Institute of Immunology, PLA, Third Military Medical University, Chongqing, P. R. China.
Department of Health, Third Military Medical University, Chongqing, P. R. China.
Eur J Immunol. 2018 Sep;48(9):1539-1549. doi: 10.1002/eji.201747327. Epub 2018 Jul 16.
The presence of shared T-cell clonotypes was found in several different diseases, but its relationship with the progression of disease remains unclear. By sequencing the complementary determining region 3 of T-cell receptor (TCR) β chains from the purified antigen-experienced CD8 T cells, we characterized the T-cell repertoire in a prospective cohort study among 75 patients with chronic hepatitis B in China, as well as a healthy control and a validation cohort. We found that most T-cell clones from patients harbored the "patient-specific" TCR sequences. However, "patient-shared" TCR clonotypes were also widely found, which correlated with the favorable turnover of disease. Interestingly, the frequency of the "patient-shared" clonotypes can serve as a biomarker for favorable prognosis. Based on the clonotypes in those patients with favorable outcomes, we created a database including several clusters of protective anti-HBV CD8 T-cell clonotypes that might be a reasonable target for therapeutic vaccine development or adoptive cell transfer therapy. These findings were validated in an additional independent cohort of patients. These results suggest that the "patient-shared" TCR clonotypes may serve as a valuable prognostic tool in the treatment of chronic hepatitis B and possibly other chronic viral diseases.
在多种不同疾病中发现了共享 T 细胞克隆型的存在，但它与疾病进展的关系尚不清楚。通过对来自中国 75 例慢性乙型肝炎患者、健康对照者和验证队列中经纯化的抗原经历的 CD8 T 细胞的 T 细胞受体 (TCR)β 链互补决定区 3 进行测序，我们对 T 细胞库进行了前瞻性队列研究。我们发现，大多数来自患者的 T 细胞克隆具有“患者特异性”TCR 序列。然而，也广泛存在“患者共享”TCR 克隆型，这与疾病的良好转归相关。有趣的是，“患者共享”克隆型的频率可作为预后良好的生物标志物。基于那些预后良好的患者的克隆型，我们创建了一个数据库，其中包括几个保护性抗乙型肝炎病毒 CD8 T 细胞克隆型簇，这些簇可能是治疗性疫苗开发或过继细胞转移治疗的合理靶标。这些发现在另外一个独立的患者队列中得到了验证。这些结果表明，“患者共享”TCR 克隆型可能成为慢性乙型肝炎治疗中一种有价值的预后工具，并可能对其他慢性病毒病也有价值。
