parallelizable diagnostic strategy.