학술논문
Clinical and basic implications of dynamic T cell receptor clonotyping in hematopoietic cell transplantation
Document Type
article
Author
Simona Pagliuca; Carmelo Gurnari; Sanghee Hong; Ran Zhao; Sunisa Kongkiatkamon; Laila Terkawi; Misam Zawit; Yihong Guan; Hassan Awada; Ashwin Kishtagari; Cassandra M. Kerr; Thomas LaFramboise; Bhumika J. Patel; Babal K. Jha; Hetty E. Carraway; Valeria Visconte; Navneet S. Majhail; Betty K. Hamilton; Jaroslaw P. Maciejewski
Source
JCI Insight, Vol 6, Iss 13 (2021)
Subject
Language
English
ISSN
2379-3708
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.