Abstract：
CD8+ T cells recognizing their cognate antigen are typically recruited as a polyclonal population consisting of multiple clonotypes with varying T-cell receptor (TCR) affinity to the target peptide-major histocompatibility complex (pMHC) complex. Advances in single-cell sequencing have increased accessibility toward identifying TCRs with matched antigens. Here we present the discovery of a monoclonal CD8+ T-cell population with specificity for a hepatitis C virus (HCV)-derived human leukocyte antigen (HLA) class I epitope (HLA-B*07:02 GPRLGVRAT) which was isolated directly ex vivo from an individual with an episode of acutely resolved HCV infection. This population was absent before infection and underwent expansion and stable maintenance for at least 2 years after infection as measured by HLA-multimer staining. Furthermore, the monoclonal clonotype was characterized by an unusually long dissociation time (half-life = 794 s and koff = 5.73 × 10-4) for its target antigen when compared with previously published results. A comparison with related populations of HCV-specific populations derived from the same individual and a second individual suggested that high-affinity TCR-pMHC interactions may be inherent to epitope identity and shape the phenotype of responses which has implications for rational TCR selection and design in the age of personalized immunotherapies.
摘要：
识别其同源抗原的CD8+T细胞通常被募集为多克隆群体,所述多克隆群体由对靶肽-主要组织相容性复合物(pMHC)复合物具有不同T细胞受体(TCR)亲和力的多种克隆型组成。单细胞测序的进展增加了鉴定具有匹配抗原的TCR的可及性。在这里，我们提出了对丙型肝炎病毒（HCV）衍生的人类白细胞抗原（HLA）I类表位（HLA-B*07：02GPRLGVRAT）具有特异性的单克隆CD8T细胞群的发现，该细胞群直接从具有急性解决的HCV感染发作的个体离体分离。如通过HLA多聚体染色所测量,该群体在感染前不存在,并且在感染后经历扩增和稳定维持至少2年。此外，与先前发表的结果相比，单克隆克隆型的特征是其靶抗原的解离时间异常长（半衰期=794s和koff=5.73×10-4）。与源自同一个体和第二个个体的HCV特异性群体的相关群体的比较表明,高亲和力TCR-pMHC相互作用可能是表位同一性固有的,并形成应答的表型,这对个性化免疫疗法时代的合理TCR选择和设计具有影响。
