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Clinical and basic implications of dynamic T cell receptor clonotyping in hematopoietic cell transplantation
Simona Pagliuca, … , Betty K. Hamilton, Jaroslaw P. Maciejewski
Simona Pagliuca, … , Betty K. Hamilton, Jaroslaw P. Maciejewski
Published July 8, 2021
Citation Information: JCI Insight. ;6(13):e149080. https://doi.org/10.1172/jci.insight.149080.
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Research Article Hematology Immunology

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

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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.

Authors

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

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Figure 3

Factors influencing early and late posttransplant TCR diversity.

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Factors influencing early and late posttransplant TCR diversity.
(A) Uni...
(A) Univariable analysis of factors influencing early repertoire diversity. Forest plot indicating the odds ratio and the 95% CIs of the impact of several continuous or binary predictors on diversity (ISI day +30, considered as continuous variable). Univariable models are built either as a linear regression or logistic regression (binomial or Poisson regression as per legend). (B) Univariable analysis of factors influencing late repertoire diversity (ISI at day +180, modeling as in A). (C) Linear regressions showing the correlations between recipient (left panels) and donor (right panels) mean class I HED and diversity parameters: x axes represent the number of unique clonotypes (upper panels), and median size of pathological expansion (indicating the median number of templates per pathologically expanded clonotypes, lower panels).

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