Clinical T Cell Receptor Repertoire Deep Sequencing and Analysis: An Application to Monitor Immune Reconstitution Following Cord Blood Transplantation.

摘要: Spectratyping assays are well recognized as the clinical gold standard for assessing T cell receptor (TCR) repertoire in haematopoietic stem transplant (HSCT) recipients. These use length distributions of hyper variable complementarity-determining region 3 (CDR3) to characterize a patient's immune reconstitution post-transplant. However, whilst useful, TCR spectratyping is notably limited by its resolution, with technique unable provide data on individual clonotypes present sample. High-resolution clonotype necessary quantitative assessments and better understand dynamics during clinically relevant events such viral infections or GvHD. In this study we developed applied CDR3 Next Generation Sequencing (NGS) methodology assess cord blood (CBT) Using this, obtained comprehensive from 16 CBT patients 5 control samples at Great Ormond Street Hospital (GOSH). were analyzed measurement constituents post-CBT. We able both recreate quantify inferences typically drawn data. Additionally, demonstrate that an NGS approach assessment can novel insights into recovery system these patients. show be used accurately diversity valuable inference detected serially assessed progress demonstrating there dramatic variation immediately following transplantation perturbed presence findings proof concept adoption sequencing practice.