Jiang Qiong, Liu Yao, Xu Baoyan, Zheng Wenhong, Xiang Xiaomei, Tang Xiaoqin, Dong Hui, Chen Yongwen, Wang Chenhui, Deng Guohong, Mao Qing, Shang Xiaoyun, Wu Yuzhang
Institute of Immunology, PLA, Third Military Medical University, Chongqing 400038, PR China.
Institute of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
Biochem Biophys Res Commun. 2018 Feb 26;497(1):153-159. doi: 10.1016/j.bbrc.2018.02.043. Epub 2018 Feb 10.
Due to their identical inheritance and shared surroundings, identical twins have been the recommended group for studying the susceptibility and prognosis of diseases. Here, CD8 T cell receptor beta (TCRβ) chains were analyzed by high-throughput sequencing in three pairs of healthy identical twins and chronic hepatitis B patients. The data showed a high level of similarity in the TCR repertoire of each pair in terms of average TCR Vβ segment expression and frequency of the complementary determining region 3 (CDR3) pattern and skewed or oligoclonal clonotypes. Notably, the level of similarity in TCR Vβ expression between the twins appeared to be independent of the consistency or inconsistency of chronic HBV infection, although the detailed CDR3 pattern and frequency were related to disease prognosis. There were more immunodominant clonotypes in patients with HBV antigen seroconversion, which showed an increased abundance. These immunodominant clonotypes may be used as favorable prognostic biomarkers and potential targets for immunotherapy. Thus, delineating the CD8 T cell repertoire of identical twins with concordant chronic viral infections provides a promising means to screen protective TCR genes for immunotherapy.
由于同卵双胞胎具有相同的遗传基因和共同的生活环境,因此一直是研究疾病易感性和预后的理想对象。在此,我们通过高通量测序分析了三对健康同卵双胞胎和慢性乙型肝炎患者的CD8 T细胞受体β(TCRβ)链。数据显示,就平均TCR Vβ区段表达、互补决定区3(CDR3)模式的频率以及偏态或寡克隆克隆型而言,每对双胞胎的TCR库具有高度相似性。值得注意的是,双胞胎之间TCR Vβ表达的相似程度似乎与慢性HBV感染的一致性或不一致性无关,尽管详细的CDR3模式和频率与疾病预后相关。HBV抗原血清学转换患者中存在更多的免疫优势克隆型,其丰度增加。这些免疫优势克隆型可作为良好的预后生物标志物和免疫治疗的潜在靶点。因此,描绘患有一致性慢性病毒感染的同卵双胞胎的CD8 T细胞库为筛选用于免疫治疗的保护性TCR基因提供了一种有前景的方法。