The TCR repertoire of α-synuclein-specific T cells in Parkinson's disease is surprisingly diverse.
The TCR repertoire of α-synuclein-specific T cells in Parkinson's disease is surprisingly diverse.
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DOI：
10.1038/s41598-020-79726-9
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发表时间：
2021-01-11
影响因子：
4.6
通讯作者：
Lindestam Arlehamn CS
中科院分区：
文献类型：
--
作者：
Singhania A;Pham J;Dhanwani R;Frazier A;Rezende Dutra J;Marder KS;Phillips E;Mallal S;Amara AW;Standaert DG;Sulzer D;Peters B;Sette A;Lindestam Arlehamn CS
自身抗原α-突触核蛋白（α-syn）最近被证明与帕金森病（PD）有关。在这里，我们绘制了来自6名PD患者的α-syn-specific T细胞的T细胞受体（TCR）库。将自身抗原α-syn特异性库与百日咳（PT）特异性T细胞库（作为大多数个体暴露的代表性外来抗原）进行比较，揭示α-syn库与PT库一样多样。PT特异性克隆型的多样性在PD诊断个体和年龄匹配的健康对照者之间相似。我们发现TCR库对每个PD患者都是特异性的，并且患者之间没有定义共享的TCR，这可能是由于HLA表达的差异选择了表位特异性TCR重排的不同子集。本研究提供了PD个体中α-syn-specific TCR克隆型的首次表征。抗原特异性TCR可以用作免疫治疗和诊断，以及跟踪特定T细胞的纵向变化和疾病进展的手段。
The self-antigen α-synuclein (α-syn) was recently shown to be associated with Parkinson’s disease (PD). Here we mapped the T cell receptor (TCR) repertoire of α-syn-specific T cells from six PD patients. The self-antigen α-syn-specific repertoire was compared to the repertoire of T cells specific for pertussis (PT), as a representative foreign antigen that most individuals are exposed to, revealing that the repertoire for α-syn was as diverse as the repertoire for PT. The diversity of PT-specific clonotypes was similar between individuals with PD diagnosis and age-matched healthy controls. We found that the TCR repertoire was specific to each PD patient, and no shared TCRs among patients were defined, likely due to differences in HLA expression that select for different subsets of epitope-specific TCR rearrangements. This study provides the first characterization of α-syn-specific TCR clonotypes in individuals with PD. Antigen-specific TCRs can serve as immunotherapeutics and diagnostics, and means to track longitudinal changes in specific T cells, and disease progression.
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影响因子：
56.9
作者：
Arstila, TP;Casrouge, A;Kourilsky, P
通讯作者：
Kourilsky, P
影响因子：
15.9
作者：
Antunes, Ricardo da Silva;Babor, Mariana;Sette, Alessandro
通讯作者：
Sette, Alessandro
影响因子：
32.4
作者：
Moon, James J.;Chu, H. Hamlet;Jenkins, Marc K.
通讯作者：
Jenkins, Marc K.
影响因子：
2.1
作者：
van der Walt, Stefan;Colbert, S. Chris;Varoquaux, Gael
通讯作者：
Varoquaux, Gael
影响因子：
64.8
作者：
Sulzer D;Alcalay RN;Garretti F;Cote L;Kanter E;Agin-Liebes J;Liong C;McMurtrey C;Hildebrand WH;Mao X;Dawson VL;Dawson TM;Oseroff C;Pham J;Sidney J;Dillon MB;Carpenter C;Weiskopf D;Phillips E;Mallal S;Peters B;Frazier A;Lindestam Arlehamn CS;Sette A
通讯作者：
Sette A