[HTML][HTML] Clinical and basic implications of dynamic T cell receptor clonotyping in hematopoietic cell transplantation

S Pagliuca, C Gurnari, S Hong, R Zhao… - JCI insight, 2021 - ncbi.nlm.nih.gov
S Pagliuca, C Gurnari, S Hong, R Zhao, S Kongkiatkamon, L Terkawi, M Zawit, Y Guan
JCI insight, 2021ncbi.nlm.nih.gov
TCR repertoire diversification constitutes a foundation for successful immune reconstitution
after allogeneic hematopoietic cell transplantation (allo-HCT). Deep TCR Vβ sequencing of
135 serial specimens from a cohort of 35 allo-HCT recipients/donors was performed to
dissect posttransplant TCR architecture and dynamics. Paired analysis of clonotypic
repertoires showed a minimal overlap with donor expansions. Rarefied and hyperexpanded
clonotypic patterns were hallmarks of T cell reconstitution and influenced clinical outcomes …
Abstract
TCR repertoire diversification constitutes a foundation for successful immune reconstitution after allogeneic hematopoietic cell transplantation (allo-HCT). Deep TCR Vβ sequencing of 135 serial specimens from a cohort of 35 allo-HCT recipients/donors was performed to dissect posttransplant TCR architecture and dynamics. Paired analysis of clonotypic repertoires showed a minimal overlap with donor expansions. Rarefied and hyperexpanded clonotypic patterns were hallmarks of T cell reconstitution and influenced clinical outcomes. Donor and pretransplant TCR diversity as well as divergence of class I human leukocyte antigen genotypes were major predictors of recipient TCR repertoire recovery. Complementary determining region 3–based specificity spectrum analysis indicated a predominant expansion of pathogen-and tumor-associated clonotypes in the late post–allo-HCT phase, while autoreactive clones were more expanded in the case of graft-versus-host disease occurrence. These findings shed light on post–allo-HCT adaptive immune reconstitution processes and possibly help in tracking alloreactive responses.
ncbi.nlm.nih.gov