Quantitative Evaluation of T-Cell Repertoire Restoration Following Hematopoietic Stem Cell Transplantation in Patients with and without Graft Versus Host Disease

Xin Zhang¹Pengyi Song²Longhai Tang³Xiangjun Ji⁴Xiaohui Hu¹Xiao Ma¹Feng Chen¹Xuefeng He¹Jun Wang¹Weiyang Li¹Huiying Qiu¹Sheng-Li Xue¹Ying Wang¹MIAO MIAO¹Suning Chen¹Depei Wu¹Xiaowen Tang^1*Mingyuan Wang^3*Wenbo Wang^5*Xiaopeng Tian^1*

• ¹The First Affiliated Hospital of Soochow University, Suzhou, China
• ²Northwestern University, Evanston, United States
• ³Suzhou Blood Center, Suzhou, China
• ⁴Tongji University, Shanghai, China
• ⁵LeaLing Biopharma Co.,Ltd, Suzhou, China

Acute graft versus host disease (aGVHD) significantly contributes to mortality rates in hematopoietic stem cell transplantation (HSCT), with alloimmune T cells playing a pivotal role in its pathogenesis. This study aimed to characterize the T cell receptors (TCRs) in patients with or without aGVHD post-HSCT using a next generation sequencing approach to better understand the factors contributing to aGVHD. To achieve this aim, we defined the functional kinetics of the T cell receptor α (TRA) and T cell receptor β (TRB) clones, the changes in T-cell diversity (with identification of complementarity-determining region 3 (CDR3) sequences), and the extent of clonal expansion of certain T-cells. Our findings indicate that TCR repertoires exhibit increased diversity in patients with GVHD. This diversity decreases as aGVHD improves. The TCR clustering analysis showed that patients with aGVHD have common TCR repertoires. These findings suggest that the analysis of the TCR repertoires could be used to predict the occurrence of aGVHD and facilitate personalized approaches for the diagnosis and treatment of diseases in which T-cell activity plays a pivotal role.